Chemical composition of the CG clay and steel slag (% in weight). The slag predominantly is formed by composites of Ca, Al, Fe, Mg and Si
\r\n\tBasic science studies have provided new insights into the pathophysiology of β-thalassemia. Studies of genotypic and phenotypic heterogeneity among patients and a better understanding of the control of erythropoiesis have provided new targets for designing novel agents that can be tailored to individual patient needs. JAK-2 kinase inhibitors and agents targeting the GDF-11/SMAD pathway are in clinical trials.
\r\n\r\n\tThis book will attempt to discuss the historical background of the disease and present the most up-to-date material regarding disease management in today's world for the reader to be updated on the best practice management of the disease.
",isbn:"978-1-83969-158-4",printIsbn:"978-1-83969-157-7",pdfIsbn:"978-1-83969-159-1",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,hash:"23abb2fecebc48a2df8a954eb8378930",bookSignature:"Dr. Akshat Jain",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/10727.jpg",keywords:"History of Gene Mutation, Genetic Counselling, Anemia, Genotyping, Hemoglobin Electrophoresis, HLA typing, Hemolysis, Aplastic Anemia, Blood Transfusion, Laboratory Testing, Fetal Hemoglobin Modifiers, Gene Therapy",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"February 4th 2021",dateEndSecondStepPublish:"March 4th 2021",dateEndThirdStepPublish:"May 3rd 2021",dateEndFourthStepPublish:"July 22nd 2021",dateEndFifthStepPublish:"September 20th 2021",remainingDaysToSecondStep:"a month",secondStepPassed:!0,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"A board-certified pediatrician with a specialization in pediatric hematology-oncology and stem cell transplantation. In collaboration with Harvard Medical School, he studied and reported the outcomes of a global hemophilia collaboration. He is a member of the American Board of Pediatrics, Hematology, and American Board of Pediatrics, also he is a Committee member for the American Society of Pediatric Hematology-Oncology Special Interest Group in Global Pediatric Hematology oncology.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"344600",title:"Prof.",name:"Akshat",middleName:null,surname:"Jain",slug:"akshat-jain",fullName:"Akshat Jain",profilePictureURL:"https://mts.intechopen.com/storage/users/344600/images/system/344600.jpg",biography:"Akshat Jain M.D. M.P.H.\n11175 Campus Street \nLoma Linda, California 92354\nPhone: (917) 331-3216\nakshatjainusa@gmail.com \n\nMEDICAL EDUCATION \n●\tS.S.R. Medical College, Belle Rive, Mauritius - MBBS, Bachelor of Medicine Bachelor of Surgery, 2007\n●\tPediatrics Residency Training ,The New York Medical College, Metropolitan Hospital , Dec2008-Dec 2011\n●\tPediatric Hematology Oncology and Stem Cell Transplant Fellowship, Cohen’s Children's Hospital of New York at LIJ-North Shore Health system. July 2012- September 2015\n●\tMaster’s in Public Health ,Hofstra University School of Public Health ,New York , August 2015\n\n\nHONORS/ AWARDS \n●\tThe New York Academy of Medicine Honorary Associate Award , December 2009\n●\tProgram Leadership Award - Committee of Interns and Residents (C.I.R./SIEU), April 2010\n●\tAmerican Academy of Pediatrics Program Delegate Award, New York Medical College, December 2010.\n●\tCitation of Honor from New York County for Excellence in Medicine and Service to Long Island, New York,Nassau county executive chambers , August 15,2015 \n●\tTimes of India N.R.I. ( Non Resident Achiever ) award , August 2015 \n●\tCertificate for academic excellence –Hofstra University School of Health Science & Human Services, New York August 26, 2015\n●\tAmerican Society of Hematology Leadership Institute Award , April 2016\n●\tGlobal Health Speaker Award , convener of Global Health Symposium, Hofstra NorthWell School of Medicine and School of Public health , May 2016\n●\tInternational Pediatric Lymphoma Meeting ,Session Chairperson of Pediatric Lymphoma , Indian Society of Hematology and Oncology , November 2016\n●\tContent Leader Award for Hematology perspective’s in the Global CoronaVirus Pandemic Preparedness Response for Medical Association of physicians of Indian Origin, April 2020.\n●\tConvener and Chairperson International Webinar for COVID 19 Coagulopathy, May 2020. \n●\tFeatured in the Top Doctors magazine 2020, ranked top pediatric Hematologist Oncologist for Southern California.\n\nNATIONAL/INTERNATIONAL POSITIONS \n●\tHofstra University Dean Advisory Board for the School of Health Professions, December 2017\n●\tEditorial Board – American Society of Pediatric Hematology Oncology Communications Committee, International Journal of Hematology Research (ISSN 2409-3548)\n●\tReviewer - JAMA Pediatrics (ISSN: 2168-6203), British Medical Journal (ISSN, 1468-5833), JAMA Oncology (ISSN: 2374-2437), International Journal of Hematology Research (ISSN 2394—806X), Journal of Pediatric Hematology and Oncology (ISSN: 1536-3678), New England Journal of Medicine (Resident 360). \n●\tMember – Core committee: American Cancer Society (A.C.S.) and American Academy of Pediatrics (A.A.P.) - Joint global pediatric Oncology taskforce.\n●\tAdvisor -World Health Organization, South East Asia for maternal and child health initiatives.( 2013-Ongoing) , Ministry of Health and Family Welfare ,Government of India ( 2014- Ongoing ) , American Academy of Pediatrics &American Cancer Society Global Taskforce on Pediatric Cancers.( 2014-Ongoing )\n●\tEditor – AAPI journal (American Association of Physicians of Indian Origin. Circulation -40,000)\n●\tVisiting Professorship in Hematology Oncology and Stem Cell Transplantation, Rajasthan University of Medical Sciences, India. ( 2009-Ongoing )\n●\tIndustry Advisor – Bayer, UniQure, Sanofi-Genzyme, Takeda, CSL Behring\n●\tDirector of International Bone Marrow Failure Consortium- India, part of the Global Hematology Initiative of Cohen Children’s Medical Center, New York, August 2015-2017. \n●\tCommittee member for the American Society of Pediatric Hematology Oncology Special Interest Group in Global Pediatric Hematology oncology. ( 2016- Ongoing)\n\n\n WORK EXPERIENCE \nNov 2017- Current Loma Linda University Children’s Hospital \n Director Division of Pediatric Hematology \n Director, Comprehensive Hemophilia Program\n Director, Comprehensive Sickle Cell Program \n Division of Pediatric Hematology Oncology and Stem Cell Transplantation\n Professor of Public Health, Loma Linda University School of Public Health \n\nMar 2017– Oct 2017 Pediatrics and Pediatric Hematology Oncology Practice \n Adventist Health Ukiah Valley, California \n\nSept 2015 –Aug 2016 Assistant Professor Pediatrics, Hofstra North Shore LIJ School of Medicine \n Section Head –Global Pediatric Hematology Oncology and Stem Cell Transplantation\n North Shore LIJ Health system.\n Associate Adjunct Faculty, Hofstra University School of Public Health.\n\nJuly 2012 – Sep 2015 The Steven and Alexandra Cohen’s Children's’ Hospital of New York at LIJ-North Shore \n Hofstra University - Pediatrics Hematology Oncology and Stem Cell Transplant Fellowship \n Chief - Jeffrey Lipton MD\n\nDec 2011- April 2012 Global Health : SMS Medical College and Group of Hospitals, Government of India \n Project Director for Project A.G.N.I. - Set up a regional Lead Poisoning prevention and \n anemia nodal center \n \n Course Director - Pediatric Subspecialty training module for Pediatricians at J.K. Lone \n Children’s Hospital for Government of India. \n\nDec 08- Dec 2011 The New York Medical College, Residency in Pediatrics \n Metropolitan Hospital, NY\n Maria Fareri Children's Hospital at Westchester.\n The Memorial Sloan Kettering Hospital. NY\n House staff on Stem Cell Transplantation service.\n \nApril – August 2008 Oklahoma State Medical Association (O.S.M.A.) Externship Program\n The Integris Baptist Teaching Hospital and Nazih Zuhdi Transplant Center\n\nRESEARCH EXPERIENCE \nNov 2017 – Ongoing: Current and ongoing – Director, Inherited Bleeding Disorder Experimental Therapeutics Program, Loma Linda University School of Medicine\nJan 2014 –July 2015 - Hofstra University School of Public Health \n Needs Assessment to barriers in cancer care for newly diagnosed patients in a resource \n Limited setting. \n Principal Investigator - Akshat Jain, Co-PI -Corrine Kyriacou \n\nJune 2012- July 2015 - Steven and Alexandra Cohen Children’s Medical Center \n Study – Non Invasive assessment of endothelial dysfunction in children with Sickle cell \n Disease. \n Co-Principal Investigator – Banu Aygun MD\n Study – Multicenter study assessing outcome of Reduced Intensity Conditioning for \n patients undergoing hematopoetic stem cell transplantation for Sickle cell disease . \n Co-Principal Investigator – Indira Sahdev MD\n \nJan 2012- Mar12 A.G.N.I. (Anterograde Growth Normalization Initiative) \n Project Director, Project of Government of India for establishment of Universal Lead \n Independent Pilot project to study effects of Elevated Blood Lead levels in children \n suffering from Developmental disorders- Adapted by W.H.O. 2014 for a National Level \n Lead Screening program, India \n \nJan 2009- Dec11 The New York Medical College, Metropolitan Hospital Center. NY\n Resident Physician – Hypothalamic volumes in patients with Growth Hormone deficiency.\n Maria Fareri Children's hospital / Dr.Richard Noto - Pediatric Endocrinology\n \nApril 2008-Dec 08 Nazih Zuhdi Transplant Institute, Integris Baptist Hospital, Oklahoma City\n Project – Single institution outcome study for Solid organ transplants\n Research Assistant Department of Hepatology\n \nOct 2007 – Dec07 Mount Sinai School of Medicine, New York, NY\n Project- Arterio-venous fistula post liver transplantation.\n Research mentor-Dr. Charissa Chang, Assistant Professor in Department of Liver Diseases. \n\nCERTIFICATION\n\n1.\tCalifornia State Medical License 8/2016- Present , New York State Licensure 8/2013-12/16\n2.\tAmerican Board of Pediatrics - Board certified, 11/14- Present\n3.\tAmerican Board of Pediatric Hematology Oncology – Board Certified , 06/2018- Present\n4.\tNeonatal Advanced Life Support 06/2009-Present \n5.\tPediatric Advanced Life Support 06/2009-Present \n6.\tECFMG Certification 12/2007-Present \n\nORAL PRESENTATIONS \n\n\n1.\tLeukemia and Lymphoma Society of America C.M.E. Symposium presentation – Leukemia and Beyond: Advances in Cancer Care and Blood Disorders in the 21st Century, October 2019\n2.\tLoma Linda University School of Medicine – Grand Rounds, Advances in the Management of Sickle Cell Disease, March 2019.\n3.\tLoma Linda University School of Medicine – Experimental Therapeutics in Sickle Cell Disease – New Horizons at Loma Linda , November 2018 .\n4.\tAdventist Health Ukiah , California - Neurological Defects of Iron Deficiency and Lead Poisoning in Humans , October 2017\n5.\tHofstra NorthWell School of Medicine - National Public Health Symposium on Global Public Health , Convener and Moderator ,April 2016 \n6.\tCleveland Clinic Children’s Medical Center, Ohio – Non BCR-ABL Myeloproliferative syndromes of childhood, January 19, 2016.\n7.\tChildren’s Hospital at SMS Medical College ,India – Pediatric Hematology Oncology Emergencies for the Tropics, November 13, 2015 \n8.\tHarvard Medical School, Boston Children’s Hospital Division of Pediatric Hematology – Advances in Global Hematology, Annual Hemophilia Twining symposium, August 2, 2015.\n9.\tNew York Medical College as Grand Rounds, Division of Pediatrics – Emergencies in Pediatric Hematology and Oncology, April 2015.\n10.\tMaurice A. Deane School of Law, Hofstra University, New York - Healthcare Access to Undocumented immigrants: Immigration reform and its impact, March 2015.\n11.\tPediatric Academic Society/Society of Pediatric Research (PAS/SPR) as platform presentation, Vancouver, BC - Global Child Health in Rich & Poor Countries Lessons Learned from Indigenous Health, May 3 2014.\n12.\tDepartment of Medicine and Medical Oncology, as Guest International faculty , SMS Medical College, India - Advances in Stem Cell Transplantation – January 2014.\n13.\tInternational health conference, Global Association of physicians of Indian Origin , New Jersey – Impact of Lead Intoxication in Low to middle income countries , August 2012.\n14.\t139st APHA Annual Meeting and Exposition 2011, Boston - Use of decision support in a Harlem pediatric emergency department to increase prescription of controller medicines to patients with poorly controlled asthma - Wilson Wang, Carolina Valez, Nicole Falanga, Vikas Bhambhani , Akshat Jain , Farhad Gazi, David Spiller, Paper no-227188 , November 2011 \n15.\tThe New York Academy of Medicine, Resident award night - False negative result in newborn screening for Congenital Adrenal hyperplasia - July 2009.",institutionString:"Loma Linda University Children's Hospital",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Loma Linda University Children's Hospital",institutionURL:null,country:{name:"United States of America"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"16",title:"Medicine",slug:"medicine"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"280415",firstName:"Josip",lastName:"Knapic",middleName:null,title:"Mr.",imageUrl:"https://mts.intechopen.com/storage/users/280415/images/8050_n.jpg",email:"josip@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review, to approval and revision, copy-editing and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. 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Research work continues to a better understanding of the processes involved and tailoring the desired properties of the final product. The most of ceramists has just worried up with the morphological, physical and structural quality of their products (Okada et al., 1986; Dubois et al., 1995; Nastro et al., 2006). However, one of the main ceramics features was not yet well concerned by the community, that is, its thermal behaviour. Urban buildings of equatorial and tropical countries are often subjected to constant solar radiation. Thus, thermal properties play a significant role in the quality of end-products. A better indoor ambient of the houses should be ever pursued. While technological properties of those materials are frequently found in the literature, information about the thermophysical characteristics of red ceramics is very scarce (Alexandre et al., 1999).
