Selected Imidazole Derivatives: Synthesis and X-Ray Crystal Structure – A Review

Abstract

This chapter accounts for the synthesis and X-ray structure of selected imidazole derivatives: DMDPIMH: 4,5-dimethyl-1,2-diphenyl-1H-imidazole monohydrate, DMPPTI: 4,5-dimethyl-2-phenyl-1-(p-tolyl)-1H-imidazole, FPDMMPI: 2-(4-fluorophenyl)-4,5-dimethyl-1-(4-methylphenyl)-1H-imidazole, DMPDMPIHH: 1-(3,5-dimethylphenyl)-4,5-dimethyl-2-phenyl-1H-imidazole hemihydrate, DMPFPDMI: 1-(3,5-Dimethylphenyl)-2-(4-fluorophenyl)-4,5-dimethyl-1H-imidazole, FPMOPDMI: 2-(4-fluorophenyl)-1-(4-methoxyphenyl)-4,5-dimethyl-1H-imidazole, DMOPFPDMI: 1-(3,5-dimethoxyphenyl)-2-(4-fluorophenyl)-4,5-dimethyl-1H-imidazole, and FPTPI: 2-(4-fluorophenyl)-1,4,5-triphenyl-1H-imidazole. The molecular crystal structure was determined by this investigation, along with the impact of substitutions on the geometry of the imidazole units. The uses and applications of the imidazole compounds are described in the introduction. All eight imidazole derivatives’ syntheses were discussed. The essential characteristics of the imidazole derivatives are provided by the structural analyses of the eight derivatives and a portion of a database survey. All the derivatives have a planar imidazole unit. The crystal structures are stabilized by intermolecular O▬H…N, O▬H…O, C▬H…N, hydrogen bonds, and C▬H…π interactions.

1. Introduction

An online search reveals that C₃N₂H₄ is the formula for the chemical molecule imidazole. A solid that is either colorless or white and water-soluble only slightly produces an alkaline solution. It is a diazole and an aromatic heterocycle in a chemical sense since it has meta-substituted nitrogen atoms that are not contiguous. Imidazole was named in 1887 by the German chemist Arthur Rudolf Hantzsch (1857–1935) [1].

Because of their ability to fluoresce and glow under certain conditions, imidazoles are widely used in analytical processes [2]. The noticeable alteration in fluorescence following metal binding is a crucial characteristic that makes imidazole derivatives more desirable as a chelator [3]. As a result, extremely sensitive fluorescent chemisensors for sensing and imaging metal ions have been built using imidazole derivatives [4]. Its chelates, especially those that include Ir3⁺, are crucial parts of organic light-emitting diodes and are excellent candidates for fluorescent chemisensors for metal ions [5].

Chemical compounds with an imidazole ring system have many pharmacological properties and play indispensable roles in biochemical processes [6]. Lots of the substituted imidazoles are known as inhibitors of fungicides and herbicides, plant growth regulators, and therapeutic agents. Modern advancements in green chemistry and organometallic chemistry have broadened the limit of imidazoles to the synthesis and application of a prominent category of imidazoles as ionic liquids and imidazole-associated N-heterocyclic carbenes. Imidazole derivatives are also applied as possible anticancer agents. Lately, heterocyclic imidazole derivatives have drawn attention due to their unique optical properties. These compounds play a particularly substantial part in chemistry as mediators for synthetic reactions and the development of functionalized materials. The amino acid histidine, vitamin B12, a component of DNA base structure, purines, histamine, and biotin are just a few examples of well-known components of human bodies that contain the imidazole core. Other examples include azomycin, cimetidine, and metronidazole [7]. The use of imidazole-based compounds was reported for multidrug-resistant tuberculosis, antifungal and antimycobacterial activity, and bactericidal effects [8].

The most essential technique for determining the relative atomic locations in a molecule structure is X-ray diffraction. Additionally, it can offer objective proof of the dimensions and geometry of molecules. The stability of a structure is aided by hydrogen bonds. As a result, it is a component of molecular conformation in that symmetry, and the subsequent arrangement of the molecules should result in the production of as many hydrogen bonds as feasible [9]. This chapter describes the author’s work on the synthesis and crystal structure determination of a few significant novel imidazole derivatives.

