Heteroannulation Reaction of α-Aminoketones for the Efficient Synthesis of 4-Imidazolin-2-ones and 2-Thiones

Abstract

The hydrogenation of α-oximinoketones in methanol/HCl afforded α-aminoketones, which were applied without purification to the synthesis of 4-imidazolin-2-ones and 2-thiones, including chiral derivatives. The latter two series were obtained in high yields by a heteroannulation reaction of α-aminoketones with isocyanates and isothiocyanates, respectively. A double condensation of the α-aminoketones with two mol equivalents of the isocyanates produced a series of 4,5-dialkyl-N,3-diaryl-2-oxo-2,3-dihydro-1H-imidazole-1-carboxamides. With isothiocyanates, a single condensation reaction furnished a series of 4,5-dialkyl-1-aryl-1H-imidazole-2(3H)-thiones, which underwent alkylation with alkyl halides to form the corresponding 1-aryl-2-thioalkyl-1H imidazoles in high yields.

Keywords:
α-oximinoketones; α-aminoketones; 4-imidazolin-2-ones; 4-imidazolin-2-thiones; heteroannulation

Introduction

Substituted α-oximinoketones constitute versatile and attractive building blocks for the synthesis of numerous α-aminoketones¹,² and azaheterocycles.³-⁷ In particular, α-aminoketones exhibit strong pharmacological activity⁸-¹⁰ and serve as common precursors of azaheterocyclic compounds.⁶,¹¹ 1H-Imidazole N-oxides are an example of azaheterocycles that can be readily constructed in one step by reacting α-oximinoketones with hexahydrotriazines,¹²-¹⁴ revealing their broad synthetic potential.¹⁵-¹⁸ Apart from providing antibacterial and antiparasitic activity,¹⁹ 1H-imidazole N-oxides act as efficient substrates for the preparation of 4-imidazolin-2-ones.²⁰,²¹

4-Imidazolin-2-ones, found in naturally occurring alkaloids,²²,²³ are relevant heterocycles due to their pharmacological activity as antioxidants,²⁴ cytotoxic and antitumor agents,²⁵ D4 dopamine antagonists²⁶ and inhibitors of MurB enzyme.²⁷ Moreover, they can be included in the design of imidazole-containing new drugs.²⁸ Among the many methodologies developed for the synthesis of these versatile heterocycles⁴,²⁹-³¹ are the condensation of carbonyl compounds with substituted ureas²⁶,³² or isocyanates,³³ the intramolecular transposition of N-acyliminium species,³⁴ the transition metal-catalyzed insertion reactions,³⁵ the thermal reaction of α-aminoketones with isocyanates,³⁶ and the Ag(I)-catalyzed cycloisomerization of propargylic ureas.³⁷

Analogous heterocycles are the 4-imidazolin-2 thiones and their 2-alkylthio-1H-imidazole derivatives. They have cytotoxic properties²⁵ and the capacity to inhibit various enzymes, such as 15-lipoxygenase (associated with diverse diseases, including atherosclerosis, cancer and inflammatory disorders),³⁸ cyclooxygenase, acyltransferase, and p38 MAP kinase.¹¹,³⁹-⁴¹ Hence, there have also been intense efforts to design new and more efficient synthetic routes for the preparation of 4-imidazolin-2-thiones.¹²,¹³ Among the possibilities thus far discovered are the reaction of benzoins, α-diketones, α-aminoketones or α-oximinoketones in the presence of ammonium thiocyanate,⁴²-⁴⁴ isothioisocyanates⁴⁵ or thiourea.⁴⁶ The synthesis of their 2-alkylthio-1H imidazole derivatives has been easily achieved by alkylation of the corresponding 4-imidazolin-2-thione precursor,¹¹,³⁹,⁴⁰ or by treatment of 1H-imidazole N-oxide derivatives with 2,2,4,4-tetramethylcyclobutane-1,3-dithiane.¹²,⁴⁷

Our group recently reported the development of new 1H-imidazole N-oxide derivatives 3 via the reaction of functionalized α-oximinoketones 1 with chiral hexahydrotriazines 2, and their conversion into imidazoline-based potential chiral auxiliaries 4 through a short and highly diastereoselective procedure.²¹ As part of the ongoing effort to expand the scope of the synthetic applications of α-oximinoketones 1, the aim of the current study was to transform these compounds into α-aminoketones 5, to be used for the synthesis of a series of 4,5-disubstituted N,3 diaryl-2-oxo-2,3-dihydro-1H imidazol-1-carboxamides 6 or 4,5-disubstituted 1-aryl-1H-imidazol-2(3H)-thiones 7 (Scheme 1).