In the early eighties, a new physical device to generate and detect thermal waves was proposed (Vargas and Miranda, 1988). It has been widely used in last few years as a tool to measure the thermal properties of a large range of materials (Marín et al., 2002; Faria et al., 2005). The photoacoustic (PA) technique via OPC (an open photoacoustic cell) is used to evaluate the thermal diffusivity, an important parameter that determines the light-to-heat conversion efficiency, and furthermore, it allows us to study how heat diffuses through the sample (Perondi and Miranda, 1987). The thermal diffusivity is an intrinsic property of matter. Moreover, it is dependent upon the effects of composition and microstructural variables, as well as processing conditions. Thermal properties are very sensitive to amorphous–crystalline phase transitions of clays heated above 900 °C, typical temperatures applied in the manufacturing process of ceramic materials.
Clay deposit areas have a high economic potential, and soil mineralogical composition, plasticity and porosity are fundamental properties for industrial applications. The resulting ceramic products present a network of capillary pores that vary according to the firing cycle. Important ceramic properties such as hardness, water absorption, gas permeability, shrinkage, density, thermal properties, gas emission as well as the vitrification temperature range are intrinsically correlated to the porous system (Rice and Dekker, 1998).
In addition, the whole world presently draws increasing attention to the environment, requiring the adjustment of industrial activities according to laws and norms that rule the sector. Thus, increasing environmental problems related to climate changes and pollution are going attention and raising special concern regarding to the dispersal of industrial wastes. As a consequence, the society is demanding not only actions towards waste reduction but also measures for redirecting or post-using wastes mainly those of industrial origin. Most of the residues generating in the production process is normally handled by land disposal in certain areas, thus recycling of these residues may produce the value-added products and prevent environmental deterioration. As solid wastes are becoming a matter of increase world concern due to their amount as well as difficulty and cost of final disposal, ceramic products can well supply as matrices for industrial residues incorporation such as giving an option for the solid waste disposal with a possible increase in the properties of the clay ceramic products. The incorporation of wastes from several industrial activities is a technological alternative to reduce the environmental impact due to their indiscriminate disposal. One such a measure is the waste incorporation into intensive-produced clay ceramics like bricks and tiles (Parsons et al., 1997). This incorporation is now a common practice and benefits both, the industry that generates the waste and the ceramic industry that saves on the clay, which is its basic raw material. In some cases the incorporation also improves the properties of the ceramic product (Oliveira and Holanda, 2004).
Research works on the structural and physical changes that wastes, mainly industrially produced, cause to the final ceramic product has been rapidly expanding in these last two decades. See, for instance references in (Vieira and Monteiro, 2009). In spite of these examples of a continuous effort to incorporate wastes into clay ceramic motivated by technical and economical advantages, environmental issues are still a matter of concern. The firing stage during the clay ceramic process can promote the elimination of potentially toxic constituents present in the solid residues through their volatilization. However, the gas emission due to the clay firing process and its related atmospheric pollution may be enhanced as a consequence of an incorporated waste (Souza et al., 2008). It is known that the firing of clay ceramics in conventional furnaces using fuels such as wood, charcoal, heavy oil and natural gas generates appreciable amounts of gaseous components, mainly carbon dioxide (CO2), carbon monoxide (CO) and methane (CH4). Additionally to the atmospheric pollution, these gas sets could be harmful to the human health and can corrode equipments (Morgan, 1993).
Works on the effect of gas emission caused by the firing of clay ceramics incorporated with industrial wastes are practically inexistent. Therefore one of the mean objectives of this chapter was to investigate the gas emission resulting from the firing of clay ceramics incorporated with different industrial residues. Here, slag type of waste from steel refining operation and sanitary ware mass wastes were the selected residues.
In order to show methodologies to characterize ceramics here depicted, the samples under study were clay from Rio de Janeiro state and from São Paulo state. Firstly, the raw materials without residues is presented and throughout characterized. In a second stage, the aggregation of the residues is pointed out. Characterizations are performed and compared with the clays without residues.
Clayey soils from two sites of the Southeast Brazilian region were studied for the production of red ceramics. The samples preparation was pointed out in the following.
The raw material was collected from a quaternary sedimentary basin situated in Campos dos Goytacazes, from a layer localized between 0.30 m and 1.80 m below the surface, where large clay deposits are quarried as raw material for red bricks and tiles. About 20 kg of material collected in situ were dried, grounded, and passed through a sequence of sieves yielding a homogeneous powder with particle size smaller than 75 m, corresponding to 95 % of the original mass.
For technological measurements, a quantity of the powder was mixed with water and then extruded at 36 MPa into a rectangular prismatic mould with a 20x10 mm cross-section, cut into bars 100 mm long which were left drying in air for two weeks at room temperature. Before the firing process, the samples were subjected to an additional drying cycle in an oven at (110 5 °C) for 24 hours. Then, the sample weight and dimensions were measured just before starting the firing process. X-ray diffraction measurements were done on the same samples used for technological measurements.
To simulate the continuous sintering process of the ceramic material up to 1200 °C, and to accompany the changes that occur, 13 thermal treatment steps were chosen, each step being denoted TF henceforth. For firing temperatures up to 600 °C the heating rate was set to 2 °C/min. Once the desired TF was reached, the sample was left at constant temperature for 3 hours, and then cooled down to room temperature at a rate of 1.5 °C/min. For TF above 600 °C, the heating cycle was such that the sample was heated at a rate of 2 °C/min up to 600 °C, left at this temperature for one hour, and then heated at a rate of 10 °C/min up to the selected firing temperature, where it was left for 3 hours before cooling down to room temperature at a rate of 1.5 °C/min.
To perform the thermal characterization the raw material was passed through a sieve with nominal aperture of 75 µm (mesh 200 ASTM). In order to prepare the samples for analysis, a press (SHIMADZU) was used. 90 mg of each sample was weighed and submitted to a 9 tonne pressure for 10 minutes, using disc samples with 10 mm diameter and a thickness between 200 µm and 500 µm. After that, the samples were fired in a furnace (MAITEC 12 kW/32 A) at six different temperature steps, ranging from 900 to 1100 °C.
Finally, to analyse the gas emissions from the CG clay and its residue, rectangular 114.5 x 25.4 x 10 mm samples with 8 % of humidity were 20 MPa moldpress by mixing the clay with different amounts of 5 and 10 wt% of steel slage. Samples of pure clay were also considered for comparison. All samples were initially dried at 110 ºC in a laboratory stove and then fired in a continuous way, from room temperature to a maximum of 1100 ºC, inside a tubular model FT-1200 BI, MAITEC electrical furnace. The firing was conducted at a heating rate of 2 °C/min from RT to 500 ºC and 4 °C/min between 500 and 1100 ºC.
The raw material was collected from a neocenozoic sedimentary soil placed in Jundiaí city, 60 km far from São Paulo city in São Paulo state. The preparation process was similar to the sample of Campos dos Goytacazes for both applications. However, the J clays do not have such plasticity as CG clays. According to their chemical properties (sub-section 3.1), they can be considered fluxes clays mainly by the alkaline elements (K2O, CaO and MgO), which are responsible for the ceramic sintering. The value of K2O comes from the mineral illite, while CaO + MgO are linked with calcite and dolomite minerals. Al2O3 is related mainly to the kaolinite mineral.
The chemical composition and crystalline phases of the raw material with and without residues and only of the residues were presented. The microstructure of the samples as in function of the firing temperature was represented by X-ray diffractions.
Using X-ray fluorescence spectrometry methods described in previous work Mota et al., 2008), the percentual contribution of the main oxides present in our material was determined.
The chemical characterizations were obtained by energy dispersive X-ray spectroscopy (EDS), using a SHIMADZU equipment. The resulting values of this quantitative analysis from CG clay and its steel slag residue and from J clay and its sanitary ware mass residue are shown in Table 1 and Table 2, respectively.
Observing Table 1 and Table 2 we can classify CG clay as kaolinite-based clay (higher Al2O3) and J clay as illitic-based clay (higher fluxes oxides), as explained in the previous section. In addition to SiO2 and Al2O3, there are considerable amounts of Fe2O3, K2O and TiO2,, which is favourable for red ceramics production. Iron oxide accounts for the bodies´ red pigmentation after firing.
Oxides in wt% | CG Clay | Steel slag residue |
SiO2 | 46.42 | 10.29 |
Al2O3 | 27.90 | 21.5 |
MnO | 0.11 | 5.40 |
MgO | 0.71 | 10.33 |
CaO | 0.22 | 45.10 |
Na2O | 0.36 | - |
K2O | 1.67 | - |
TiO2 | 1.32 | 0.34 |
Fe2O3 | 9.10 | * |
P2O5 | - | 1.85 |
SO3 | - | 0.54 |
SrO | 0.18 | |
LoI | 11.96 | 12.96 |
* Total Fe from the residue (%) - 23.62 |
Chemical composition of the CG clay and steel slag (% in weight). The slag predominantly is formed by composites of Ca, Al, Fe, Mg and Si
Oxides in wt% | J Clay | Sanitary ware mass residue |
SiO2 | 59.61 | 64.8 |
Al2O3 | 21.19 | 21.5 |
MnO | 0.05 | 0.06 |
MgO | 1.07 | 0.78 |
CaO | 0.33 | 0.32 |
Na2O | 0.12 | 0.51 |
K2O | 2.33 | 2.53 |
TiO2 | 0.94 | 0.89 |
Cr2O3 | - | 0.05 |
P2O5 | 0.13 | 0.13 |
SO3 | - | 0.06 |
Fe2O3 | 5.45 | 5.96 |
ZnO | - | 0.03 |
ZrO2 | - | 0.13 |
LoI | 9.28 | 2.25 |
Chemical composition of the J clay and the sanitary ware mass residue (wt.%). The residue is a silt-clay with very low plasticity which should enhance the structural quality of the ceramic
The X-ray diffraction experiments were performed at room temperature Using the Co-Kα or Cu-Kα radiation of a Seifert URD65 diffractometer, equipped with a diffracted beam graphite monochromator. The CG clay diffractograms were obtained from 3 to 50º using the Co-Kα, while the slag steel residue from 3 to 70º.The J clay diffractograms were obtained from 3 to 75° with step sizes of 0.03° and accumulation time of 3 s. From the diffractograms the sample crystallinities were determined as the ratio between the integrated intensity of the sharp diffraction peaks to the total area of the diffraction pattern, which includes the non-coherent intensity. The CG clay sample was thoroughly analysed as in function of the firing temperature, whereas the J clay was just analysed the 110 ºC sample.
Fig. 1 shows the XRD patterns as a function of the firing temperature TF. A quantitative phase analysis was performed for the natural powdered soils of Campos dos Goytacazes using the Rietveld refinement method (Manhães et al., 2002). The Rietveld analysis was performed considering the angular range 10° < 2θ < 70°, thus not taking into account the illite phase due to its peak shape. Kaolinite is the main crystalline phase with 86% mass fraction, followed by quartz (5%), anatase (5%) and gibbsite (4%).
The diffractograms of the samples treated up to 400 ºC show a similar mineral composition with kaolinite as the major phase. Between 400 and 500 ºC the kaolinite dehydroxylation occurs, with the transformation to a non-crystalline phase, metakaolin: Al2Si2O5(OH)4 → Al2Si2O7+2H2O↑. The other crystalline phases (illite and quartz) remain unchanged up to 900 ºC. For this temperature range no more organic material is present in the amorphous component.. The main crystalline phases present in our non-treated samples were kaolinite (Al2Si2O5(OH)4), quartz (SiO2), anatase (TiO2), gibbsite (Al(OH)3), goethite (FeO(OH)) and illite ((K,H3O)Al2Si3AlO10(OH2)), while the sinterized samples showed the presence of mullite (Al6Si2O13), cristobalite (SiO2) and hematite (Fe2O3). Quantitative phase analysis using the Rietveld refinement method showed that kaolinite is the main crystalline phase responding for approximately 86 wt. %.
X-Ray diffractograms of CG clay as in function of firing temperature
Steel slag residue as processed diffractogram
X-ray diffractogram of J clay at room temperature
X-ray diffractogram of the sanitary ware mass residue
Fig. 2 shows the X-rays diffraction pattern of the steel residues. In the respective figure the predominantly formed crystalline phases of Ca and Fe had been identified to associate diffraction peaks. The rich phases in calcium (Ca) are silicates and the calcite. On the other hand, iron (Fe) is present in the form of magnetite and iron phosphate. Diffraction peaks of the magnesium manganese oxide were identified. In accordance to Fig. 2, Ca is present in the wollastonite (CaSiO3) and larnite (Ca2SiO4) form and also as carbonate (calcite – CaCO3). Mg and Mn are presented as magnesium manganese oxide (Mg6MnO8), while Fe is given in form of magnetite (Fe3O4).
Fig. 3 shows the XRD patterns of the J clay raw material. This diffractogram indicates the presence of a micaceous mineral, quartz, microcline, gibbsite and kaolinite.
Fig. 4 points out the sanitary ware mass diffractogram, which shows the presence of micaceous material, albite, anorthite, k-feldspars, clay minerals, quartz, and calcite. We observed a variety of flux materials. Feldspars and microcline are sources of alkaline flux materials, such as K2O and Na2O, which make possible the formation of a liquid phase above 700 ºC (Reed, 1976). The fluxing capacity of this residue, which is associated with lower porosity after firing, is also confirm by the presence of K2O and Na2O containing minerals. Then, the sanitary ware mass is the source of K2O and Na2O, which act as fluxes to improve the sintering process.