2. Imidazole derivatives: synthetic process

2.1 Synthesis of 4,5-dimethyl-1,2-diphenyl-1H-imidazole monohydrate (C₁₇H₁₆N₂.H₂O): DMDPIMH

In 10 ml of ethanol, at a constant temperature of 333 K, 15 mmol of benzaldehyde, 15 mmol of pure butane-2,3-dione, 15 mmol of aniline, and 15 mmol of ammonium acetate were added over the course of an hour. The reaction mixture was refluxed for seven days before dichloromethane extraction was used to complete the process. Using column chromatography (CC), the solid is separated and purified as the eluent (hexane: ethyl acetate). The yield was 1.79 g or 48% (Figure 1). A suitable single crystal was used to collect the X-ray diffraction data [10].

Figure 1.

Schematic diagram for the synthesis of 2.1–2.8.

2.2 Synthesis of 4,5-dimethyl-2-phenyl-1-(p-tolyl)-1H-imidazole (C₁₈H₁₈N₂): DMPPTI

Over about an hour, at a constant temperature of 333 K, 15 mmol of pure butane-2,3-dione, 15 mmol of p-toluidine, 15 mmol of ammonium acetate, and 15 mmol of benzaldehyde were added to 10 ml of ethanol. The actions that follow are completed in the manner outlined in DMDPIMH. The yield was 1.93 g or 46% (Figure 1). An appropriate single crystal was used to acquire the X-ray diffraction data [11].

2.3 Synthesis of 2-(4-fluorophenyl)-4,5-dimethyl-1-(4-methylphenyl)-1H-imidazole (C₁₈H₁₇FN₂): FPDMMPI

For an hour, at a steady temperature of 333 K, 15 mmol of pure biacetyl in 10 ml of ethanol, 15 mmol of p-toluidine, 15 mmol of ammonium acetate, and 15 mmol of p-fluorobenzaldehyde were added. The actions that follow are completed in the manner outlined in DMDPIMH. The yield was 1.93 g or 46% (Figure 1). A suitable single crystal was used to collect the X-ray diffraction data [12].

2.4 Synthesis of 1-(3,5-dimethylphenyl)-4,5-dimethyl-2-phenyl-1H-imidazole hemihydrate (C₁₉H₂₀N₂.0.5H₂O): DMPDMPIHH

15 mmol of pure butane-2,3-dione in 10 ml of ethanol was combined with 15 mmol of 3,5-xylidine, 15 mmol of ammonium acetate, and 15 mmol of benzaldehyde for an hour at a constant temperature of 333 K. The subsequent steps are conducted in the manner specified in DMDPIMH. The yield was 1.91 g or 46% (Figure 1). The X-ray diffraction data were gathered with a suitable single crystal [13].

2.5 Synthesis of 1-(3,5-dimethylphenyl)-2-(4-fluorophenyl)-4,5-dimethyl-1H-imidazole (C₁₉H₁₉FN₂): DMPFPDMI

15 mmol of 3,5-xylidine, 15 mmol of ammonium acetate, and 15 mmol of 4-fluorobenzaldehyde were added to 15 mmol of pure butane-2,3-dione in 10 ml of ethanol for about 1 hour at a constant temperature of 333 K. The remaining procedure is followed as given in DMDPIMH. The yield was 2.1 g or 48% (Figure 1). Crystals suitable for X-ray diffraction studies were developed by slow solvent evaporation using dichloromethane [14].

2.6 Synthesis of 2-(4-fluorophenyl)-1-(4-methoxyphenyl)-4,5-dimethyl-1H-imidazole (C₁₈H₁₇FN₂O): FPMOPDMI

15 mmol of p-anisidine, 15 mmol of ammonium acetate, and 15 mmol of 4-fluorobenzaldehyde were added to 15 mmol of pure biacetyl in 10 ml of ethanol for about 1 hour at a constant temperature of 333 K. The subsequent steps are specified in DMDPIMH. The yield was 1.77 g or 40% (Figure 1). The X-ray diffraction data were gathered using an appropriate single crystal [15].

2.7 Synthesis of 1-(3,5-dimethoxyphenyl)-2-(4-fluorophenyl)-4,5-dimethyl-1H-imidazole (C₁₉H₁₉FN₂O₂): DMOPFPDMI

Pure butane-2,3-dione in 10 ml of ethanol, 3,5-dimethoxyaniline, ammonium acetate, and 4-fluorobenzaldehyde were added in 15 mmol increments over an hour at a constant temperature of 333 K. The remaining actions were completed by the guidelines in DMDPIMH. 2.20 g or 45% of the total were yielded (Figure 1). Crystals suitable for X-ray diffraction measurements were made using dichloromethane as a slow solvent to evaporate [16].