Scheme 1
Synthesis of imidazolidine- and imidazoline-based derivatives 4, 6 and 7.

Results and Discussion

Synthesis of α-oximinoketones 1a-1d was carried out by a previously described methodology (Scheme 2).²¹ Briefly, α-oximinoketones 1a-1b were prepared by treating the symmetrical α-diketones 8a-8b with hydroxylamine hydrochloride. The reaction of the latter reagent with the unsymmetrical dione 8c generated an inseparable mixture of two α-oximinoketones 1c/1d (8:2). As a successful alternative, direct nitrosation conditions¹,⁴⁸ of 2-pentanone (8d) and 3-pentanone (8e) afforded α-oximinoketones 1c and 1d, respectively, in good yield (Scheme 2).

Scheme 2
Synthesis of α-oximinoketones 1a-1d, α-aminoketones 5a-5d and 4-imidazolin-2-ones 10-13 (for R³, see Table 1).

Through Pd(0)-catalyzed hydrogenolysis in the presence of hydrochloric acid,³³ α-oximinoketones 1a-1d were converted into α-aminoketones 5a-5d, their corresponding chlorhydrates (Scheme 2), in almost quantitative yields, as shown by the ¹H nuclear magnetic resonance (NMR) spectra of the crude mixtures. The isolation of the respective hydrochloride salts was necessary to avoid the dimerization of the free α-aminoketone.⁴⁹,⁵⁰

Without purification, α-aminoketones 5a-5d were thermally reacted with isocyanates 9a-9i to furnish the series of 2-oxo-2,3-dihydro-1H-imidazole-1-carboxamides 10-13 in moderate to good yields (Scheme 2, Table 1). Unexpectedly, the formation of imidazol-2-one 14 was not observed,³⁶ even when using a sub-equimolar amount of 9 (Scheme 3). Compound 14 was probably an intermediate in the formation of 10-13 via an N-addition of the unsubstituted nitrogen atom to another molecule of isocyanate. Considering that 14 was not detected in the crude reaction mixtures, the last step of the process is likely faster than the first step, which is the addition of the α-aminoketones 5a-5d to arylisocyanates 9a-9i to afford the carbamate intermediate I and the subsequent cyclization step to give hemiaminal II. However, it is also possible that the competitive intermolecular addition to 9 occurred from the internal urea moiety of I to generate intermediate III, followed by cyclization to provide 10-13.³⁶

Scheme 3
Plausible reaction mechanisms for the formation of 2-oxo-2,3-dihydro-1H-imidazole-1-carboxamides 10-13.

Table 1
Preparation of the series of 1H-imidazole-1-carboxamides 10-13 from the reaction of α-aminoketones 5a-5d with isocyanates 9a-9i^a

entry	5	9	R1	R2	R3	Product	Yieldb / %
1	5a	9b	Me	Me	C6H4-3-Cl	10a	82
2	5a	9d	Me	Me	C6H4-4-Me	10b	80
3	5a	9g	Me	Me	C2H4-Cl	10c	87
4	5b	9a	Et	Et	C6H5	11a	85
5	5b	9b	Et	Et	C6H4-3-Cl	11b	90
6	5b	9c	Et	Et	C6H4-3-OMe	11c	88
7	5b	9d	Et	Et	C6H4-4-Me	11d	87
8	5b	9f	Et	Et	n-C3H7	11e	90
9	5b	9h	Et	Et	CH2CH=CH2	11f	88
10	5b	9i	Et	Et	(S)-CH(Me)Ph	11g	89
11	5c	9a	Me	Et	C6H5	12a	62
12	5c	9d	Me	Et	C6H4-4-Me	12b	69
13	5c	9e	Me	Et	C6H4-4-OMe	12c	72
14	5c	9f	Me	Et	n-C3H7	12d	57
15	5c	9h	Me	Et	CH2CH=CH2	12e	54
16	5d	9i	Et	Me	(S)-CH(Me)Ph	13	87

• ^a
  Under N₂ atmosphere, with a-aminoketones 5a-5d (1.0 mol equiv) and isocyanates 9a-9i (2.5 mol equiv) in anhydrous toluene, at 100 °C for 24 h.
• ^b
  Yields were determined after column chromatography.