The samples dimension and mass were measured before and after each firing cycle so that the volumetric shrinkage and bulk densities could be straightforwardly determined.
Between 500 and 1200 °C, the porosity measurement consisted in measuring first the mass of the dry sample after firing at temperature TF, denoted henceforth as mTF, then two water-saturated sample masses: one, denoted as mi, inside water after 2 h boiling, the other, denoted as mo, outside taking care to remove the excess water from the sample surfaces. The sample open porosity was obtained as the ratio
For samples that undergone heat treatments at 110, 300 and 400 °C, we have adopted the conventional pycnometer method, the reason for this being that these samples usually exhibit larger porosity and lower particle cohesion than those treated at higher temperatures. In this way, we have avoided eventual sample disintegration due to prolonged water immersion.
The flexural rupture tension of our samples was determined by a universal testing machine using the three-point loading test with a crosshead speed of 0.1 mm/min, designed following the ABNT standard procedure17, method equivalent to ASTM C67. The bending strength was calculated from the breaking load using the relation
Figure 5 indicates that after 1000 °C the open porosity decreases abruptly from 39.6 % to 5.6 %, while the volumetric shrinkage and the bending strength both exhibit a large increase from 16.8 % to 40.0 % and from 9.0 MPa to 25.2 MPa, respectively. These results together with the X-ray diffraction data indicate that these changes are associated with recrystallization and sintering processes setting in between 1000 and 1200°C with the formation of mullite, cristobalite, and hematite phases, with great improvement of the ceramic properties. To further strength this aspect we present in Fig. 6 the correlations of the sample density, bending strength and volumetric shrinkage with the sample crystallinity, in the temperature range above 1000 °C. The solid lines in this figure correspond to the data linear regression. These results indicate that, indeed, these physical properties are all well correlated with the crystallinity changes taking place in our sample in this temperature interval.
The dashed lines in the bending strength, volumetric shrinkage, density and porosity plots correspond to the data fitting using a logistic function (
In Fig. 5 we present the evolution of the technological properties (bending strength (BS), volumetric shrinkage (VS), bulk density () and open porosity ()) as a function of the firing temperature. In order to single out the temperature point at which the phase transitions taking place in our sample affect most the corresponding physical properties we have performed a fitting of our data to a logistic curve of the following form,
where A, B, T0 and T are all adjustable parameters. The dashed lines Fig. 5 correspond to this logistic data fitting. In Eq. 1, T0 indicates the point at which the transition occurs whereas T gives us an idea of how wide this transition is. The resulting values obtained from this data fitting procedure for the parameters T0 and T are summarized in Table 3.
Data | T0 (°C) | T (°C) |
Open Porosity () | 1057.03 | 35.62 |
Bulk Density () | 1042.57 | 28.00 |
Volumetric Shrinkage (VS) | 1021.61 | 52.68 |
Bending Strength (BS) | 1079.97 | 80.39 |
Values of the data fitting parameters characterizing the temperature and its excursion where the main changes of the physical properties of our samples occur
Correlations of the sample density, bending strength and volumetric shrinkage with the sample crystallinity, in the temperature range above 1000 °C. The solid lines correspond to the data linear regression
The data shown in Fig. 6 also suggest some other interesting correlations among the different measured physical properties. For instance, the changes in bending strength and the volumetric shrinkage, as well as those of the porosity and density, seem to be well correlated.
We present in Figs. 7 and 8 the correlations between these physical properties. The straight lines in these figures correspond to the data linear regression. It follows from Fig. 6 that the bending strength and the volumetric shrinkage are well correlated up to 1050 °C, at which point a sharp discontinuity in the correlation takes place.
As to the correlation between the sample porosity and density, shown in Fig. 5, the same behaviour is observed, that is, a good correlation among these properties up to 1050 °C followed by a sharp discontinuity at this temperature. These critical transitions taking place around 1050 °C, are in good agreement with the values found from the logistic data fitting for T0, as shown in Table 3, as well as with the argument presented above indicating that a sintering process is set in around this temperature.
Correlation between the bending strength and the volumetric shrinkage. The straight lines correspond to the data linear regression
The phase transformations from X-ray diffraction data are well known. Up to 400 oC the dominant phase transformations are due to intense dehydroxylation processes of components, such as gibbsite and goethite, with kaolinite remaining as the major mineral phase. Between 400 and 500 °C, we observed a reduction in crystaline fraction, due the transformation of kaolinite to a noncrystalline phase, metakaolinite (Al2Si2O5(OH)4 Al2Si2O7 + 2H2O) took place, while the other crystalline phases (quartz, anatase and illite) remained unchanged up to 900 °C. Heat treatments above 1000 °C cause new structural changes with the formation of mullite, cristobalite, and hematite phases, among others.
Considering the technological measurements of the J clay and the sanitary ware mass residue, Table 4 presents the technological properties of volumetric shrinkage, bending strength and water absorption for the product fired at 980 ºC, considered the best temperature for commercial purposes.
Correlation between the samples porosity and density. The straight lines correspond to the data linear regression
Sample | Volumetric Schrinkage (%) | Bending Strength (MPa) | Water Absorption (%) |
J Clay | 2.1 | 3.3 | 20.3 |
J Clay 30 | 1.5 | 2.6 | 20.9 |
Technological properties of end-product ceramic (~980 ºC) without residue (J clay) and with 30 wt.% of sanitary ware residue (J Clay 30)
Comparing the Kaolinitic CG clay and the illitic J clay, we noted that the volumetric shrinkage value of J clay is half of the value of CG clay. In this case, J clay has advantages for the ceramic serial production in relation to dimensions uniformity. On the other side, CG clay presents a double value of bending strength, in relation to the J clay, i. e., more resistant pieces are shaped.
By analysing the thermal properties, some information can be collected from the material. In the following, we define the thermal properties and point out the values and their correlations with the sample microstructure.
Thermal diffusivity, a particular property that evaluates the heat propagation behaviour within the sample, is quite sensitive to the material structure as well as preparation and sintering conditions.
When values of thermal diffusivity (α) are evaluated from the amplitude data of the photoacoustic signal, we should pay attention to the microphone non-linear frequency response in relation to acoustic vibrations. Practically, all microphones present this irregularity. In our case, our microphone had a good linear frequency response above 20 Hz. In order to certify our set-up, a calibration measurement was performed. Figure 9 shows the dependence of the photoacoustical (PA) signal on the modulation frequency for the aluminium (Al) sample.
For frequencies used in this work, the signal exhibited a frequency dependency close to
Microphone output voltage as a function of the chopping frequency for the 25 µm thick Al sample. The signal behaves roughly as
The thermal conductivity (κ) is associated with thermal conduction, which is the phenomenon where the heat is carried from regions of high temperature to regions of low temperature in a material.
The thermal effusivity (ε) denotes the material thermal impedance and is a measurement of the heat energy stored in a solid per degree of temperature rise from the start of a surface heating process (Marín et al., 2002).
Here, thermal conductivity and thermal effusivity are reached applying the following expressions:
Experiments concerning with thermal diffusivity, samples thickness and specific heat capacity measurements were performed five, ten and three times to produce the deviations, respectively.
The thermal diffusivity experimental set-up is shown in Fig. 10. The sample is mounted directly onto a commercial electret microphone (Omnidirectional back electret condenser microphone cartridge, model WM-61A - Panasonic), fixed with a silicone grease, illuminated by the light beam from a He-Ne laser (Unilaser mod. 025) and modulated with a mechanical chopper (EG&G Instruments mod. 651), before it reaches the sample’s surface. It consists of an OPC configuration in the sense that the sample is placed on top of the detection set-up itself (Vargas and Miranda, 1988). As a result of the periodic sample heating by modulated light absorption, the pressure inside the cell oscillates at the chopping frequency and can be detected by the microphone. The resulting PA signal is then subsequently fed into a field-effect-transistor (FET) pre-amplifier and leads directly to a “Lock-in” amplifier (Perkin Elmer Instruments mod. 5210), where it is possible to obtain the photoacoustic amplitude and the phase signal, which are recorded as a function of the modulation frequency in an appropriate software program.
According to the model proposed by (Rosencwaig and Gersho, 1976) for thermal diffusion, the equation that leads us to the pressure fluctuation (P) in the air chamber is
where
Here, the amplitude of the PA signal decreases as
Experimental arrangement for the thermal diffusivity measurements following (
The amplitude of the PA signal for a thermally thick sample decreases exponentially with the modulation frequency as
Photoacoustic signal amplitude measurements as a function of the frequency square root for the 900 °C sample, together with the theoretical line
Taking values of thermal diffusivity from the literature, the cut-off frequency
Specific heat capacity illustrates how a material can store large amount of heat, without suffering drastic temperature changes. The specific heat capacity
Experimental arrangement for the specific heat capacity measurements
The temperature evolution was monitored from the ambient temperature up to the sample temperature saturation, obeying Eq. 7 and then the light was turned off and the temperature variation recorded until it reached the ambient temperature again (Eq. 8).
Here,
Experimental data and theoretical lines of rising (square) and decreasing (circle) temperatures as a function of time for the 1060 °C sample
As an example, Fig. 13 shows the experimental data (open symbols) and theoretical lines for the 1060 °C sample (CG clay).
Results of measurements of the thermal properties from CG clay are shown in Table 5 as a function of firing temperature.
Temperature (°C) | Thickness (µm) | Thermal diffusivity (cm2/s) | Specific heat capacity (J/cm3 K) | Thermal conductivity (W/cmK) | Thermal effusivity (Ws1/2/cm2 K) |
900 | 275±1.56% | 0.012±2.58% | 1.367±4.13% | 0.016 | 0.148 |
950 | 273±3.58% | 0.025±4.96% | 1.064±3.08% | 0.027 | 0.168 |
980 | 419±0.61% | 0.012±2.99% | 1.178±3.64% | 0.014 | 0.129 |
1020 | 323±1.41% | 0.021±2.16% | 1.201±1.34% | 0.025 | 0.174 |
1060 | 330±0.63% | 0.031±0.22% | 1.141±2.14% | 0.035 | 0.200 |
1100 | 323±1.56% | 0.013±2.58% | 1.067±1.37% | 0.014 | 0.122 |
Thermal properties values and samples thickness as a function of firing temperature with its standard deviation
Thermal diffusivity values ranged from 0.0016 to 0.0063 cm2/s and are in close agreement with the literature (Alexandre et al., 1999; García et al., 2002). Table 5 presents values for specific heat capacity that were around 1.0 (J/cm3K). Thus, we can infer that thermal conductivity and effusivity tend to follow the thermal diffusivity profile in relation to the firing temperature. Moreover, for this kind of material, thermal properties are strongly dependent on the material microstructure.
In relation to the structure, Fig. 1 shows the evolution of the X-ray diffraction patterns as a function of firing temperature. For natural clay the diffractogram reveals predominant phases of kaolinite, quartz and small amounts of gibbsite, illite, orthoclase and anatase. Following the treatment at 900 °C, illite, quartz, anatase and orthoclase remain unchanged and a hematite phase is revealed. Treatments at 950 °C or higher cause sample recrystallization in the Al-Si spinel (Okada et al., 1986) and a liquid phase formation. Data clearly show the evolution of mullite and cristobalite in samples over the temperatures 1060 °C and 1100 °C.
Analysing the thermal diffusivity and the diffractograms, we can explain that the lower diffusivity value in 980 °C and 1020 °C is possibly due to the Al-Si rearrangements, owing to a crystallization process followed by a lattice formation (Okada et al., 1986), according to
Equation 9 shows kaolinite
At 1100 °C, the thermal diffusivity decreases as explained by the reaction.
Through sintering at this temperature, formation of mullite
Summarizing, the red clay from Campos dos Goytacazes-RJ region are used mainly for bricks and roofing tiles. In general, ceramic plants fire their products at temperatures below 900 °C. In the raw state the red clay, as shown in Fig. 1, is composed of a high proportion of kaolinite clay mineral besides accessory minerals including oxy-hydroxide, illite, quartz, and anatase. In this case sintering is dominated by particle-to-particle contact mainly of metakaolinite platelets, resulting in a more open structure and also ceramic products of low quality. High porosity results in a lower thermal diffusivity and thermal conductivity. On the other hand, the sintering accelerates above 950 °C with drastic microstructural changes due to the formation of a vitreous phase, resulting in better densification behaviour of the red clay. As a consequence, the thermal diffusivity increases abruptly. However, a decrease in the thermal diffusivity occurred between 1060 °C – 1100 °C. This is due mainly to formation of mullite, which is characterized by a high proportion of oxygen vacancies that lead to low thermal diffusivity. It will be reasonable then to consider that the optimum firing temperature range for the studied red clay is above 950 °C.
Temperature (°C) | Thermal diffusivity (cm2/s) | Specific heat capacity (J/cm3 K) | Thermal conductivity (W/cm K) | Thermal effusivity (Ws1/2/cm2 k) |
900 | 0.003 ± 0.0004 | 0.61 ± 0.11 | 0.034 0.0013 | |
950 | 0.005 ± 0.0000 | 0.83 ± 0.02 | 0.061 0.0005 | |
1000 | 0.007 ± 0.0000 | 0.82 ± 0.13 | 0.072 0.0008 | |
1050 | 0.004 ± 0.0000 | 0.92 ± 0.09 | 0.061 0.0001 | |
1100 | 0.004 ± 0.0002 | 0.67 ± 0.11 | 0.045 0.0010 |
Thermal properties of the J clay as in function of some possible sintering temperatures
Temperature (°C) | Thermal diffusivity (cm2/s) | Specific heat capacity (J/cm3 K) | Thermal conductivity (W/cm K) | Thermal effusivity (Ws1/2/cm2 k) |
900 | 0.008 ± 0.0001 | 0.98 ±0.00 | 0.088 ± 0.0011 | |
950 | 0.004 ± 0.0005 | 1.12 ± 0.15 | 0.072 ± 0.0008 | |
1000 | 0.009 ± 0.0008 | 1.57 ± 0.04 | 0.148 ± 0.0005 | |
1050 | 0.006 ± 0.0004 | 1.43 ± 0.17 | 0.111 ± 0.0010 | |
1100 | 0.004 ± 0.0009 | 1.25 ± 0.02 | 0.082 ± 0.0009 |
Thermal properties of the J clay with 30% sanitary ware mass residues as in function of some possible sintering temperatures
Tables 6 and 7 show the thermal properties of the J clay and J clay with 30% residue, respectively.
