Crystal structure of 1-(2,6-diisopropylphenyl)-1H-imidazole

At 106 (2) K, the title molecule has monoclinic P21/c symmetry with four molecules in the unit cell. The imidazole ring is rotated 80.7 (1)° relative to the phenyl ring. Intermolecular stabilization primarily results from close contacts between the N-atom at the 3-position on the imidazole ring and the C—H bond at the 4-position on the neighboring DippIm.


Chemical context
Imidazoles are stable aromatic heterocyclic compounds comprised of a five-membered heterocycle containing two non-adjacent nitrogen atoms and three carbon atoms.They are precursors in many synthetic processes and find use in pharmaceuticals and agrochemicals to create antifungal agents and fungicides (Ebel et al., 2000).1-(2,6-Diisopropylphenyl)-1H-imidazole ( Dipp Im) additionally has an aryl ring attached to the imidazole.
Several synthetic approaches towards the synthesis of Dipp Im are reported, with the most common current route being through the one-pot synthesis with glyoxal, formaldehyde, ammonium chloride, and 2,6-diisopropyl aniline, followed by an acidic workup with H 3 PO 4 (Liu et al., 2003).A disadvantage of this general route is that the yields are often low, especially for more hindered imidazoles.An alternative approach followed an Ullmann-type coupling using 2-iodo-1,3-diisopropylbenzene and imidazole, with 10% CuI, 40% N, N 0 -dimethylethylenediamine, and Cs 2 CO 3 , but only resulted in 19% yield of Dipp Im (Alcalde et al., 2005).The highest yield approach with 78% yield was originally reported in 1889 and is from the reaction of 2,6-diisopropyl aniline with thiophosgene (Cl 2 CS) in H 2 O, followed by addition of H 2 NCH 2 CH(OEt 2 ), and acidic workup with HCl and HNO 3 (Wohl & Marckwald, 1889;Johnson et al., 1969).Despite being the first reported method, this synthetic approach is significantly concerning from a chemical safety perspective because thiophosgene is highly toxic.
Dipp Im is often used as a precursor to a variety of Nheterocyclic carbene (NHC) ligands, which are a common ligand class for organometallic chemistry and catalysis (Arduengo, 1999;Hopkinson et al., 2014;Lumiss et al., 2015).To create monodentate NHC ligands, an imidazole is typically reacted with an alkyl or aryl halide to form an imidazolium salt.For bidentate NHC ligands, two imidazoles can be reacted with an alkyl or aryl dihalide to form a bis(imidazolium) salt (Gardiner et al., 1999;Thompson et al., 2022).These imidazolium salts are then deprotonated by a base such as sodium tert-butoxide (NaOtBu) or potassium bis(trimethylsilyl)amide (KHMDS) to form the free carbene ligands (Brendel et al., 2014;Yamamoto et al., 2018).

Supramolecular features
The unit cell contains four full molecules of 2,6-diisopropylphenyl imidazole (Fig. 2).Each molecule is oriented such that the imidazole groups are at 80.7 (1) � relative to the aryl ring, based on the measured C1-N1-C4-C9 torsion .Distances between aryl rings are 6.692A ˚as measured between neighboring C4-C9 centroids, and 5.912 (2) A ˚as measured between C9-C9 on neighboring molecules.There is no uncertainty in the distance between centroids, since these were placed using Figure 1 View of one molecule of Dipp Im with 50% probability ellipsoids.

Figure 2
View of four molecules of Dipp Im in the unit cell with 50% probability ellipsoids, highlighting intermolecular distances and close contacts.Distances between centroids (red circles) are listed without standard deviations because these positions were calculated.
the Mercury program's centroid algorithm (Macrae et al., 2020).Both of these distances are greater than 5 A ˚, supporting no significant �-stacking stabilization (Janiak, 2000).The closest contact between neighboring molecules is between N2� � �H3 at a distance of 2.47 (2) A ˚.This technically can be considered a hydrogen bond (Table 1) because H3 is bound to C3, which is bound to an electronegative atom, N1.Therefore, the supramolecular structure of Dipp Im is primarily stabilized through hydrogen bonding between neighboring imidazoles.

Database survey
A survey of the Cambridge Structural Database (Groom et al., 2016) on August 30, 2023 yielded no structural results for Dipp Im through both a drawn structure search and a search of the full name 1-(2,6-diisopropylphenyl)-1H-imidazole.A SciFinder search (SciFinder, 2018) resulted in a substance match with code 25364-47-0, however no structural data were reported.

Synthesis and crystallization
The synthesis for Dipp Im (Fig. 3) was adapted from a literature procedure (Liu et al., 2003).A 500 mL three-necked roundbottomed flask was charged with 10.01 g (0.0564 mol, 1 eq.) of 2,6-diisopropylaniline followed by 8.20 g (0.141 mol, 1 eq.) of 40% aqueous glyoxal and approximately 100 mL of methanol.The resulting color changed from a clear yellow to a rusty orange solution with a yellow precipitate.Using a funnel, 6.03 g (0.112 mol, 2 eq.) of ammonium chloride and 9.16 g (0.305 mol, 2 eq.) of 37% aqueous formaldehyde were added to the round-bottomed flask and diluted with 130 mL of methanol.The mixture was refluxed for 1 h at 368 K, resulting in a dark-brown solution.The flask was removed from the heat and cooled to room temperature before being placed in an ice bath to cool, followed by addition of 15 mL (0.15 mol, 2 eq.) of phosphoric acid over the course of 12 minutes.After addition, it was refluxed at 368 K for 14.5 h, resulting in an opaque darkred solution.The solution was cooled to room temperature and concentrated in vacuo.The dark-brown residue was poured over 300 g of ice and neutralized with a concentrated potassium hydroxide solution until the pH reached 9, resulting in a light-brown solution with a dark-brown precipitate.The mixture was extracted three times with approximately 100 mL of diethyl ether, washed 3 times with approximately 100 mL of water, and washed three times with approximately 100 mL of brine.The mixture was transferred to a 1 L round-bottom flask, dried with sodium sulfate, and left to dry for approximately 20 h, resulting in a dark-brown solution.The sodium sulfate was removed by gravity filtration and the solution was concentrated in vacuo resulting in a light-brown solid.The solid was then recrystallized with ethyl acetate, resulting in 1.33 g (10.4% yield) of colorless crystals.The product was characterized with 1 H NMR and the results were consistent with reported literature values (Liu et al., 2003).
Reaction scheme.

Special details
Geometry.All esds (except the esd in the dihedral angle between two l.s.planes) are estimated using the full covariance matrix.The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry.An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s.planes.
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å 2 )

Table 2
Experimental details.