2.8 Synthesis of 2-(4-fluorophenyl)-1,4,5-triphenyl-1H-imidazole (C₂₇H₁₉FN₂): FPTPI

Over an hour at a constant temperature of 333 K, 15 mmol of aniline, 15 mmol of ammonium acetate, and 15 mmol of p-fluorobenzaldehyde were added to 15 mmol of benzil in 10 ml of ethanol. The actions that follow are completed in the manner outlined in DMDPIMH. The yield was 3.51 g or 60% (Figure 1). The X-ray diffraction data were gathered using a suitable single crystal [17].

3. Eight imidazole derivatives: structural analyses

3.1 Structural analysis of 4,5-dimethyl-1,2-diphenyl-1H-imidazole monohydrate (DMDPIMH)

This section shows the structure details of DMDPIMH [10]. SIR2004 [18] solved the structure by using direct methods. SHELXL97 [19] refined the final crystal structure model.

This compound belongs to the tetragonal crystal system with the space group I4₁/a. Molecular formula: C₁₇H₁₆N₂.H₂O; molecular weight: 266.33; crystal data: a = b = 25.5498 Å; c = 9.3792 (1) Å; α = β = γ = 90°; V = 6122.67 (9) ų; Z = 16; D_x = 1.156 Mg m⁻³; F(000) = 2272; final R[F² > 2σ(F²)] = 0.043 and wR(F²) = 0.134 for 2610 reflections observed with I > 2σ(I).

In multiple Fourier maps, the water atoms H1W and H2W coupled to the oxygen atom O1W were found and freely refined. With C▬H = 0.93–0.96 Å; U_iso(H) = kU_eq(C), where k = 1.5 for ▬CH₃ and 1.2 for the other H atoms, the other hydrogen atoms were positioned geometrically and supported by their parent atoms. The ▬CH₃ groupings are disorganized over two locations. Each was enhanced as an idealized disordered ▬CH₃ group.

In this compound (Figure 2), with a maximum deviation of 0.0037 (7) Å for C5, the imidazole ring is planar. The imidazole ring makes dihedral angles of 80.74 (7) and 41.62 (7) ° with the ring (C11▬C16) and the ring (C21▬C26), respectively. 75.83 (8) ° is the dihedral angle among the phenyl rings. Intermolecular hydrogen bonds O1W▬H1W⋯N3 (y + 1/4, −x + 1/4, z + 1/4) and O1W—H2W⋯O1W (y + 1/4, −x + 1/4, z + 1/4) are found in the crystal structure (Figure 3).

Figure 2.

The thermal displacement ellipsoid plot [20] is shown at a 30% probability level.

Figure 3.

The crystal packing with hydrogen bonds [21], viewed along the c-axis.

The ORTEP-3 for Windows drew the thermal displacement ellipsoid plot with a 30% probability level [20] (Figure 2). The crystal packing using the PLATON [21] was viewed along the c-axis (Figure 3).

3.2 Structural analysis of 4,5-dimethyl-2-phenyl-1-(p-tolyl)-1H-imidazole (DMPPTI)

This section depicts the structure details of DMPPTI [11]. The crystal structure was solved by direct methods using the program SIR2002 [22]. The program SHELXL97 [19] refines the final crystal structure model.

This compound belongs to the monoclinic crystal system with the space group P2₁/n. Molecular formula: C₁₈H₁₈N₂; molecular weight: 262.34; crystal data: a = 9.6971 (3) Å; b = 7.5458 (2) Å; c = 19.8407 (7) Å; β = 96.604 (3)°; V = 1442.16 (8) ų; Z = 4; D_x = 1.208 Mg m⁻³; F(000) = 560; final R[F² > 2σ(F²)] = 0.049 and wR(F²) = 0.138 for 2529 reflections observed with I > 2σ(I).

With C▬H = 0.95 to 0.98 Å; U_iso(H) = kU_eq(C), k = 1.5 for ▬CH₃ and 1.2 for the other H atoms, all the hydrogen atoms were arranged geometrically and allowed to drive on their parent atoms.