Regarding to the ceramic thermal properties, the CG clay ceramic sample presented much higher values than the J clay ceramic. Thus, depending on the application, considering thermal properties we can use a kaolinite raw material if we need ceramics with fast thermalization or illitic clays for a better thermal isolation. We noted that the aggregation of 30% of sanitary ware mass residue in the J clay matrix generates higher values of the ceramic thermal properties.
The gas emission concentrations during the CG and J clays firing process were measured. The figures were displayed in such way that it is possible to compare the whole samples for each gas, obeying the CG clay samples and the J clay samples.
The following materials were studied in this present research: a) the CG clay and steel slag considered as a waste by the National Steel Plant (CSN) located at the south of the state. This slag was generated during the conventional oxygen blowing, LD (Linz Donawitz) process, of steel refining; b) The J clay and the sanitary ware mass rejects from a ceramic industry of São Paulo state.
The emitted gases from the firing process were quantitatively measured by means of a photothermal technique.
The gas released from the furnace was directly connected to an infrared model URAS 14, ABB gas analyser under a suction flux of 0.3 L/min This gas analyser detected and quantified simultaneously CO, CO2, CH4, NO, N2O, NH3 e SO2. Gas samples were collected 20 min. after settled temperature stages of respectively, 150, 300, 450, 550, 650, 800, 950, 1050 and 1100 °C. The samples were brought to room temperature following the inertial cooling of the resistive furnace.
The gas analyser measurement process is based on resonance absorption at the characteristic vibrational rotation spectrum bands of non-elemental gases in the middle infrared range between 2 m and 12 m. Because of their bipolar moment, the gas molecules interact with infrared emissions. For selectivity, the receiver is filled with the applicable sample components to establish reference and sensitivity to these components (~1 ppm). It consists of the cell divided into two identical compartments: one in the measuring cell, through which the sampled gas is flowed, and the other acts as reference, filled with nitrogen. The light emitted from a hot filament is modulated by a mechanical chopper and divided by a beam splitter. Each beam goes simultaneously through the measuring cell and the reference cell. The detector consists of two sealed chambers separated by a diaphragm capacitor. Both chambers are filled with pure gas of the chemical species under study. The light beams emerged from the sample and reference cells reach independently the two detector chambers, causing a differential pressure that is proportional to the light absorption by the sample. The pressure difference is converted by the diaphragm capacitor into an electrical signal. A detailed description of the Uras performance can be found in the literature (11). Before each sample analyses the cells were calibrated using pure standard N2.
Figures 14 and 15 show the released CO2 and CO gases as in function of the temperature from the CG clay with (5%, 10%) and without (0%) steel slag residue in different concentrations in weight. The other gases had not presented significant values.
CO2 profiles as in function of the firing temperature for the samples with 0 %, 5 %, and 10 %
CO2 concentration values were emitted more significantly in the presence of the residue. Generally, carbon composites, as CO2, in the range of 300 °C to 500 °C are emitted due to the organic matter oxidation. Moreover, the reaction of the kaolinite and goethite dehydroxilation deals to a metakaolinite, that is, an amorphous phase.
CO profiles as in function of the firing temperature for the samples with 0 %, 5 %, and 10 %
The CO2 emission in temperatures higher than 850 °C, is possibly due to: the hydroxil (OH) release, proceeding from the gases that were locked up in the pores, which are set free later when the pores begin processes of volumetric reduction, due to the high temperature; the chemical dehydration of minerals that contains mica (muscovite); and the calcite decomposition (CaCO3 = CaO+CO2). Values reached in this section were just proportional to a laboratory furnace.
CO2 emmited during the ceramic firing process as in function of the firing temperature
Figures 16 and 17 show the CO2 and CO emissions as in function of firing temperature from the J clay without and with 30% in weight of sanitary ware mass residue. Firstly, we observed that the addition of the residue diminishes the amount of CO2 emission. The amount of CO2 emitted between 300 and 550 ºC has the same explanation previously cited, that is, due to organic matter oxidation and the dehydroxilation of clay minerals.
CO emmited during the ceramic firing process as in function of the firing temperature
Here, red ceramic samples from Rio de Janeiro state and from São Paulo state were analysed as in function of firing temperature. In order to study the ceramics quality, technological essays were prepared. Comparisons between the Kaolinite CG clay and the illitic J clay were made, indicating the advantages and disadvantages of each specimen.
The thermal property of red ceramic samples as well as their crystalline phases were analysed as a function of sintering temperature. Photothermal techniques were used to measure the thermal properties and the microstructures were identified by x-ray diffraction, in order to compare structural and thermal features of the samples. It was shown that there is an intrinsic relationship between the structure and the thermal diffusivity. When the crystalline structure undergoes strong perturbations the thermal diffusivity values decrease and vice-versa. When liquid phases achieve the highest concentration at around 1060 °C (CG clay) and 1000 ºC (J clay), the thermal diffusivity shows its maximum peak. Afterwards, there is a decrease, although the thermal diffusivity maintains high values, due to mullite enhancement and vitreous phase consolidation in the red ceramics. The J clay sintering temperature is lower than to the CG clay, due to a larger amount of flux material.
Thermal property values are consistent with the literature. As the specific heat capacity has values of approximately unity, thermal conductivity and effusivity follow that of thermal diffusivity. Considering thermal properties, it was shown that red ceramic sintering temperatures should be greater than 950 °C, but below 1060 °C from both clays.
The steel slag investigated, considered as a steelmaking waste, has an elevated amount of Ca, Fe, Mg and Si. The main crystalline phases identified were magnetite, Fe3O4, calcite, CaCO3, magnesium manganese oxide, Mg6MnO8 and calcium silicate, Ca2SiO4, CaSiO3. The incorporation of steel slag into clayey ceramics, must be done in amounts of up to 10 wt.%. In relation to the steel slag incorporation, it had been mainly detected CO and CO2. Comparing the diverse percentages of residues into the ceramic mass, it observed that the CO2 concentrations decrease in the range of 300 °C to 500 °C, when increased the percentage of residue to the mass. On the other side, between 500 °C and 950 °C, there was a reasonable increase of the concentration (in relation to the pure clay), when the residues percentage was enlarged. The calcite starts to decompose around 675 °C and its complete decomposition occurs up to 950 °C. When mixed to another minerals, the calcite presents lower temperature of decomposition (880 °C, approximately).
It is possible that sanitary ware residues can attenuate the pollutant gas release from the ceramic firing. We concentrate in this chapter the CO and CO2 gases, in order to facilitate the point of view of our study. It will appear elsewhere the complete set of measured gases from this research.
The authors thank the Brazilian agencies FAPERJ, CNPq and CAPES for the financial support.
Two specific trends can be noticed in modern chemical analysis. One is the continuous demand for more sensitive and accurate analytical methods. The other is the desire for simpler methods that require as little as possible human intervention. One of the various procedures to make the analytical methods more sensitive and accurate is the use of specific chemical changes (e.g., derivatization) applied on the analytes or even on the whole sample. However, these changes frequently involve more human intervention than the direct use of advanced instrumentation. For this reason, the methods involving chemical changes such as derivatizations are not necessarily the first choice when selecting an analytical method. Nevertheless, in many cases, the benefits of derivatization are more important than the disadvantage of requiring human intervention, and for this reason, derivatization is still frequently used in the analytical practice. Also, modern GC, GC/MS (or GC/MS/MS) instrumentation may offer autosampling with the capability of adding reagents to the sample, as well as stirring, heating, and injecting the sample at specific time intervals in the GC system. This type of instrumentation may reduce significantly the human handling involved in derivatization.
\nVarious chemical changes can be performed on an analyte in order to make it suitable for a specific method of analysis. The most common is derivatization, but other chemical changes can be utilized, for example, pyrolytic decomposition and, in the case of polymers, polymer fragmentation using reagents. The choice depends on the nature of the analyte, the sample matrix, the intended changes in the analyte properties, and the analytical method to be used.
\nThe addition of a reagent on a sample may produce a chemical reaction only with the analytes without affecting the matrix. However, it is also possible that some matrix components are derivatized unintentionally. Usually, it is preferable to have only the analytes derivatized since in this way a better separation from the matrix is expected. Some derivatizations are used in the sample cleanup or concentration process. Also, the derivatization process may be combined with simultaneous extraction and concentration of the sample or may be followed by a second preparation step before the chromatographic analysis. More frequently, the derivatization is done to change the analyte properties for the core analytical procedure (GC, GC/MS, etc.).
\nDerivatization can be applied before the core chromatographic process or after it. Precolumn derivatization takes place before the separation and postcolumn derivatization after it. In GC precolumn derivatization is much more common and most derivatizations are performed “offline.” There are however derivatizations that can be done “online,” for example, in the injection port of the GC such as some methylations using tetramethyl ammonium hydroxide (TMAH). Postcolumn derivatizations are performed only for enhancing the detectability of the analytes. Typically, they must be done “online” and should be completed in the specific time frame needed by the analyte to reach the detector.
\nA wide variety of derivatization reagents and procedures are described in the literature, with the reagents carrying specific moieties that provide a desired property to the analytes, as well as with specific reactive groups that permit the reaction with the analyte. Multiple step derivatizations as well as derivatizations followed by a second one are known.
\nDerivatization is not always the first step in sample preparation. Sample preparation typically includes other operations, besides derivatization. Some of these steps are more complex such as sample cleanup or concentration and others more simple such as pH adjustments, addition of proton acceptors or donors, change of the medium (from one solvent to another), and addition of catalysts to enhance the derivatization, and these may be necessary for a successful derivatization.
\nAlthough derivatization is performed in order to make possible or to improve the results of a chemical analysis, there are also some disadvantages of using derivatization. Besides the potential need of more manpower for the analysis, the addition of more operations applied on the sample (including the analytes) can be a source of additional errors. In particular the involvement of a chemical reaction that may not be perfectly controlled can bring significant errors in the analytical results. To minimize the potential errors when using derivatization, specific aspects of the derivatization must be considered in its choice, such as the efficiency of the chemical reaction used in the derivatization, the stability of the derivatized analytes, the availability of reagents and necessary equipment, and the time necessary for performing the analysis. For a given analyte or group of analytes, the reaction with the derivatization reagent must be complete or at least close to complete, must take place in a length of time that is not prohibitive, and must have very little loss of the analyte with formation of artifacts or decomposition products. Only when such criteria are satisfied can a specific chosen derivatization be applied successfully.
\nThe application of derivatization in chromatography is the subject of many studies. Numerous derivatizations have been reported in journals (e.g.,
For GC analysis, the effect of derivatization can be beneficial in a variety of circumstances. Some of the most common uses of derivatization for improving the GC separation are the following:
(a) Derivatization that replaces active (polar) hydrogen atoms in the analyte to decrease its boiling point. The active hydrogens in a chemical compound typically enhance the capability to form hydrogen bonds and increase the compound polarity. For this reason, many compounds containing active (polar) hydrogens are not volatile, the volatility being necessary for using GC or GC/MS as a core analytical method. Derivatization can be used to replace active hydrogens from an analyte Y-H (or Y
In reaction (1), the reagent R-X contains an “active” group X and a group R that carries a desired property (e.g., lack of polarity for GC). Group R in the reagent can be a low molecular mass fragment such as CH3 or C2H5, a short-chain fluorinated alkyl in alkylation reactions, Si(CH3)3 or other silyl groups in silylations, COCH3 or short-chain fluorinated acyl groups in acylations, etc. An example of a chromatogram resulting from the GC/MS analysis of a silylated tobacco sample is given in Figure 1. Tobacco contains many hydroxy acids such as malic, trihydroxybutanoic, citric, quinic, glucuronic, and chlorogenic. Also, it contains monosaccharides (e.g., glucose, fructose), disaccharides (e.g., sucrose), and even trisaccharides. None of these compounds are volatile, having numerous active hydrogens. The replacement of these hydrogens with Si(CH3)3 by silylation renders these compounds volatile, and they can be analyzed by GC/MS as seen in Figure 1.
(b) Derivatization for enhancing the separation. Specific moieties added to an analyte may be necessary for enhancing the separation. This is frequently practiced for general GC separations and is also very useful for the separation of chiral molecules (see Section 4). The derivatized analytes may have significantly different properties from each other, for example, regarding polarity and implicitly in their boiling point, allowing separations that are difficult to achieve otherwise. Also, derivatization may generate more significant differences between the analytes and the matrix components.
(c) Derivatization that replaces active hydrogens in the analyte to improve the behavior of the analyte in the chromatographic separation. The chromatographic column (e.g., a capillary column coated with a bonded stationary phase) may display additional capability to interact with polar molecules, besides the intended interactions due to its bonded phase. This may come, for example, from the silica wall of the column. Secondary interactions taking place with only a portion of the molecules of the analyte generate peak tailing. This is exemplified in Figure 2 which shows a hypothetical case of two different types of interaction between the column and a specific molecular species.
(d) Derivatization for the improvement of stability of a compound. This stability may refer to thermal stability, a property which overlaps to a certain extent to what was described at point (a). However, even some volatile compounds may be further thermally stabilized by derivatization. Also, chemical stability can be enhanced by protecting specific groups in the analyte using derivatization. For example, thiols can be protected using derivatization against oxidation by the traces of oxygen in the heated injection port of the GC.