There was no significant difference in efficiency between the products derived from alkyl or aryl isocyanates. Interestingly, the optically active 1H-imidazol-1 carboxamides 11g and 13 were also prepared in good yields. Actually, the relatively modest yields observed for the derivatives from α-aminoketone 5c were probably due to a lower conversion during the hydrogenolysis of the α-oximinoketone 1c or a higher decomposition of the product 5c, judging by the byproducts observed in the reaction crude mixtures by thin layer chromatography (TLC) analysis.

The structure of novel 2-oxo-2,3-dihydro-1H imidazole-1-carboxamides 10-13 was determined by NMR spectroscopy (supported by 2D experiments, heteronuclear multiple quantum coherence (HMQC) and heteronuclear multiple bond coherence (HMBC)), high-resolution mass spectrometry (HRMS), elemental analysis and X-ray crystallography. The single crystal structure of 12c (Figure 1; for simplicity, only one of the two conformers contained in the asymmetric unit cell is shown, see “X-ray crystallographic structures of 12c and 16a” sub-section, Supplementary Information section) displays a relatively rigid conformation of the N-carboxamide moiety, which is due to the formation of an N-H···O (1.941 Å) hydrogen bond between the exocyclic urea proton atom and the oxygen atom of the imidazol-2-one carbonyl group. Hence, the carboxamide carbonyl group is oriented toward the C-5 alkyl group and has a quasi-coplanar conformation (dihedral angle C5-N1-C1’-O2 = 2.6º) with respect to the plane of the heterocycle. This is probably the reason why the protons of the C-5 alkyl substituent undergo a deshielding effect and their signal is shifted downfield in comparison with the protons of the C-4 alkyl group. However, a shielding effect of the N-3 aryl ring on the latter alkyl group cannot be discarded.⁵¹

Figure 1
Structure of 12c as determined by single-crystal X-ray diffraction (ellipsoids at the 30% probability level).

The plausible formation of 4-imidazolin-2-ones 14 and their attack on the isocyanates 9 to afford the respective 2-oxo-2,3-dihydro-1H-imidazole-1-carboxamides 10-13 is a large part due to the high reactivity of the isocyanates themselves.⁵² This is in contrast to the lower reactivity of isothiocyanates, as was demonstrated in the reaction of α-hydroxyketones.⁵³ Therefore, the reactivity of α-aminoketones 5a-5b with isothiocyanates 15a-15c was evaluated under reaction conditions similar to those used for isocyanates 9 (Table 2). Indeed, 4-imidazolin-2-thiones 16-17 were obtained as the main products in good yields.

Table 2
Preparation of the series of 4-imidazolin-2-thiones 16-17 by the reaction of α-aminoketones 5a-5b with isothiocyanates 15a-15c^a

entry	5	15	R1	R2	R3	Product	Yieldb / %
1	5a	15a	Me	Me	C6H4-3-Cl	16a	64
2	5a	15b	Me	Me	C6H4-3-Me	16b	67
3	5a	15c	Me	Me	C6H4-4-Cl	16c	68
4	5b	15a	Et	Et	C6H4-3-Cl	17a	73
5	5b	15b	Et	Et	C6H4-3-Me	17b	72
6	5b	15c	Et	Et	C6H4-4-Cl	17c	77

• ^a
  Under N₂ atmosphere, with a-aminoketones 5a-5b (1.0 mol equiv) and isothiocyanates 15a-15c (2.5 mol equiv) in anhydrous toluene, at 100 °C for 24 h.
• ^b
  Yields were determined after column chromatography.