In (Figure 4), with the maximum deviation = 0.004 (1) Å for N3, the imidazole ring is planar. This ring makes dihedral angles of 68.91 (8)°, and 20.43 (9)° with the (C11▬C16) and (C21▬C26) rings, respectively. 73.62 (8)° is the dihedral angle among the (C11▬C16) and (C21▬C26) rings. The C12▬H12⋯N3ⁱ and C16▬H16⋯N3ⁱⁱ intermolecular nonclassical hydrogen bonds stabilize the packing (Figure 5). Symmetry codes are: (i) −x + 2, −y + 1, −z and (ii) −x + 2, −y + 2, −z.

Figure 4.

The thermal displacement ellipsoid plot [20] is shown at a 30% probability level.

Figure 5.

The crystal packing with hydrogen bonds [21], viewed along the a-axis.

The ORTEP-3 for Windows drew the thermal displacement ellipsoid plot with a 30% probability level [20] (Figure 4). The crystal packing using the PLATON [21] was viewed along the a-axis (Figure 5).

3.3 Structural analysis of 2-(4-fluorophenyl)-4,5-dimethyl-1-(4-methylphenyl)-1H-imidazole (FPDMMPI)

The FPDMMPI’s detailed structure is illustrated in this section [12]. The structure was solved by SHELXS97 [19]. The final crystal structure model is enhanced using the tool SHELXL97 [19].

This compound belongs to the monoclinic crystal system with the space group P2₁/n. Molecular formula: C₁₈H₁₇N₂; molecular weight: 280.34; crystal data: a = 9.8888 (2) Å; b = 7.6693 (1) Å; c = 20.1017 (5) Å; β = 95.915 (1)°; V = 1516.40 (4) ų; Z = 4; D_x = 1.228 Mg m⁻³; F(000) = 592; final R[F² > 2σ(F²)] = 0.049 and wR(F²) = 0.153 for 2617 reflections observed with I > 2σ(I).

With C▬H = 0.93–0.96 Å; U_iso(H) = kU_eq(C), where k = 1.5 for ▬CH₃ and 1.2 for the other H atoms, all the hydrogen atoms were geometrically arranged and admitted to riding on their parent atoms.

In this molecule (Figure 6), the dihedral angles made by (C11▬C16) and (C21▬C26) rings are 72.33 (8)° and 18.71 (8)° with the planar imidazole ring. Benzene rings makes a 75.05 (7)° dihedral angle. The C12▬H12⋯N3 (2 − x, 1 − y, −z) and C16▬H16⋯N3 (2 − x, 2 − y, −z) intermolecular hydrogen bonds stabilize the crystal (Figure 7).

Figure 6.

The thermal displacement ellipsoid plot [20] is shown at a 30% probability level.

Figure 7.

The crystal packing with hydrogen bonds [21], viewed along the a-axis.

The ORTEP-3 for Windows drew the thermal displacement ellipsoid plot with a 30% probability level [20] (Figure 6). The crystal packing using the PLATON [21] was viewed along the a-axis (Figure 7).

3.4 Structural analysis of 1-(3,5-dimethylphenyl)-4,5-dimethyl-2-phenyl-1H-imidazole hemihydrate (DMPDMPIHH)

The specifics of DMPDMPIHH’s structure are shown in this section [13]. The crystal structure was solved by SHELXS97 [19]. The final crystal structure model is enhanced using the tool SHELXL97 [19].

This compound belongs to the orthorhombic crystal system with the space group Pbcn. Molecular formula: C₁₉H₂₀N₂.0.5H₂O; molecular weight: 285.38; crystal data: a = 16.7611 (2) Å; b = 11.5467 (2) Å; c = 16.6563 (2) Å; α = β = γ = 90°; V = 3223.58 (8) ų; Z = 8; D_X = 1.176 Mg m⁻³; F(000) = 1224; final R[F² > 2σ(F²)] = 0.062 and wR(F²) = 0.171 for 2630 reflections observed with I > 2σ(I).

The atom H1W was introduced alongside the atom O1W, found in a differential Fourier map and refined without restriction. O1W is home to an additional hydrogen atom that follows the (−x, y, 1/2 − z) symmetry. With C▬H = 0.95–0.98 Å; U_iso(H) = kU_eq(C), where k = 1.5 for ▬CH₃ and 1.2 for the other H atoms, the residual H atoms were oriented geometrically and acknowledged riding on their parent atoms.