GC/MS chromatogram of a silylated tobacco sample, with separation on a DB-5 MS column from Agilent (Agilent Technologies Inc., Wilmington, DE, USA) (Note: an internal standard I.S. was added to the sample).
Peak tailing due to multiple retention mechanisms.
The choice of the appropriate derivatization is not always a simple task. The replacement of a hydrogen atom with a group of atoms may increase the molecular weight of the derivatized analyte. In such cases, it must be verified that the increase in the molecular weight by derivatization brings no or only a small increase in the boiling point of the analyte. Most of the time, low molecular weight substituents such as CH3 or Si(CH3)3 are preferable for GC analysis to the active hydrogens for achieving the previously described goals. Large substituents may increase the boiling point too much and make the compound not acceptable for GC analysis.
\nBesides replacement of active hydrogens, other derivatization reactions can be utilized. For example, condensation reactions may decrease the boiling point and improve the thermal stability of an analyte. However, the generation of new active hydrogens must be avoided in condensation reactions or must be followed by a second derivatization.
\nThe compounds with structures that are mirror images to each other are indicated as enantiomers, and their molecules are not superimposable, having the property called chirality. Chirality is commonly caused by the existence in the molecule of at least one tetrahedral carbon atom substituted with groups that are different. However, chiral molecules may be generated with a phosphorus or a sulfur chiral atom. Not only chiral centers (such as an asymmetric carbon) generate enantiomers, but a chiral axis or a chiral plane can lead to enantiomers. The chirality in an enantiomer is specified using the symbols R and S based on specific rules. For the assignment of a symbol R or S to a chiral carbon, the substituents are arranged in a sequence a > b > c > d. For the four atoms directly attached to the asymmetric carbon, a higher atomic number outranks the lower, and a higher atomic mass outranks the lower mass. For the same atoms directly attached to the asymmetric carbon, the priorities are assigned at the first point of difference. After the sequence is established, the molecule is oriented in space with the group “d” of the lowest priority behind the asymmetric carbon. When viewed along the C─d bond (from C) and the three substituents a, b, and c are oriented clockwise, the compound contains an R asymmetric carbon, and it contains an S asymmetric carbon for counterclockwise arrangement.
\nMore than one asymmetric carbon can be present in a molecule, as in the case of carbohydrates. The stereoisomers generated by more than one asymmetric carbon can be mirror image one to the other (enantiomers) or may have different steric arrangements being diastereoisomers. These types of molecules are schematically shown in Figure 3.
\nCompounds with two chiral centers.
The (S,S)- and the (R,R)-compounds from Figure 3 are enantiomers, while the (S,R)-compound is a diastereoisomer to both (S,S)- and to (R,R)-compounds (it is an enantiomer to the (R,S)-compound). The gas chromatographic separation of enantiomers can be done only using chromatographic columns having chiral stationary phases. The derivatization of enantiomers with non-chiral reagents generates molecules that remain enantiomers. This type of derivatization may improve the chromatographic separation from other molecules, but the derivatized compounds of remaining enantiomers cannot be separated except on chiral stationary phases. Sometimes, better separation can be obtained even between the enantiomers (on chiral chromatographic columns) after derivatization. One such example is the separation of (R)- and (S)-nornicotine derivatized with isobutyl chloroformate on a chiral Rt-BDEXsm column with separation improved compared to that of underivatized enantiomers [6]. The derivatization reaction is indicated below:
\nDiastereoisomers can be separated on chromatographic columns with non-chiral stationary phases which offer a much wider possibility to select the column. For this reason, an alternative procedure toward the separation of enantiomers is using derivatization with chiral reagents. This type of derivatization generates diastereoisomers which can be separated on non-chiral stationary phases.
\nA discussion on the separation of enantiomers on chiral phases without derivatization is beyond the purpose of this chapter. Numerous publications are dedicated to this subject, including papers published in general chromatography journals or in dedicated journals (e.g.,
The separation after derivatization with a pure enantiomer reagent is based on formation of diastereoisomers that can be separated on regular stationary phases. Depending on the nature of the analyte and of the derivatization, different separation techniques can be applied. A variety of common columns are used for such GC separations. The choice of the column is again dependent on the analyte and the derivatization procedure. For example, α-substituted organic acids such as α-chloropropionic, α-bromocaproic, etc. can be derivatized with a specific enantiomer of an amino acid ester (e.g., ethyl 2-aminopropanoate) in the presence of a peptide coupling reagent (benzotriazol-1-yl-oxy-tris(dimethylamino)-phosphonium hexafluorophosphate or BOP) in a reaction of the type:
The derivatized acids that are now diastereoisomers (R,S) and (S,S) can be separated on a common capillary column (e.g., a DB-1701 column from Agilent). Another example of derivatization with a chiral reagent is that of methamphetamines with (R)-menthyl chloroformate. This derivatization allows the separation of over-the-counter (R)-methamphetamine from the illicit (S)-methamphetamine. The reaction of the (R)-enantiomer is indicated below [8]:
The separation of the (R,R) and (S,R) derivatives was possible on a non-chiral column for a GC/MS analysis.
\nGas chromatography (not coupled with mass spectrometry, GC/MS being separately presented) used as an analytical technique can involve various detectors. The variety of such detectors is rather large, and several types include the following: thermal conductivity detector (TCD), flame ionization detector (FID), nitrogen-phosphorus detector (NPD), electron capture detector (ECD), flame photometric detector (FPD), photoionization detector (PID), electrolytic conductivity (Hall), sulfur chemiluminescence, nitrogen chemiluminescence, aroyl luminescence detector (ALD), atomic emission detector (AED), helium ionization detector (HID), vacuum ultraviolet (VUV) absorbance, infrared Doppler (IRD) absorption, FID with catalytic conversion of all analytes in CH4 (e.g., Polyarc system [9]), etc. The derivatization with the purpose of improving detectability in GC is determined by the type of detector utilized. Most derivatizations are performed precolumn, even if they are applied only with the purpose of improving detection. However, it is important that the derivatization for improving detection does not deteriorate the separation. Preferably, both the detection and the chromatographic separation are improved by the same derivatization. Some specific postcolumn reactions applied to the analytes are part of certain types of detectors such as chemiluminescence detectors, atomic emission detectors (AED), and FID with catalytic conversion into CH4. Some of these chemical changes in the analytes are not necessarily classified as derivatization reactions.
\nNo specific derivatization is usually recommended to improve sensitivity when using nonselective detectors such as TCD and FID. However, in some cases when the detector is not sensitive to a specific analyte, such as formaldehyde or heavily halogenated compounds, derivatization can be used to enhance detection.
\nIn case of NPD detector, derivatization with nitrogenous compounds can be done, which should give a higher sensitivity. However, this type of derivatization is not very common. An adverse result occurs for the NPD detectors when silylation is performed on the sample. Besides a possible reduction in the NPD response on silylated compounds containing nitrogen, a drastic decrease in the lifetime of the detector may occur, probably due to the excess of silylating reagent that commonly is injected with a derivatized sample and affects the alkali active element of the NPD.
\nThe response of the photoionization detector (PID) depends on the ionization potential of the analyte, and compounds with higher ionization potential are not sensitive in PID, while those with lower ionization potential may have excellent sensitivity, as low as 10−12 mg of sample. A derivatization resulting in lowering the ionization potential of the analyte may be beneficial for PID detection. However, derivatization for enhancing PID response is not frequently used.
\nSome detectors such as electron capture detectors (ECD) may benefit very much from certain derivatization types. ECD (as well as negative chemical ionization mass spectrometry or NCI-MS) can be extremely sensitive, but they are selective to compounds that are able to form more stable negative ions. ECD, for example, can have sensitivity as low as 10−13 mg of analyte in the detector compared to the best sensitivity of FID that can be 10−8 to 10−11 mg of analyte. The efficiency of the process seems to be related to the ease of attaching an electron on the molecule. In ECD this process can be written as follows:
With some exceptions, ECD response can be correlated with the electron affinity of the analyte [4]. In general, the halogen substituents increase the sensitivity in ECD in the order I > Br > Cl > F. Multiple substitutions seem to have a cumulative effect. Besides halogens, nitro groups seem to have an effect similar to chlorine groups. For aromatic compounds, the substituents affect the sensitivity of the ECD according to their electron withdrawing capability. Strong electron withdrawing groups such as NO2 increase the sensitivity of the detection, while electron donating groups reduce it.
\nA variety of substitution groups containing electronegative elements (halogens) or nitro groups can be attached to an analyte. The procedure to attach these groups is in most cases the typical substitution of an active hydrogen in the analyte Y-H with a group R from a reagent R-X that has the appropriate active X group. Some groups used for enhancing ECD (as well as NCI-MS) sensitivity following an alkylation or aryl derivatization reaction are shown in Figure 4, and several substitution groups introduced by acylation, chloroformylation, or sulfonation used for the same purpose are shown in Figure 5. Besides alkylation or aryl derivatization, other derivatization techniques used to replace an active hydrogen are applied to introduce into a molecule as a substituent containing halogens or nitro groups enhancing significantly the detectability of the derivatized analytes by ECD (as well as NCI-MS). Silylation, for example, can be used for this purpose when silyl groups used for derivatization contain halogens. Several silyl groups containing halogens that can be attached to an analyte by silylation with special reagents are given in Figure 6 [4].
\nSubstitution groups used in alkylation and aryl derivatization for enhancing ECD (and NCI-MS) detectability (the masses are considered only for the most abundant isotope.).
Substitution groups used in acylation chloroformation and sulfonation for enhancing ECD (and NCI-MS) detectability.
Substitution groups used in silylation for enhancing ECD (and NCI-MS) detectability.
The most powerful tool used for compound identification purposes is very likely mass spectrometry (spectroscopy). This technique is capable to provide information from very low amounts of material such as that eluting from a chromatographic column and can be easily coupled with a gas chromatograph. Most analyses performed with MS detection (GC/MS or GC/MS/MS) are using EI+ ionization mode with electron impact at 70 eV. The electrons interact with the molecule A to eject an additional electron leaving a positively charged species (with an odd number of electrons) of the type A▪+. The ions also receive energy during electron impact and the excess of energy induces fragmentation. For most molecules, this process can be written as follows:
The fragments Bi+ are commonly but not always with an even number of electrons. The formation of molecular ions takes place with a range of internal energies, and more than one fragmentation path is possible for a given molecule. Also, the fragments can suffer further fragmentations. In general, the most abundant fragment ion results from the fragmentations that form the most stable products (ion and neutral radical). The abundance of a fragment ion is affected by its stability. For this reason, the intensity of the response of a mass spectrometric detector can be very different for different molecular species, and the prediction of this intensity is difficult. As a result, the improvements in the sensitivity in EI + −type mass spectrometry (in GC/MS using EI+ ionization) are not usually sought (but not impossible) through derivatization.
\nDerivatization for enhancing sensitivity is, however, frequently applied in NCI-MS. In this technique, the electrons interact with the molecules of the CI gas which is lowering their energy but without forming ions. The ionization of analyte molecules takes place by interaction with the low-energy electrons or with already formed negative ions by electron capture, dissociative electron capture, ion pair formation, or ion molecule reaction. The ionization process with the formation of negative ions is efficient only for molecules with positive electron affinities. For this reason, the sensitivity in NCI-MS is highly dependent on the electron affinity of the analyte, similarly to the sensitivity in ECD. For enhancing the electron affinity, the derivatization with reagents containing, for example, fluorinated moieties (indicated in Figures 4, 5, 6) is practiced. The sensitivity of the analytical methods where such derivatization is applicable can have very good sensitivity. For example, derivatization with heptafluorobutyric anhydride of aromatic amines that are present at low trace level in cigarette smoke leads to limit of detection (LOD) values as low as 0.05 ng/cig. for compounds such as 4-aminobiphenyl [10, 11].
\nThe fragmentation pattern generated by EI+ ionization mode that generates a specific mass spectrum of a molecule is very likely the most utilized technique for the identification of the molecular species. For this identification, large libraries of mass spectra are available, and computer algorithms are used for automatic searches. The identification of compounds using mass spectroscopy is not a simple process even with the capabilities offered by the electronic searches in the mass spectral libraries. This is particularly true for analysis of complex mixtures or when the analyzed compound is present in traces. Some compounds do not have a very characteristic mass spectrum, or during the chromatographic process, the separation is not achieved, and it is difficult to make an identification due to the spectra overlapping. Also, numerous compounds may have a mass spectrum that matches more than one compound (with a good quality fit). In such cases, a derivatization with the purpose of obtaining a compound that forms more informative fragments in the mass spectrum can be very useful.
\nThe fragments from derivatized compounds can be used for the identification of unknown compounds using library searches and even when the mass spectrum is not available in the libraries. As an example, the derivatization by silylation allowed the identification of a new pentacyclic triterpenoid present in several bioactive botanicals [12]. An unidentified compound with MW = 456.7 was detected by LC/MS/MS in a rosemary extract. The structure of the compound was elucidated after silylation of the plant material based on the comparison of mass spectrum of the unidentified compound with that of silylated betulinic acid. The new compound was identified as (3β)-3-hydroxy-lupa-18,20(29)-dien-28-oic acid (or betul-18-en-oic acid). The mass spectra of the two acids are shown in Figure 7.
\nMass spectrum of silylated betulinic acid and that of silylated betul-18-en-oic acid.
The two mass units difference between different fragments from the mass spectra of the two compounds allowed the identification of the new compound structure. Neither free betulinic acid nor betul-18-en-oic acid are volatile, such that the use of GC/MS for identification was possible only after derivatization.
\nAnother special procedure that may be utilized for compound identification based on mass spectra is the use of two parallel derivatizations, one of them being done with an isotope-labeled reagent. Common labeling isotopes are 2H (deuterium, d), 13C, 15N, etc. One such isotopic labeling can be done, for example, using silylation with d18-N,O-bis(trimethylsilyl)-trifluoroacetamide (d18-BSTFA). Derivatization of an aliquot of sample with regular BSTFA and another with d18-BSTFA provides a pairing chromatogram with peaks at retention times that have only small differences from the first but with spectra differing by a number of units. The comparison of the spectra for corresponding peaks (based on retention time) of a given compound allows the calculation of the number of silyl groups attached to that compound. In addition, the fragmentation in the spectra can be better interpreted allowing easier compound identification.