The structure of 4-imidazole-2-thiones 16-17 was examined by ¹H and ¹³C NMR spectroscopy, HRMS and elemental analysis. Interestingly, in the ¹H NMR spectra of derivatives 16, the C-5 methyl group is shifted upfield with regard to the C-4 methyl group, which is probably due to the shielding effect of the aryl ring located at the vicinal nitrogen atom. The X-ray crystallography of 16a confirmed its structure (Figure 2), showing that the aryl ring adopts an almost orthogonal conformation in relation to the plane formed by the heterocyclic ring (dihedral angle C5-N1-C1’-C2’ = -117.1º), similar to the descriptions of analogous heterocycles.⁵³-⁵⁷ Unlike other five-membered heterocycles, in which the C-4 and C-5 substituents adopt a nonplanar conformation,⁵⁶ the C-4 and C-5 methyl groups are quasi-eclipsed from each other (dihedral angle C6 C4 C5-C7 = -0.8º), as was observed in the case of its analog, 4,5-dimethyl-4-oxazolin-2-thione 19.⁵³

Figure 2
Structure of 16a as determined by single-crystal X-ray diffraction (ellipsoids at the 30% probability level).

Hence, 4-imidazolin-2-thiones 16-17 were obtained in the absence of the respective carboxamides 18. The presence of the latter compound would have derived from a subsequent attack of heterocycles 16-17 on a second molecule of the isothiocyanates 15a-15c. The results may indicate that a second addition to 15a-15c was impeded by the lower reactivity of the isothiocyanates, as well as the lower nucleophilicity of the N-3 nitrogen atom of 4-imidazole-2-thiones 16-17. The observed behavior can be associated with the size of the sulfur atom and its 3d orbitals,⁵⁸ its high polarizability, as well as the hyperconjugation and inductive effect.⁵⁹,⁶⁰ These factors induce the delocalization of the N-3 nitrogen lone-pair toward the C-2 carbon atom, and thus generate the aromatic character of the heterocycle of 16 and 17. This occurs despite the lower electronegativity of the sulfur (2.58 D) versus nitrogen atom (3.05 D).

Our hypothesis is supported by the X-ray of compound 16a. The distance of the N-3 and C-2 bond (1.343(2) Å) is shorter than that between N-1 and C-2 (1.361(3) Å), indicating a certain double bond character of the former. At the same time, a lengthening of the C2=S double bond should be expected. Indeed, the observed distance of C2=S was in fact longer (1.695(2) Å) than that for a known carbon disubstituted by nitrogen atoms (Y)₂C=S (1.671 Å),⁶¹ but shorter than a single C(sp²)-S bond (1.751 Å).⁶¹

Consequently, the polarization of the electronic density of the N-3 nitrogen lone pair toward the C2=S bond should increase the electronic density at the sulfur atom, stabilizing a formal or incipient negative charge, then increasing its nucleophilicity.⁵⁹,⁶⁰ The latter explains the attack of the sulfur atom on diverse electrophiles (20a-20c) to generate the imidazole-containing products 21a-21c (Scheme 4). Of course, the N-3 nitrogen lone-pair polarization toward the heterocyclic ring reduces its nucleophilic effect, decreasing its reactivity with another molecule of the isothiocyanate and impeding the formation of compound 18.

Scheme 4
Synthesis of 2-(alkylthio)-1-aryl-4,5-diethyl-1H-imidazoles 21a-21c.

Another potential resemblance between 4-imidazolin-2-thiones 17 and 4-oxazolin-2-thiones 19 would be the ability of the sulfur atom to bind to electrophilic species, leading to the formation of aromatic 2-alkylthio-1H imidazole derivatives.³⁹,⁴⁰ If compound 19 undergoes addition to alkyl iodides to provide 2-(thioalkyl)oxazolium iodides,⁵³ compounds 17a-17c will be able to react with electrophiles 20a-20c under basic conditions to furnish the corresponding 2-(alkylthio)-1-aryl-4,5-diethyl-1H imidazoles 21a-21c in high yields (Scheme 4).