In this compound (Figure 8), with a maximum deviation of 0.005 (1) Å for N3, the imidazole ring is planar. The imidazole ring makes dihedral angles of 67.46 (10) and 23.10 (11)° with the (C11▬C16) and (C21▬C26), respectively. 68.22 (10)° is the dihedral angle between the benzene and phenyl rings. Intermolecular O1W▬H1W⋯N3 (−x, y, −z + 1/2) and C12▬H12⋯N3 (−x, −y + 1, −z) hydrogen bonds are found in the crystal structure (Figure 9).

Figure 8.

The thermal displacement ellipsoid plot [20] is shown at a 30% probability level.

Figure 9.

The crystal packing with hydrogen bonds [21] is viewed along the b-axis.

The ORTEP-3 for Windows drew the thermal displacement ellipsoid plot with a 30% probability level [20] (Figure 8). The crystal packing using the PLATON [21] was viewed along the b-axis (Figure 9).

3.5 Structural analysis of 1-(3,5-dimethylphenyl)-2-(4-fluorophenyl)-4,5-dimethyl-1H-imidazole (DMPFPDMI)

This section depicts the structure details of DMPFPDMI [14]. SHELXS97 [19] solved the crystal structure. The program SHELXL97 [19] refines the final crystal structure model.

This compound belongs to the triclinic crystal system with the space group Pī. Molecular formula: C₁₉H₁₉FN₂; molecular weight: 294.36; crystal data: a = 8.4226 (10) Å; b = 9.5572 (10) Å; c = 11.0351 (11) Å; α = 105.423 (9)°; β = 105.677 (9)°; γ = 95.781 (9)°; V = 810.07 (17) ų; Z = 2; D_x = 1.207 Mg m⁻³; F(000) = 312; final R[F² > 2σ(F²)] = 0.052 & wR(F²) = 0.159 for 2771 reflections observed with I > 2σ(I).

All of the H atoms admitted to riding on their parent atoms and were directed geometrically, with C▬H = 0.95–0.98 Å; U_iso(H) = kU_eq(C), where k = 1.5 for ▬CH₃ and 1.2 for the other H atoms.

In this compound (Figure 10), with a maximum deviation of 0.0015 (9) Å for C4, the imidazole ring is planar. The imidazole ring makes dihedral angles of 77.61 (9) and 26.93 (10)° with the (C11▬C16) and (C21▬C26) rings, respectively. 78.84 (8)° is the dihedral angle among the (C11▬C16) and (C21▬C26) rings. A C12—H12···π (−x, −y, −z + 1) interaction involving the (C21▬C26) ring stabilizes the crystal.

Figure 10.

The thermal displacement ellipsoid plot [20] is shown at a 30% probability level.

The ORTEP-3 for Windows drew the thermal displacement ellipsoid plot with a 30% probability level [20] (Figure 10).

3.6 Structural analysis of 2-(4-fluorophenyl)-1-(4-methoxyphenyl)-4,5-dimethyl-1H-imidazole (FPMOPDMI)

This section depicts the structure details of FPMOPDMI [15]. SHELXS97 [19] solved the crystal structure. The program SHELXL97 [19] refines the final crystal structure model.

This compound belongs to the monoclinic crystal system with the space group P2₁/c. Molecular formula: C₁₈H₁₇FN₂O; molecular weight: 296.34; crystal data: a = 8.5132 (1) Å; b = 9.5128 (2) Å; c = 19.2610 (3) Å and β = 96.798 (2)°; V = 1548.87 (4) ų; Z = 4; D_x = 1.271 Mg m⁻³; F(000) = 624; final R[F² > 2σ(F²)] = 0.041 and wR(F²) = 0.130 for 2744 reflections observed with I > 2σ(I).

With C▬H = 0.93 Å for Csp² and 0.96 Å for Csp³, and U_iso(H) = kU_eq(C), where k = 1.5 for ▬CH₃ and 1.2 for the other H atoms, all the hydrogen atoms were guided geometrically and admitted to riding on their parent atoms.

In this molecule (Figure 11), with a maximum deviation of 0.005 (1) Å for C2, the imidazole ring is planar. The imidazole ring makes dihedral angles of 76.46 (7)° and 40.68 (7)° with the (C11▬C16) and (C21▬C26) rings, respectively. 71.25 (6)° is the dihedral angle among benzene rings. No classical hydrogen bonds are found in the crystal.

Figure 11.

The thermal displacement ellipsoid plot [20] is shown at a 30% probability level.