\nDerivatization in GC/MS analysis may have multiple other utilizations and benefits. For example, quantitative analysis frequently utilizes isotopically labeled internal standards. In an analysis with multiple analytes, addition of an isotopically labeled internal standard for each analyte may become a complex process. When a derivatization is involved in the analysis, this can be done with a non-labeled reagent for the analytes in the sample, while the internal standards are obtained by derivatization of standards with the same reagent but isotopically labeled. Such technique has been proven to be very successful, for example, in the analysis of multiple amino acids (but using an LC/MS/MS procedure [13]).
\nDerivatizations as chemical reactions can be classified as follows: (1) reactions with formation of alkyl or aryl derivatives, (2) silylation reactions, (3) reactions with formation of acyl derivatives, (4) reactions of addition to carbon-hetero multiple bonds, (5) reactions with formation of cyclic compounds, and (6) other reactions specific to a certain analysis. The selection of the derivatization reaction is typically done based on the desired property to be brought to the analyte and its possible reactivity. For this reason, the reagent is selected to have moieties that add the desired property to the analyte and also to have the capability to react with the specific functional group of the analyte. The matrix of the sample also has a role in the choice of a specific derivatization procedure. Initial matrix of the sample is not always suitable for derivatization, and in some cases preliminary sample preparation is necessary to change this matrix. The change can be as simple as drying the initial sample but can also be rather complex [14]. Table 1 gives a simplified view of preferences for the choice of a derivatization reagent for compounds containing active hydrogens [14].
\nDerivatization preferences for compounds containing active hydrogens.
Besides functionalities with active hydrogens, other functionalities can also be derivatized. Compounds containing carbonyls can be derivatized, for example, using condensation reactions. Some analytes may contain multiple functional groups such as the amino acids. Specific derivatization reactions can be selected for such cases.
\nThe formation of alkyl or aryl derivatives is applied to replace the active hydrogens from an analyte with an alkyl (R) or aryl (Ar) group. The replacement can be done in functionalities such as OH, COOH, SH, NH, or CONH. For example, the derivatization with short-chain alkyl bromides or iodides has numerous analytical applications for compounds such as steroids, amino acids, catecholamines, sulfonamides, phenols, barbiturates, organic acids, and mono- and oligosaccharides. A large number of reagents R-X are known, and in a simplified approach, it can be considered that R is carrying a specific property and X a specific reactivity, although the reactivity of a reagent is influenced by both R and X components of the molecule. The type of moiety R and that of reactive group X are guiding the selection process of selecting a reagent for a specific derivatization.
\nIn most alkylation reactions, the analyte acts as a nucleophile (Y
Various reagents and conditions were utilized in the derivatizations for analytical purposes. As reagents R-X for alkylations, one of the most commonly used are the alkyl halides, especially alkyl iodides and alkyl bromides. Because some of the derivatizations can be slow and inefficient depending on the analyte and on the reagent, the reaction rate becomes an important parameter for the analytical applicability. The reaction with an alkyl halide for the preparation of methyl or ethyl substituents, for example, is frequently performed either with a specific methylation reagent, in the presence of a catalyst, or in some instances using a particular solvent. The enhancement of the alkylation efficiency can be achieved using several other procedures. For example, for the analytical alkylation of carboxylic acids, specific cryptands such as crown ethers can be used to solvate the alkali metal portion of an organic acid salts, allowing the anion to be freer and increasing the rate of nucleophilic substitution. One other approach for enhancing the alkylation efficiency is the use of phase transfer alkylation. This approach is based on the formation of a compound easily extractable in an organic phase and on the displacement of the equilibrium in the direction of the formation of the desired product.
\nOne different way of enhancing the alkylation efficiency is the use of different alkylating reagents besides short-chain alkyl bromides or iodides. One example of a halide that is particularly reactive is pentafluorobenzyl bromide. This reagent can be used for the derivatization of a variety of compounds containing active hydrogens. Another reactive halide is 2-bromoacetophenone (phenacyl bromide). This reagent is used mainly for the alkylation of compounds containing more acidic hydrogens such as carboxylic acids. Another example of methylation using a special reagent R-X is applied on carbohydrates [15]. This methylation uses methylsulfinylmethanide anion. The reagent is prepared from dry DMSO and NaH or KH in a reaction as follows:
A polyol or a monosaccharide dissolved in DMSO is easily methylated with methylsulfinyl-methanide anion.
\nOther alkylating reagents are known (different X in R-X), also reacting in a nucleophilic substitution. For example, dimethyl sulfate can be used for alkylations. Alkylfluoromethyl-sulfonates are even more reactive than sulfates, and the reaction may take place with the active hydrogen even from alcohols or amines as follows:
Even tertiary amines, such as pyridine, also react with this type of reagent forming quaternary ammonium salts. The alkylation with alkylfluorosulfonates can be catalyzed as other alkylation reactions for increasing the reaction rate. A catalyst that can be used in this reaction is Hg(CN)2.
\nDiazomethane is another common alkylating (methylating) reagent. The alkylation using diazomethane is assumed to take place as follows:
Diazomethane is a gaseous unstable substance, which cannot be stored for long periods of time. It is usually prepared in small quantities and used immediately with or without an intermediate step of dissolution in ether. The preparation can be done from different N-nitroso-N-alkyl compounds in a reaction with a base. A common preparation uses N-nitroso-N-alkyl-p-toluenesulfonamide (Diazald). Methylation with diazomethane may require addition of a Lewis acid catalyst such as BF3. The methylation of partly acetylated sugars and amino sugars using diazomethane and BF3 in ether leads to the methylation of the free OH groups without the migration or substitution of the existent acyl groups.
\nA common alkylation of acidic analytes such as carboxylic acids, phenols, and thiols is performed using another type of alkylating reagent, namely, N,N-dimethylformamide dialkyl acetals. N,N-Dimethylformamide dimethyl acetal (Methyl-8®) is commonly used for methylations. For a compound containing a COOH group, the reaction with this reagent takes place as follows:
The compounds with acidic hydrogens can also be alkylated (methylated) using trimethyl orthoacetate, alkyl-p-tolyltriazenes (R─NH─N═N─C6H4─CH3), and O-alkyl isoureas are also used for the formation of analytes containing acidic hydrogens, imino esters, etc.
\nAlcohols can also act as alkylating reagents in particular when the analyte contains a more acidic hydrogen. Catalyst such as HCl, BF3, CF3 COOH or a cation exchange resin in H+ form is also frequently added to facilitate the reaction. The addition of HCl can be made as a water solution or as gaseous HCl that does not bring additional water to the reaction medium. The formation of alkyl or aryl derivatives of acids is a particularly important reaction known as esterification. Derivatization by esterification has been used with acids as the analyte and the alcohol as the reagent and also with the alcohol as the analyte and the acid the reagent. The esterification can be viewed either as the acid alkylation or as the acylation of the alcohol (see also the esterification mechanism). This reaction is typically catalyzed by strong acids and can be written as follows:
The mechanism of ester formation can be summarized by the following series of reactions:
The esterification efficiency can be improved by removing the water formed in this reaction. This can be done using a chemical reagent or distillation when the compounds of interest boil above 100°C. Among the materials able to eliminate water are desiccants such as anhydrous MgSO4, molecular sieves, or substances that react with water such as CaC2, (CH3)2C(OCH3)2 (2,2-dimethoxypropane), and even an appropriately chosen acid anhydride that reacts faster with water than with the reacting alcohol. The derivatization also may be performed in the presence of SOCl2 (thionyl chloride), which reacts with the water assisting in its removal, and when present in excess, may react with the alcohols forming alkyl chlorides or with the acids forming acyl chlorides. Chloride is a better leaving group in a nucleophilic alkylation reaction, and the efficiency of alkylation increases. Acids also can be esterified using a mixture of an alcohol and an acyl halide.
\nOne procedure for the formation of esters with less active organic acids applies the addition of dicyclohexylcarbodiimide (DCCI) in the derivatization process, to facilitate esterification. The reaction can be performed by adding to the acids that need to be analyzed the appropriate alcohol and DCCI usually in a solvent such as pyridine. Dicyclohexylurea, which is formed in the reaction, is not soluble in pyridine and can be separated. Besides DCCI, other carbodiimides can be used in the reaction of acids and alcohols. Among these are carbonyldiimidazole (CDI), 6-chloro-1-p-chlorobenzensulfonyloxybenzotriazole (CCBBT), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDAC), etc. Also, 2-chloro-1-methylpyridinium iodide, 2,4,6-triisopropylbenzenesulfonyl chloride, trialkyloxonium fluoroborate, etc. can be used to facilitate esterification.
\nTransesterification is another technique applicable for obtaining certain alkyl derivatives of acids (or acyl derivatives of alcohols). The reaction can be written as follows:
Transesterification can be catalyzed by acids (or Lewis acids) such as HCl, BF3, and H2SO4 or by bases such as CH3OK, CH3ONa, or C4H9ONa. The basic catalysts are commonly used for the methanolysis of triglycerides, followed by the analysis of the fatty acid methyl esters using GC or GC/MS [16].
\nA special alkylation can be achieved online during the heating in the injection port of a gas chromatograph using tertraalkylammonium hydroxides or alkylarylammonium hydroxides. Tetramethylammonium hydroxide (TMAH) is the most common reagents of this type. The reaction takes place as follows (Δ indicates heating):
Numerous other reactive compounds may be used for replacing active hydrogens in specific compounds. For example, epoxides, aziridines, and episulfides react easily with compounds with active hydrogens. Formation of a second group containing an active hydrogen may preclude the use of such reagents for analytical purposes.
\nBesides the desired derivatives, certain unexpected compounds that can be considered artifacts for the particular analysis can also be formed in alkylation reactions. The artifacts may be formed from unexpected interactions of the reagent with the analyte or may be a result of undesired effects of the catalysts or medium used for derivatization. In some cases, the control of the alkylation process may be difficult. Longer or shorter reaction times or intervals between derivatization and analysis may lead to errors, even when an internal standard is used for quantitation.
\nOne common case of artifact formation occurs during the reaction with compounds containing O-acyl or N-acyl groups, such as previously acylated carbohydrates, glycolipids, or glycoproteins, in particular when the reaction is done with short-chain alkyl bromides or iodides. When the OH groups of different sugars or NH2 groups of amino sugars were already protected with acyl groups, it was noted that, depending on the catalyst and the chosen medium, these acyl groups can be replaced by alkyl groups, or they may migrate from one position (such as C1) to other positions.
\nOxidation is another common side reaction when using Ag2O as a catalyst. The oxidation effect of Ag2O can be seen on free sugars as well as when attempting to permethylate peptides. Sulfhydryl groups are particularly sensitive to oxidation with Ag2O as a catalyst. The use of methylsulfinyl carbanion as a methylating reagent may also produce undesired side reactions with certain esters generating methylsulfinylketones. Also, strong alkylating reagents may produce undesired artifacts by unexpected alkylations.
\nThe derivatization with the purpose of obtaining aryl derivatives is similar in many respects to the alkylation reaction. The reaction takes place with compounds containing active hydrogens. Simple aryl halides are generally resistant to be attacked by nucleophiles and do not react similar to alkyl halides. This low reactivity can be significantly increased by changes in the structure of aryl halide or in the reaction conditions. The nucleophilic displacement can become very rapid when the aryl halide is substituted with electron attracting groups such as NO2.
\nSilylation is the chemical reaction of replacing a reactive hydrogen atom in OH, COOH, SH, NH, CONH, POH, SOH, or enolisable carbonyl with a silyl group, most frequently with trimethylsilyl (TMS). A large number of analytical methods involve silylation applied to alcohols including carbohydrates [17], phenols [18], amines, sterols [19], etc. The purpose of silylation in chromatography is mainly to reduce the polarity of the analyte, increase its stability, and improve the GC behavior. The differences in the mass spectra of the silylated compounds as compared to the initial analyte may also be an advantage for detectability. However, the mass spectra of many silylated compounds may not be available in common mass spectral libraries. Also, the silylated compounds plus the commonly present excess of silylating reagent may deteriorate some types of stationary phases such as that of Carbowax (polyethylene glycol)-type columns, and for this reason, their separation cannot be done on such columns.
\nSilylation can be performed on specific analytes or directly on complex samples such as a plant material (see, e.g., [12]). The silylating agent and the solvent can play the double role of extractant and silylating reagent. Many publications describe the use of silylation reactions for analytical purposes (e.g., [1, 5, 20]). The reaction of an analyte Y
The molecular weight for TMS is 73.047 calculated considering in the elemental composition of only the masses of the most abundant isotope. Numerous reagents have been synthesized to be used in silylations. Various aprotic solvents can be used as medium for silylation. The analysis can be focused on one analyte or on a mixture of analytes. The main factors contributing to the increase of the efficiency and the rate of the silylation reaction are the silyl donor ability of the reagent and the ease of silylation of different functional groups in the analyte. The solvent (or mixture of solvents) used as a medium and the compounds present or added in the silylation medium may also play a role for silylation efficiency. The reagent excess is sometimes important for displacing the equilibrium in the desired direction, and usually an excess up to ten times larger than stoichiometrically needed is used for silylation. Temperature also increases reaction rate, as expected, and heating of the sample with the reagents at temperatures around 70°C for 15 to 30 min is common. Some reagents used for trimethylsilylation are shown in Figure 8 [14].
\nSome reagents used for trimethylsilylation.