The greater capacity of the sulfur atom versus the nitrogen atom (or the enamine-like double bond) to react with electrophiles appears to stem from not only by its nucleophilicity, but also by the polarization of the electron density of the nitrogen atom toward the thiocarbonyl group.¹¹,⁵³ Of course, this effect is also favored by the stability resulting from the formation of a neutral aromatic heterocyclic ring.

Conclusions

The present methodology allows for access to 2-oxo-2,3-dihydro-1H-imidazole-1-carboxamides 10-13 through a heteroannulation reaction between α-aminoketones 5a-5d and isocyanates 9a-9i under thermal conditions, followed by an introduction of a second molecule of the isocyanate. On the other hand, the reaction of α-aminoketones 5a 5b with isothiocyanates 15a-15c, provided the series of 4-imidazole-2-thiones 16-17, in which a second isothiocyanate was not incorporated. Heterocycles 17a-17c underwent an S-alkylation leading to 2-(alkylthio)-1-aryl-4,5-diethyl-1H-imidazoles 21a-21c.

Experimental

General

Melting points were determined on a Krüss KSP 1N capillary melting point apparatus. IR spectra were recorded on a PerkinElmer 2000 spectrophotometer. ¹H and ¹³C NMR spectra were captured on Varian Mercury (300 MHz) and Varian VNMR (500 MHz) instruments, with CDCl₃ as the solvent and tetramethylsilane (TMS) as internal standard. Signal assignments were based on 2D NMR spectra (HMQC and HMBC). Mass spectra (MS) were recorded on Thermo Polaris Q-Trace GC Ultra and Hewlett-Packard 5971A spectrometers. High-resolution mass spectra (HRMS) were obtained (in electron impact mode) on a Jeol JSM-GCMateII spectrometer. Elemental analyses were performed on a CE-440 Exeter Analytical instrument. Analytical thin-layer chromatography was carried out by using E. Merck silica gel 60 F254 coated 0.25 plates, visualized with a long- and short-wavelength UV lamp. Flash column chromatography was conducted over Natland International Co. silica gel (230-400 and 230-400 mesh). All air moisture sensitive reactions were achieved under N₂ using oven-dried glassware. Prior to use, toluene was freshly distilled over sodium, as was CH₂Cl₂ over CaH₂. MeOH were distilled over sodium. K₂CO₃ was dried overnight at 200 °C prior to use. All other reagents (Sigma-Aldrich, St. Louis, MI, USA) were employed without further purification. Compounds 1a-1d were prepared as described.²¹

Syntheses

3-Aminobutan-2-one hydrochloride (5a)

Under H₂ atmosphere (30 psi), a mixture of 1a (0.500 g, 4.95 mmol) and Pd/C (5%) (0.05 g, 0.495 mol) in MeOH/HCl (37%) (9:1, 20 mL) was stirred at 25 ºC for 2 h. The reaction mixture was filtered and the solvent removed under vacuum to give 5a as a reaction crude, which was used in the next step without previous purification.

4-Aminohexan-3-one hydrochloride (5b)

Following the method of preparation for 5a, 1b (0.500 g, 3.88 mmol) and Pd/C (5%) (0.039 g, 0.388 mol) were mixed under H₂ atmosphere to afford 5b as a reaction crude, which was used in the next step without previous purification.

3-Aminopentan-2-one hydrochloride (5c)

Following the method of preparation for 5a, 1c (0.500 g, 4.35 mmol) and Pd/C (5%) (0.044 g, 0.435 mol) were mixed under H₂ atmosphere to furnish 5c as a reaction crude, which was used in the next step without previous purification.

2-Aminopentan-3-one hydrochloride (5d)

Following the method of preparation for 5a, 1d (0.500 g, 4.35 mmol) and Pd/C (5%) (0.044 g, 0.435 mol) were mixed under H₂ atmosphere to provide 5d as a reaction crude, which was used in the next step without previous purification.