The ORTEP-3 for Windows drew the thermal displacement ellipsoid plot with a 30% probability level (Figure 11) [20].

3.7 Structural analysis of 1-(3,5-dimethoxyphenyl)-2-(4-fluorophenyl)-4,5-dimethyl-1H-imidazole (DMOPFPDMI)

This section depicts the structure details of DMOPFPDMI [16]. SHELXS97 [19] solved the crystal structure. The program SHELXL97 [19] refines the final crystal structure model.

This compound belongs to the monoclinic crystal system with the space group P2₁/n. Molecular formula: C₁₉H₁₉FN₂O₂; molecular weight: 326.36; crystal data: a = 6.9654 (1) Å; b = 17.8520 (3) Å; c = 13.7121 (3) Å; β = 97.833 (2)°; V = 1689.14 (5) ų; Z = 4; D_x = 1.283 Mg m⁻³; F(000) = 688; final R[F² > 2σ(F²)] = 0.046 and wR(F²) = 0.138 for 2723 reflections observed with I > 2σ(I).

The H atoms were all geometrically directed, with C▬H = 0.93–0.96 Å; U_iso(H) = kU_eq(C), where k = 1.5 for ▬CH₃ and 1.2 for the remaining H atoms. All of the H atoms are acknowledged to ride on their parent atoms.

In this compound, in Figure 12, with a maximum deviation of 0.0030 (8) Å for C4, the imidazole ring is planar. The imidazole ring makes dihedral angles of 66.45 (7) and 29.98 (7)° with the (C11▬C16) and (C21▬C26) rings, respectively. The dihedral angle among the benzene rings is 64.79 (7)°. A C23▬H23⋯π (x − 1/2, −y + 1/2, z − 1/2) interaction involving the imidazole (N1/C2/N3/C4/C5) ring is found in the crystal structure. The ▬O▬CH₃ groups were disordered [occupancy factors: 0.803 (4) & 0.197 (4)]. The F atom is disordered [occupancy factors: 0.929 (4) & 0.071 (4)].

Figure 12.

The thermal displacement ellipsoid plot [20] is shown at a 30% probability level. The minor component of ▬O▬CH₃ and F atoms was omitted for clarity.

The ORTEP-3 for Windows drew the thermal displacement ellipsoid plot with a 30% probability level (Figure 12) [20].

3.8 Structural analysis of 2-(4-fluorophenyl)-1,4,5-triphenyl-1H-imidazole (FPTPI)

This section depicts the structure details of FPTPI [17]. SHELXS86 [19] solved the crystal structure. The program SHELXL97 [19] refines the final crystal structure model.

This compound belongs to the triclinic crystal system with the space group Pī. Molecular formula: C₂₇H₁₉FN₂; molecular weight: 390.44; crystal data: a = 10.1794 (5) Å; b = 10.5239 (6) Å; c = 10.6175 (6) Å; α = 80.750 (5)°; β = 85.776 (4)°; γ = 67.348 (5)°; V = 1035.95 (11) ų; Z = 2; D_x = 1.252 Mg m⁻³; F(000) = 408; final R[F² > 2σ(F²)] = 0.049 and wR(F²) = 0.128 for 3489 reflections observed with I > 2σ(I).

All the H atoms were directed geometrically and admitted to riding on their parent atoms with C▬H = 0.93 Å and U_iso(H) = 1.2U_eq (parent atom).

In Figure 13, the imidazole ring is planar with a maximum deviation = 0.004 (1) Å for N1. The dihedral angles made by the imidazole ring with the (C11▬C16), (C21▬C26), (C41▬C46), and (C51▬C56) rings are 62.80 (6), 36.98 (6), 33.16 (6) and 46.24 (6)°, respectively. The dihedral angles made by the (C11▬C16) ring are 54.26 (6), 85.21 (7), and 65.02 (6) ° with the fluorophenyl, (C41▬C46) and (C51▬C56) rings attached to C4 and C5, respectively. The (C41▬C46) ring makes the dihedral angle of 51.10 (6)° with the (C51▬C56) ring. The crystal exhibits no conventional hydrogen bond interactions.

Figure 13.

The thermal displacement ellipsoid plot [20] is shown at a 30% probability level.

The ORTEP-3 for Windows drew the thermal displacement ellipsoid plot with a 30% probability level [20] (Figure 13).