The approximate order of the increasing silyl donor ability for the reagents shown in Figure 8 is HMDS < TMCS < MSA < TMSA < TMSDEA < TMSDMA < MSTFA < BSA < BSTFA < TMSI. This order may be different on particular substrates where other reagents or reagent mixtures may be more reactive.
\nSilylation reagents can be used pure or in mixtures of two or even three reagents. The reagent mixtures may provide a more efficient silylation for specific compounds. For example, silylation of 3,4-dimethoxyphenylethylamine with BSA leads to the substitution of only one active hydrogen in the NH2 group, while the silylation with BSA in the presence of 5% TMCS produces silylation of both hydrogens in the NH2 [21]. A common silylating mixture is BSTFA with 1% TMCS.
\nOne of the determining factors regarding the silylation efficiency is the nature of the molecule Y
Several functional groups that can be silylated (listed in the approximate order of decreasing ease of silylation).
In general, the silylation of OH and COOH groups takes place with better results than that of NH2, CONH, or NH groups. Excellent results are obtained, for example, for the analysis of phenols after silylation [19]. A chromatogram of a solution containing a mixture of phenols at concentrations between 2.0 and 2.5 μg/mL in DMF, derivatized with BSTFA, separated on a BPX-5 chromatographic column (SGE Anal. Sci.), followed by MS analysis in single-ion monitoring (SIM) mode is shown in Figure 9. Details regarding the analyzed phenols are given in Table 3.
\nChromatogram of a set of phenol standards in DMF with the concentrations between 2.0 and 2.5 μg/mL derivatized with BSTFA, separated on a BPX-5 chromatographic column followed by MS analysis.
No. | \nCompound | \nRet. time | \nm/z | \nAbrrev. | \nNo. | \nCompound | \nRet. time | \nm/z | \nAbrrev. | \n
---|---|---|---|---|---|---|---|---|---|
(1) | \nPhenol | \n6.88 | \n166 | \nPh | \n(14) | \n3,4-Dimethylphenol | \n12.32 | \n194 | \n3,4-diMePh | \n
(2) | \no-Cresol | \n8.57 | \n180 | \no-Cr | \n(15) | \n3-Methoxyphenol | \n13.17 | \n196 | \n3-MeOPh | \n
(3) | \nm-Cresol | \n8.76 | \n180 | \nm-Cr | \n(16) | \n4-Methoxyphenol | \n13.47 | \n196 | \n4-MeOPh | \n
(4) | \np-Cresol | \n9.08 | \n180 | \np-Cr | \n(17) | \nCatechol | \n13.88 | \n254 | \nCa | \n
(5) | \n2-Ethylphenol | \n10.28 | \n194 | \n2-EtPh | \n(18) | \nResorcinol | \n16.05 | \n254 | \nRe | \n
(6) | \n2,5-Dimethylphenol | \n10.70 | \n194 | \n2,5-diMePh | \n(19) | \n4-Methylcatechol | \n16.27 | \n268 | \n4-MeCa | \n
(7) | \n3,5-Dimethylphenol | \n11.07 | \n194 | \n3,5-diMePh | \n(20) | \nHydroquinone | \n16.73 | \n254 | \nHy | \n
(8) | \n2,4-Dimethylphenol | \n11.20 | \n194 | \n2,4 diMePh | \n(21) | \n3-Methylcatechol | \n16.71 | \n268 | \n3-MeCa | \n
(9) | \n2-Methoxyphenol | \n11.28 | \n196 | \n2-MeOPh | \n(22) | \n5-Methylresorcinol | \n18.19 | \n268 | \n5-MeCa | \n
(10) | \n4-Ethylphenol | \n11.59 | \n194 | \n4-EtPh | \n(23) | \n2-Methylresorcinol | \n18.66 | \n268 | \n2-MeRe | \n
(11) | \n4-Chlorophenol | \n11.71 | \n185 | \n4-ClPh | \n(24) | \n4-Ethylresorcinol | \n19.90 | \n282 | \n4-EtRe | \n
(12) | \n2,6-Dimethylphenol | \n11.79 | \n194 | \n2,6-diMePh | \n(25) | \n2,5-Dimethylresorcinol | \n20.18 | \n282 | \n2,5-diMeRe | \n
(13) | \n2,3-Dimethylphenol | \n12.02 | \n194 | \n2,3-dimePh | \n\n | \n | \n | \n | \n |
Details regarding the analyzed phenols with the chromatogram shown in Figure 9.
Besides organic active hydrogens, several inorganic compounds with active hydrogens can also react with silylating reagents. Among these are H2O, H2O2, and strong inorganic acids. Also, some salts of the acids may be silylated. The reaction of silylating reagents with water imposes that water should be at the low level in the matrix or the solution of the analytes. The reaction with water takes place as follows:
In many solvents used as medium for derivatization, the trimethylsilanol formed in the reaction with water is separated as a distinct layer of solvent. The formation of two layers impedes a proper sampling of the derivatized material in the GC/MS instrument. In addition to that, the presence of an excess of water suppresses the derivatization of other compounds. The silylation is not recommended on samples with a water content higher than about 10%.
\nThe silylation reaction is commonly performed in a solvent that does not have active hydrogens. The most commonly used solvents as a medium for silylation are dimethylformamide (DMF), pyridine, and acetonitrile. The main role of the solvent is to dissolve the analyte and the reagents. The by-product HX of silylation shown in reaction (17) can be an acid, a base, or a neutral compound. As examples, for TMCS the by-product is HCl, for HMDS the by-product is NH3, for BSTFA the by-product is N-TMS-trifluoroacetamide, and for TMSI the by-product is imidazole. When the silylation reagent generates an acid as a by-product of the reaction, this may interfere with the silylation. For this reason, silylation can be promoted by any acid acceptor used as solvent or present in the solvent. Among such solvents are pyridine, triethylamine, and to a lower extent DMF. They can be used as both solvents and acid acceptors. Mixtures of solvents are commonly used for both enhancing solubility and promoting silylation. For example, formamide in the presence of pyridine may react with an acidic by-product generating CO and an ammonium salt. The addition of basic compounds to the silylation reaction may also influence the efficiency of the silylation. Also, some compounds may act as catalysts for silylation.
\nAlthough the TMS derivatives are by far the most commonly used in the derivatization for analytical purposes, other substituents in the silyl group can be used as reagents. Several such groups are indicated in Figure 10. The groups can be present in a variety of reagents connected to leaving groups “X-” such as Cl-, imidazolyl, F3C-(CO)-N(CH3)-, etc. For example, a common reagent containing
Examples of silyl groups different from TMS used in silylation reagents.
The use of different groups than TMS may serve different purposes. For example, a fluorinated or brominated group may enhance significantly the detection sensitivity when using ECD or NCI-MS. Also, the stability toward hydrolysis of compounds silylated with different groups than TMS may be higher, and such silylation can be advantageous. This is, for example, the case of
As an example, silylation of amino acids with MTBSTFA is commonly used [22, 23], and it is preferred to the silylation generating TMS derivatives. The chromatogram of a set of amino acid standards with the concentration of 0.05 μmol/mL derivatized with MTBSTFA and separated on a DB-5MS chromatographic column (from Agilent) followed by MS analysis is shown in Figure 11. Details regarding the analyzed amino acids are given in Table 4.
\nChromatogram of a set of amino acid standards with the concentration of 0.05 μmol/mL derivatized with MTBSTFA separated on a DB-5MS chromatographic column.
Peak No. | \nAmino acid | \nAbbrev. | \nMW | \nFormula + x TBDMS | \nMW + x TBDMS | \nCharact. ion | \nRet. time | \n
---|---|---|---|---|---|---|---|
(1) | \nα-Alanine | \nα-Ala | \n89.09 | \nC15H35NO2Si2 | \n317 | \n260 | \n31.69 | \n
(2) | \nGlycine | \nGly | \n75.07 | \nC14H33NO2Si2 | \n303 | \n246 | \n32.63 | \n
(3) | \nSarcosine | \nSar | \n89.09 | \nC15H35NO2Si2 | \n317 | \n260 | \n33.85 | \n
(4) | \nα-Amino-n-butyric acid | \nα-ABu | \n103.10 | \nC16H37NO2Si2 | \n331 | \n274 | \n34.36 | \n
(5) | \nβ-Alanine | \nβ-Ala | \n89.09 | \nC15H35NO2Si2 | \n317 | \n260 | \n35.58 | \n
(6) | \nUrea | \n\n | 60.06 | \nC13H32N2OSi2 | \n288 | \n231 | \n36.01 | \n
(7) | \nβ-Aminoisobutyric acid | \nβ-ABu | \n103.10 | \nC16H37NO2Si2 | \n331 | \n274 | \n36.11 | \n
(8) | \nValine | \nVal | \n117.15 | \nC17H39NO2Si2 | \n345 | \n186 | \n36.15 | \n
(9) | \nLeucine | \nLeu | \n131.17 | \nC18H41NO2Si2 | \n359 | \n200 | \n37.71 | \n
(10) | \nNorleucine | \n\n | 131.17 | \nC18H41NO2Si2 | \n359 | \n200 | \n38.8 | \n
(11) | \nIsoleucine | \niLeu | \n131.17 | \nC18H41NO2Si2 | \n359 | \n200 | \n38.8 | \n
(12) | \nγ-Aminobutyric acid | \nγ-ABu | \n103.10 | \nC16H37NO2Si2 | \n331 | \n274 | \n39.79 | \n
(13) | \nProline | \nPro | \n115.13 | \nC17H37NO2Si2 | \n343 | \n184 | \n39.87 | \n
(14) | \n2-Phenylglycine | \nPhGly | \n151.17 | \nC20H37NO2Si2 | \n379 | \n220 | \n46.16 | \n
(15) | \n5-Oxoproline | \noPro | \n129.13 | \nC17H35NO3Si2 | \n357 | \n300 | \n46.18 | \n
(16) | \nMethionine | \nMet | \n149.20 | \nC17H39NO2SSi2 | \n377 | \n320 | \n46.68 | \n
(17) | \nSerine | \nSer | \n105.09 | \nC21H49NO3Si3 | \n447 | \n390 | \n47.52 | \n
(18) | \nThreonine | \nThr | \n119.12 | \nC22H51NO3Si3 | \n461 | \n404 | \n48.43 | \n
(19) | \nPhenylalanine | \nPhe | \n165.19 | \nC21H39NO2Si2 | \n393 | \n336 | \n50.35 | \n
(20) | \nAspartic acid | \nAsp | \n133.10 | \nC22H49NO4Si3 | \n475 | \n418 | \n52.47 | \n
(21) | \nHydroxyproline | \nHyPro | \n131.13 | \nC23H51NO3Si3 | \n473 | \n314 | \n53.23 | \n
(22) | \n3-Methyl-L-histidine | \n3MeHys | \n169.20 | \nC19H39N3O2Si2 | \n397 | \n340 | \n55.15 | \n
(23) | \nGlutamic acid | \nGlu | \n147.13 | \nC23H51NO4Si3 | \n489 | \n432 | \n55.53 | \n
(24) | \nOrnithine | \nOrn | \n132.20 | \nC23H54N2O2Si3 | \n474 | \n286 | \n55.64 | \n
(25) | \n1-Methyl-L-histidine | \n1MeHys | \n169.20 | \nC19H39N3O2Si2 | \n397 | \n302 | \n57.03 | \n
(26) | \nLysine | \nLys | \n146.19 | \nC24H56N2O2Si3 | \n488 | \n300 | \n58.02 | \n
(27) | \nα-Aminoadipic acid | \n\n | 161.20 | \nC24H53NO4Si3 | \n503 | \n446 | \n58.06 | \n
(28) | \nHistidine | \nHys | \n155.16 | \nC24H51N3O2Si3 | \n497 | \n440 | \n62.29 | \n
(29) | \nTyrosine | \nTyr | \n181.19 | \nC27H53NO3Si3 | \n523 | \n302 | \n63.29 | \n
(30) | \nArginine | \nArg | \n174.20 | \nC24H56N4O2Si3 | \n516 | \n144 | \n64.26 | \n
(31) | \nTryptophan | \nTrp | \n204.22 | \nC29H54N2O2Si3 | \n546 | \n244 | \n67.98 | \n
(32) | \nCystine | \nCys | \n240.30 | \nC28H64N2O4S2Si4 | \n668 | \n348 | \n72.65 | \n
(33) | \nHomocystine | \nhCys | \n268.30 | \nC32H72N2O4S2Si4 | \n724 | \n362 | \n76.59 | \n
Details regarding the analyzed amino acids with the chromatogram shown in Figure 11.
In most situations, silylation generates only the desired derivatives. However, there are cases when the expected silylated compound is not formed, and either the silylation is not complete, or some compounds such as aldehydes, ketones, or esters with no obvious active hydrogen generate silylated compounds. Incomplete silylation is usually the result of inappropriate reaction conditions. However, when compounds with multiple functionalities are silylated, it is possible to generate a variety of derivatized compounds, regardless of the intention to obtain fully silylated or partly silylated compounds.
\nIn some cases, artifacts are formed due to the modification of the analyte under the influence of the reagents during derivatization. For example, when the silylation is done in basic or acidic conditions, the analytes that are sensitive to acidic or basic media may suffer unexpected transformations. The most frequent artifacts with compounds not containing obvious active hydrogens occur with aldehydes. Some aldehydes are able to undergo two types of chemical reactions with formation of OH groups, namely, enolization and acetal formation in the presence of water. The OH groups formed in this manner react with different silylating reagents and give the corresponding silylated products. Although the enolization or the acetal formation is negligible for the initial aldehyde, the reactions may be significantly displaced toward the formation of the silylated compounds of the enol or of the acetal. Artifacts can also be generated when the reaction is allowed to continue for an extended period of time. Other uncommon reactions with a specific silylation reagent and analyte may occur. An example of an uncommon reaction is the ring opening of flavanones.