N,3-Bis(3-chlorophenyl)-4,5-dimethyl-2-oxo-2,3-dihydro-1H imidazole-1-carboxamide (10a)

In a two-necked round-bottomed flask equipped with a thermometer and condenser, a mixture of 5a (0.123 g, 1.00 mmol) and 9b (0.382 g, 2.49 mmol) in anhydrous toluene (20 mL) was heated at 100 ºC for 24 h. The solvent was removed under vacuum and the residue purified by column chromatography over silica gel (20 g/g crude, hexane/EtOAc, 98:2) to produce 10a (0.31 g, 82%) as a white solid; Rf 0.53 (hexane/EtOAc, 8:2); mp 158 159 °C; IR (KBr) ν / cm^-1 3425, 3044, 2930, 1737, 1698, 1662, 1593, 1553, 1481, 1429, 1387, 1299, 1215, 1075, 781; ¹H NMR (300 MHz, CDCl₃) δ 1.91 (br s, 3H, CH₃-4), 2.45 (br s, 3H, CH₃-5), 7.07 (ddd, J 7.8, 1.8, 1.2 Hz, 1H, H-6’), 7.19-7.25 (m, 2H, Ar-H), 7.27-7.35 (m, 2H, Ar-H), 7.43-7.47 (m, 2H, Ar-H), 7.75 (t, J 2.1 Hz, 1H, H-2’), 11.35 (s, 1H, NH); ¹³C NMR (75.4 MHz, CDCl₃) δ 8.9 (CH₃-4), 11.9 (CH₃-5), 116.0 (C-4), 116.4 (C-5), 118.0 (C-6’), 120.1 (C-2’), 124.1 (C-4’), 125.8 (ArH), 127.9 (ArH), 129.0 (ArH), 129.9 (ArH), 130.5 (ArH), 134.67 (Ar), 134.69 (Ar), 135.1 (Ar), 138.6 (Ar), 148.2 (CONH), 152.4 (C-2); MS (70 eV) m/z, 375 (M⁺-1, 1), 153 (100), 125 (32), 90 (14), 63 (8); anal. calcd. for C₁₈H₁₅Cl₂N₃O₂: C, 57.46; H, 4.02; N, 11.17, found: C, 57.51; H, 4.05; N, 11.14.

4,5-Dimethyl-2-oxo-N,3-di-p-tolyl-2,3-dihydro-1H imidazole-1-carboxamide (10b)

Following the method of preparation for 10a, a mixture of 5a (0.123 g, 1.00 mmol) and 9d (0.33 g, 2.48 mmol) provided 10b (0.268 g, 80%) as a white solid; Rf 0.56 (hexane/EtOAc, 8:2); mp 134-135 °C; IR (KBr) ν / cm^-1 3330, 3027, 2972, 1729, 1692, 1600, 1558, 1516, 1403, 1236, 1111, 820, 747; ¹H NMR (500 MHz, CDCl₃) δ 1.86 (br s, 3H, CH₃-4), 2.30 (s, 3H, CH₃-4’), 2.40 (s, 3H, CH₃-4”), 2.44 (br s, 3H, CH₃-5), 7.11 (d, J 8.5 Hz, 2H, H-3’), 7.16 (d, J 8.5 Hz, 2H, H-2”), 7.29 (d, J 8.5 Hz, 2H, H-3”), 7.43 (d, J 8.5 Hz, 2H, H-2’), 11.30 (s, 1H, NH); ¹³C NMR (125 MHz, CDCl₃) δ 8.8 (CH₃-4), 11.9 (CH₃-5), 20.7 (CH₃-4’), 21.1 (CH₃-4”), 115.3 (C-5), 116.6 (C-4), 120.1 (C-2’), 127.4 (C-2”), 129.4 (C-3’), 130.1 (C-3”), 131.1 (C-1”), 133.4 (C-4’), 134.9 (C-1’), 138.6 (C-4”), 149.2 (CONH), 152.6 (C-2); MS (70 eV) m/z, 334 (M⁺-1, 3), 133 (100), 104 (42), 91 (9), 78 (13), 51 (9); anal. calcd. for C₂₀H₂₁N₃O₂: C, 71.62; H, 6.31; N, 12.53, found: C, 71.64; H, 6.35; N, 12.57.