4. Comparative structural study of the eight imidazole derivatives

Section 3 presented the single crystal X-ray structure analyses of eight closely related organic imidazole compounds. All the eight structures have the imidazole core essentially as the basic skeleton, with different groups (DMDPIMH: ▬CH₃, ▬CH₃, ▬C₆H₅, ▬C₆H₅, with H₂O, DMPPTI: ▬CH₃, ▬CH₃, ▬C₆H₅, ▬C₆H₄▬CH₃, FPDMMPI: ▬CH₃, ▬CH₃, ▬C₆H₄▬F, ▬C₆H₄▬CH₃, DMPDMPIHH: ▬CH₃, ▬CH₃, ▬C₆H₅, ▬C₆H₃▬2(CH₃), with 0.5H₂O, DMPFPDMI: ▬CH₃, ▬CH₃, ▬C₆H₄▬F, ▬C₆H₃▬2(CH₃), FPMOPDMI: ▬CH₃, ▬CH₃, ▬C₆H₄▬F, ▬C₆H₄▬O▬CH₃, DMOPFPDMI: ▬CH₃, ▬CH₃, ▬C₆H₄▬F, ▬C₆H₃▬2(O▬CH₃), FPTPI: ▬C₆H₅, ▬C₆H₅, ▬C₆H₄▬F, ▬C₆H₅) as different substituents. The structure elucidation of the compounds has revealed a few features, such as (1) the hydrogen bonds: O▬H…N, O▬H…O, C▬H…N; and (2) the interactions C▬H…π.

C▬H…π interactions: Weak acids and soft bases interact. A particular hydrogen bond between two such systems is called a C▬H…π interaction. The interactions between aromatic acceptors and C▬H aliphatic donors and those between aromatic acceptors and C▬H donors are the two most prominent. The non-covalent connections that surround these systems are referred to in chemistry as “π interactions” or “π effects” [9].

Related structures: On September 11, 2022, the terms imidazole and 1H-imidazole on IUCr Journals Crystallography Journals Online (https://journals.iucr.org/) returned 6276 and 290 articles, respectively, matching the searches. The IUCr Journals’ paper reference codes: tk2693 (4,5-dimethyl-1,2-diphenyl-1H-imidazole monohydrate), rk2234 (4,5-dimethyl-2-phenyl-1-(p-tolyl)-1H-imidazole), si2269 (2-(4-fluorophenyl)-4,5-dimethyl-1-(4- methylphenyl)-1H-imidazole), hg2722 (1-(3,5-dimethylphenyl)-4,5-dimethyl-2-phenyl-1H-imidazole hemihydrate), hg5018 (1-(3,5-dimethylphenyl)-2-(4-fluorophenyl)-4,5-dimethyl-1H-imidazole), wn2396 (2-(4-fluorophenyl)-1-(4-methoxyphenyl)-4,5-dimethyl-1H-imidazole), hg5156 (1-(3,5-dimethoxyphenyl)-2-(4-fluorophenyl)-4,5-dimethyl-1H-imidazole), and tk2707 (2-(4-fluorophenyl)-1,4,5-triphenyl-1H-imidazole), affirm that the geometry of the five-membered imidazole cores are very like in all the described structures.

Database survey: The search using the CCDC ConQuest (Version 2022.2.0) in the Cambridge Structural Database (CSD, Version 5.43, update November 2021) [23] for the compound name imidazole gave 21,489 hits, and for the compound name 1H-imidazole gave 9198 hits. A single query on 2D diagram search using the CCDC ConQuest (Version 2022.2.0) gave 142 hits for DMDPIMH (including the CSD Refcode: SUYRUA), 45 hits for DMPPTI (including the CSD Refcode: VABBUX), 5 hits for FPDMMPI (including the CSD Refcode: QUZLED), 25 hits for DMPDMPIHH (including the CSD Refcode: VUZSOZ), one hit for DMPFPDMI (with the CSD Refcode: URALEF), two hits for FPMOPDMI (including the CSD Refcode: YUQBUI), three hits for DMOPFPDMI (including the CSD Refcode: GAPGEL), and six hits for FPTPI (including the CSD Refcode: KUZFUH).