\nThe formation of acyl derivatives is applied for replacing the active hydrogens from an analyte in functionalities such as OH, SH, NH [11, 24], CONH, etc. The acylation is also used for reducing polarity and improving the behavior of the analytes in the chromatographic column. Acylation may confer a better volatility of the analytes, although not as marked as for silylation or methylation. Only the derivatization with acetyl groups or with fluorinated acyl groups (not heavier than heptafluorobutyryl) improves volatility, while other heavier acyl groups are not suitable for this purpose. Acetylation, for example, can be used for compounds such as monosaccharides and amino acids to allow GC analysis. The detectability improvement on the other hand is a very common purpose for acylation. Acylation with fluorinated compounds is frequently used for enhancing detectability in GC with ECD or NCI-MS detection. Other uses of acylation include the enhancement of separation of chiral compounds, etc.
\nMost acylation reactions are nucleophilic substitutions where the analyte is a nucleophile (Y
Some common acyl groups present in acylation reagents are indicated in Table 5.
\nSome common groups present in acylating reagents used in derivatizations for GC analysis [14].
As shown in Table 5, the acyl groups in the reagent can be attached to various “X” groups. One such group is OH and among the acylating reagents are some free acids. When nucleophile is an alcohol, the reaction is known as esterification and has been discussed in Section 7. The acylation with acids can be applied besides alcohols to certain thiols, phenols, amines, etc. and can be written as follows:
The reaction can be displaced toward the formation of the acyl derivatives by eliminating the water using compounds such as anhydrous MgSO4, molecular sieve, or substances that react with water such as CaC2, or (CH3)2C(OCH3)2. Dicyclohexylcarbodiimide (DCCI) also is used for modifying the yield of the desired product. The reaction with reagents containing a carboxylic acid reactive group also can be done in the presence of 2,4,6-trichlorobenzoyl chloride or with various sulfonyl chlorides such as 2,4,6-triisopropyl-benzenesulfonyl chloride or 2,4,6-trimethyl-benzenesulfonyl chloride. The reaction of amines with acids can be displaced toward the formation of the amides using a peptide coupling reagent such as benzotriazol-1-yl-oxy-tris(dimethyl-amino)-phosphonium hexafluorophosphate (BOP), diethyl cyanophosphonate, O-benzotriazol-1-yl-N,N,N′,N′-bis(tetramethylene)uronium hexafluorophosphate, 2,2′-dipyridyl disulfide + triphenylphosphine, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDAC), etc.
\nCommon acylating reagents are acyl halides such as chlorides or bromides, which are reactive compounds suitable for acylation. The reaction of an acyl chloride with an amine, for example, takes place as follows:
Since the reactivity of amides is lower than that of amines, the second hydrogen in the amine is more difficult to replace. Also, steric hindrance may negatively influence the reaction. The generation of a strong acid such as HCl is a disadvantage in the reaction with acyl halides, and usually the acid should be removed either by adding basic compounds such as Na2CO3 or MgCO3 or using pyridine as the reaction medium. The high reactivity of acyl halides is used for the acylation of compounds with less reactive hydrogens. Certain carbonyl cyanides react similarly to acyl chlorides.
\nThe disadvantage of generating a strong inorganic acid in the acylation with acyl halides also can be avoided by having, instead of the acyl halide, an anhydride. The reaction of Y
The acid resulting together with the acylated compound is not a strong acid such as HCl. The anhydrides of trifluoroacetic acid (TFA), pentafluoropropionic anhydride (PFPA), and heptafluorobutyric (HFBA) acids are commonly used for derivatization of alcohols, phenols, amines, etc., with the purpose of enhancing detectability (by ECD or NCI-MS) and also for improving the chromatographic behavior (higher volatility, better thermal stability, better separation). The volatility of fluorinated compounds allows the GC applications. The reactivity of the perfluorinated anhydrides increases in the order HFBA < PFPA < TFA. However, the differences are not significant. Once formed, the heptafluorobutyrates are more stable to hydrolysis than the trifluoroacetates. An inert solvent such as CH2Cl2, ether, ethyl acetate, acetone, tetrahydrofuran or in CH3CN, etc. can be used as a medium for the reaction with perfluoroanhydrides. For the neutralization of the acids formed during derivatization, the basic compounds such as triethylamine, pyridine, or even solid NaHCO3 can be utilized.
\nIn order to avoid the formation of water or of a strong acid in the acylation reaction, certain amides such as N-methyl-bis(trifluoroacetamide), bis(trifluoroacetamide), or 2,2,2-trifluoro-N-methyl-N-(2,2,2-trifluoroacetyl)acetamide (MBTFA) can be used as reagents. Acylation of amines takes place at room temperature. Solvents such as CH3CN, pyridine, DMSO, or THF can be used as a reaction medium:
One other procedure successfully applied to obtain acyl derivatives is the use of acyl imidazoles as reagents. This class of compounds reacts with analytes containing alcohol, primary and secondary amino groups, or thiols. The reaction generates as a by-product imidazole:
Succinimidyl esters also can be used for acylation purposes. Amines and the amino group in amino acids also can be acylated using urethane-protected α-amino acid-N-carboxyanhydrides or oxycarbonyl-amino acid-N-carboxyanhydrides. Alkylketenes and their dimers may be used for acylation.
\nA special type of acylation is that using chloroformates. Carbonic acid, O═C(OH)2, can form amides, esters, halides, etc., due to the presence of two OH groups bonded to the CO group. Carbonic acid ester halides, also called chloroformates or chloroformate esters, with the formula R─O─C(═O)─X, where R is an alkyl or aryl group and X is F, Cl, Br, or I, can react with various compounds containing active hydrogens, such as acids [25], amines, alcohols, thiols, and amino acids. Amino acids, for example, in the presence of an alcohol in water form carbamate esters (urethanes) reacting as follows [26]:
The formation in reaction (25) of the alcohol Ra–OH may lead to traces of a resulting compound with both substituted radicals being Ra. For this reason it is typically recommended to perform the reaction in the presence of an alcohol having the same radical as the chloroformate reagent (Ra = Rb). Chloroformates containing in the alkyl or aryl group halogen substituents are particularly reactive. Even tertiary amines can react with specific chloroformates, such as pentafluorobenzoyl chloroformate or with trichloroethyl chloroformate, by displacing an alkyl group connected to the nitrogen atom and forming the carbamate ester.
\nSimilar in many respects to that of acyl derivatives R–CO–X are the reactions of sulfonyl derivatives R–SO2–X. Sulfonyl halides are in general less reactive than halides of carboxylic acids. The reaction of a sulfonyl derivative may take place with alcohols, phenols, amines, etc. The reactivity toward the sulfonyl sulfur is RNH2 > CH3COOR > H2O > ROH.
\nHigh reactivity toward active hydrogens in alcohols, amines, etc. can also be achieved using reagents with other functionalities. These functionalities include isocyanates, isothiocyanates, carbonyl azides, etc. These reactions can be seen as a replacement of an active hydrogen with a CO-R group or CS-R group as it occurs in other acylations.
\nA variety of other derivatization reactions are reported in the literature (see, e.g., [1]) and used for GC and GC/MS analyses. Among these are the addition to hetero multiple bonds in functional groups such as C═O, C═S, C═N, or C☰N. Many such reactions are additions to multiple bonds. Such reactions are, for example, the additions to the C═O groups in aldehydes and ketones. Reagents containing active hydrogens in groups such as NH2, OH, H2N-NH-, etc. can react, for example, with aldehydes and ketones. Alcohols, for example, form hemiacetals or acetals with aldehydes and ketals with ketones, and although most of such compounds are not stable enough to be suitable for derivatization, cyclic acetals and ketals may be stable and used for analytical purposes. A common reaction of carbonyl compounds is with amines. The initial addition reaction usually continues with water elimination forming a substituted imine or a Schiff base. Similar to the reaction of amines is the reaction with substituted hydroxylamines or hydrazines. A typical reaction of derivatization of carbonyl compounds is that using dinitrophenylhydrazine (DNPH). The derivatized compound can be analyzed either by LC [27] or by GC/MS [28]. The reaction takes place as follows:
The groups Ra and Rb can be H or alkyl or various other substituents.
\nAnother reagent that can be used for ketone derivatization is N-aminopiperidine in the presence of catalytic amounts of acetic acid. The resulting substituted hydrazone can be used in GC analysis:
β-Diketones may react differently with hydrazines generating pyrazole derivatives as shown below:
Several other classes of compounds similar to hydrazines react with the carbonyl compounds. Among these are hydrazones (NH2─N═CR2), hydrazides (NH2NH-COR), and semicarbazide (NH2NH-CONH2). Hydroxylamines also react with carbonyl compounds forming oximes. Hydroxylamine itself, hydroxylamine hydrochloride (STOX® reagent), or derivatives such as H2N-OSO3H in a solvent like pyridine can be used in this reaction:
When the reaction is performed with hydroxylamine, the generated oxime contains an active hydrogen. This can be further derivatized, for example, by silylation in a reaction with a common silylation reagent.
\nFor derivatization purposes other reagents can be used, such as substituted hydroxylamines like methoxyamine hydrochloride NH2OCH3•HCl (MOX® reagent) and O-(pentafluorobenzyl)-hydroxylamine hydrochloride (FLOROX® reagent). The reaction of a ketone or aldehyde with FLOROX is shown below:
The oximes existing in
The transformation of the oximes into nitriles generates one single compound from the two (syn- and anti-) isomers and can be used to simplify the chromatograms of sugars derivatized as oximes.
\nAlcohols, amines, and thiols also can react at other hetero multiple bonds leading to analytical applications. This addition may occur at the isocyanates (─N═C═O), ─C═O group in an amide, at a nitrile, at CS2, or at other groups. One example is the addition under special conditions of alcohols to dimethylformamide. The resulting acetals are very reactive and are used themselves as reagents, as shown previously for N,N-dimethylformamide dimethyl acetal (see reaction 12). Another example is the reaction of CS2 with alcohols in the presence of a base, leading to the formation of xanthates. Amines also react with CS2, and the formed isothiocyanate can be analyzed using GC analysis. The reaction takes place as follows:
Formation of new cycles from noncyclic compounds or replacement of old cycles with new ones that are more stable or have a desired property is also exploited in sample processing using derivatization. Epoxides, for example, can be formed in the reaction of a compound with a carbon–carbon double bond and a peroxy acid. Among the peroxy acids more frequently used for the formation of epoxides are peracetic, performic, perbenzoic, trifluoroperacetic, and 3,5-dinitroperoxybenzoic acids. However, in this reaction a mixture of enantiomers is formed, as shown below for a
The separation of the epoxides may be easier to achieve than that of olefins, and this type of derivatization has been utilized, for example, for better separation of various
Another reaction with formation of new cycles is that of amino acids with phenyl isothiocyanate leading to a thiohydantoin derivative:
This reaction has been successfully used for the analysis of amino acids in proteins [29, 30].
A variety of aromatic cycles can be formed in reactions involving bifunctional compounds. Addition reactions to hetero multiple bonds in bifunctional molecules frequently lead to cyclic compounds. For example, formaldehyde can react with tryptophan or tryptamine generating a β-carboline derivative as follows:
The new compound can be analyzed by GC, usually after further derivatization by silylation of the carboxyl group.
\nA typical reaction leading to pyrazoles is the reaction of hydrazines with diketones such as 2,4-pentandione (acetylacetone). For example, the reaction between hydrazine or methylhydrazine and acetylacetone takes place as follows:
Activated carbonyl groups such as those in hexafluoroacetone are known to react with difunctional compounds. The reaction may take place with an amino acid as follows:
Amino acids can react with an activated anhydride such as trifluoroacetic anhydride (TFAA):
The reaction takes place by heating the amino acids with an excess of TFAA. The reaction mixture is then dissolved in ethyl acetate and analyzed by GC.
\nNumerous other types of derivatization reactions were used for making the analytes suitable for GC and GC/MS analyses. These include formation of various cyclic types of compounds such as azines, siliconides, boronates, etc., that are thermally stable and do not have polar hydrogens such that GC or GC/MS analysis is possible. In addition to reagents that add specific moieties to the analytes, oxidation and reduction were sometimes used for the analyte modification (see, e.g., [4]).
\nSolid-phase reagents are polymeric materials with specific groups that are reactive and can be transferred to the analyte molecule producing derivatization. For an analyte of the form Y
Solid-phase reagents must work analogously to the corresponding small-molecule reagents containing the group R (a tag). Reagents that are insoluble in certain solvents at high concentrations can often provide a high ratio of analyte/substrate in a polymeric microenvironment that yields a high kinetic rate for the heterogeneous reaction.
\nA variety of materials can be used as solid support, such as specifically bound reagents on a silica support (used, e.g., for online derivatization in HPLC analysis), ion exchange resins, as well as other supports [31]. One example of solid-phase support that can produce derivatization is trifluoroacetyl nylon 6,6. This solid-phase reagent can be obtained from poly(hexamethylene adipamide) (nylon 6,6) and trifluoroacetyl anhydride. This solid-phase reagent can be used in amine derivatization in a reaction as follows:
This derivatization of the amine is done by mixing the solid-phase reagent with a solution of amine solution in CH3CN. Following derivatization, the solid-phase reagent is separated by centrifugation, and the solution is concentrated by evaporating part of the solvent and analyzed by GC (an amine internal standard must be used in this procedure). However, some such derivatizations require a long time of interaction between the solid-phase reagent and the analytes and found only limited applications.
\n(Another) alternative of derivatization of specific analytes is using the reaction between the reagent and the analyte both adsorbed on a solid support. This type of derivatization has been used, for example, in connection with a solid-phase microextraction (SPME) technique [32]. In this technique a reagent is initially adsorbed in the SPME fiber, followed by exposure to the analytes. The derivatized analytes are further desorbed in the injection port of the GC and analyzed using a detector such as MS. For example, formaldehyde from air can be analyzed using a polydimethylsiloxane (PDMS) fiber containing
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\n\nCURRENT PROJECTS
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