5. Conclusions

The synthesis and single-crystal X-ray structure characterization of new, carefully chosen imidazole derivatives of biological, pharmacological, and technological relevance are covered in the preceding sections. The geometry of these eight imidazole derivatives (bond lengths, bond angles, torsion angles, and dihedral angles between the least-squares planes) shows that the imidazole is essentially planar in the compounds DMDPIMH, DMPPTI, FPDMMPI, DMPDMPIHH, DMPFPDMI, FPMOPDMI, DMOPFPDMI, and FPTPI as expected and as shown by the most recent literature survey ((https://journals.iucr.org/) (CSD, Version 5.43, update November 2021). The imidazole skeleton has a planer five-membered heterocyclic ring, according to the current X-ray analysis. The fundamental geometrical measurements of the imidazole core in the DMDPIMH molecule agree with those found in other closely related imidazole derivatives. Around the imidazole rings, all of the substituent groups are at their predicted locations. The molecular structure and atom connectivity of the aforementioned compounds, as seen in Figures 2,4,6,8,10−13, are confirmed by the X-ray investigation. Finally, the stabilization of the crystal structures is accomplished by the O-H…N, O▬H…O, C▬H…N, and C▬H…π contacts.

Acknowledgments

Aravazhi Amalan Thiruvalluvar acknowledges Professor R. J. Butcher and the late Professor J. P. Jasinski for their help collecting the single-crystal X-ray diffraction data and Professor J. Jayabharathi for her help in synthesizing the compounds.

Conflict of interest

There is no conflict of interest in writing this chapter.

Thanks

Aravazhi Amalan Thiruvalluvar thanks his wife Lilly for all her emotional support and help at various stages of this review writing, his son Uthaya Raj, his daughter-in-law Amudha, and his daughter Manju Princy for their loving support.

A partial crystallographic information file (CIF) for the compound DMDPIMH (only as an example)

data_I

_chemical_name_systematic

;

4,5-Dimethyl-1,2-diphenyl-1<i>H</i>-imidazole monohydrate

;

_chemical_name_common 1H-imidazole

_chemical_formula_moiety 'C17 H16 N2, H2 O'

_chemical_formula_sum 'C17 H18 N2 O'

_chemical_formula_structural 'C17 H16 N2, H2 O'

_chemical_formula_iupac 'C17 H16 N2, H2 O'

_chemical_formula_weight 266.33

_chemical_melting_point 375

_symmetry_cell_setting tetragonal

_symmetry_space_group_name_H-M 'I 41/a'

_symmetry_space_group_name_Hall '-I 4ad'

_cell_length_a 25.5498(2)

_cell_length_b 25.5498(2)

_cell_length_c 9.37920(10)

_cell_angle_alpha 90

_cell_angle_beta 90

_cell_angle_gamma 90

_cell_volume 6122.67(9)

_cell_formula_units_Z 16

_cell_measurement_reflns_used 4027

_cell_measurement_theta_min 4.8917

_cell_measurement_theta_max 77.3788

_cell_measurement_temperature 295(2)

_cell_special_details ?

_exptl_crystal_description 'irregular plate'

_exptl_crystal_colour 'colourless'

_exptl_crystal_size_max 0.53

_exptl_crystal_size_mid 0.42

_exptl_crystal_size_min 0.18

_exptl_crystal_size_rad ?

_exptl_crystal_density_diffrn 1.156

_exptl_crystal_density_meas ?

_exptl_crystal_density_method 'Not Measured'

_exptl_crystal_F_000 2272

_exptl_absorpt_coefficient_mu 0.572

_exptl_absorpt_correction_type multi-scan

_exptl_absorpt_process_details

;

(CrysAlis Pro; Oxford Diffraction, 2010)

;

_exptl_absorpt_correction_T_min 0.80515

_exptl_absorpt_correction_T_max 1.00000

_diffrn_ambient_temperature 295(2)

_diffrn_radiation_type 'CuK\a'

_diffrn_radiation_wavelength 1.54184

_diffrn_radiation_source 'Enhance (Cu) X-ray Source'

_diffrn_radiation_monochromator graphite

_diffrn_measurement_device_type 'Oxford Diffraction Xcalibur Ruby Gemini'

_diffrn_measurement_method '\w scans'

_diffrn_detector_area_resol_mean 10.5081

_diffrn_reflns_number 8078

_diffrn_reflns_av_R_equivalents 0.0190

_diffrn_reflns_av_sigmaI/netI 0.0162

_diffrn_reflns_theta_min 4.90

_diffrn_reflns_theta_max 77.60

_diffrn_reflns_theta_full 67.50

_diffrn_measured_fraction_theta_max 0.953

_diffrn_measured_fraction_theta_full 0.971