N,3-Bis(2-chloroethyl)-4,5-dimethyl-2-oxo-2,3-dihydro-1H imidazole-1-carboxamide (10c)

Following the method of preparation for 10a, a mixture of 5a (0.100 g, 0.81 mmol) and 9g (0.213 g, 2.00 mmol) furnished 10c (0.197 g, 87%) as a white solid; Rf 0.19 (hexane/EtOAc, 8:2); mp 110-111 °C; IR (KBr) ν / cm^-1 3252, 2934, 1736, 1690, 1656, 1544, 1443, 1399, 1317, 1214, 751, 657; ¹H NMR (500 MHz, CDCl₃) δ 2.04 (br s, 3H, CH₃-4), 2.31 (br s, 3H, CH₃-5), 3.65-3.70 (m, 4H, H-1’, H-1”), 3.73 (t, J 5.0 Hz, 2H, H-2”), 3.91 (t, J 6.3 Hz, 2H, H-2’), 9.37 (br s, 1H, NH); ¹³C NMR (125 MHz, CDCl₃) δ 8.2 (CH₃-4), 11.7 (CH₃-5), 41.3 (C-2”), 41.6 (C-1’), 42.9 (C-2’), 43.2 (C-1”), 114.7 (C-5), 115.8 (C-4), 151.9 (CONH), 152.8 (C-2); MS (70 eV) m/z, 279 (M⁺-1, 4), 217 (5), 181 (8), 84 (100), 70 (13), 51 (73); anal. calcd. for C₁₀H₁₅Cl₂N₃O₂: C, 42.87; H, 5.40; N, 15.00, found: C, 42.83; H, 5.44; N, 14.96.

4,5-Diethyl-2-oxo-N,3-diphenyl-2,3-dihydro-1H-imidazole-1-carboxamide (11a)

Following the method of preparation for 10a, a mixture of 5b (0.15 g, 1.0 mmol) and 9a (0.298 g, 2.50 mmol) gave 11a (0.28 g, 85%) as a white solid; Rf 0.48 (hexane/EtOAc, 8:2); mp 129-131 °C; IR (KBr) ν / cm^-1 3449, 3035, 2972, 1729, 1690, 1596, 1560, 1493, 1401, 1234, 1111, 760, 692; ¹H NMR (300 MHz, CDCl₃) δ 0.87 (t, J 7.5 Hz, 3H, CH₃CH₂-4), 1.29 (t, J 7.2 Hz, 3H, CH₃CH₂-5), 2.36 (q, J 7.5 Hz, 2H, CH₃CH₂-4), 2.93 (q, J 7.2 Hz, 2H, CH₃CH₂-5), 7.09 (tm, J 7.8 Hz, 1H, H-4’), 7.28-7.36 (m, 4H, H-2”, H-3”), 7.42-7.60 (m, 5H, H-2’, H-3’, H-4”), 11.42 (s, 1H, NH); ¹³C NMR (75.4 MHz, CDCl₃) δ 14.0 (CH₃CH₂-4), 15.3 (CH₃CH₂-5), 16.0 (CH₃CH₂-4), 18.7 (CH₃CH₂-5), 120.2 (C-2’), 121.1 (C-5), 122.4 (C-4), 123.9 (C-4’), 127.8 (C-2”), 128.8 (C-4”), 128.9 (C-3’), 129.6 (C-3”), 133.8 (C-1”), 137.5 (C-1’), 148.8 (CONH), 152.9 (C-2); MS (70 eV) m/z, 335 (M⁺, 2), 216 (59), 201 (100), 185 (12), 158 (16), 132 (15), 91 (43), 77 (9); HRMS (EI) m/z, calcd. for C₂₀H₂₁N₃O₂: 335.1634, found: 335.1637; anal. calcd. for C₂₀H₂₁N₃O₂: C, 71.62; H, 6.31; N, 12.53, found: C, 71.65; H, 6.35; N, 12.54.

N,3-Bis(3-clorophenyl)-4,5-diethyl-2-oxo-2,3-dihydro-1H imidazole-1-carboxamide (11b)

Following the method of preparation for 10a, a mixture of 5b (0.15 g, 1.0 mmol) and 9b (0.384 g, 2.50 mmol) resulted in 11b (0.361 g, 90%) as a white solid; Rf 0.53 (hexane/EtOAc, 8:2); mp 129-131 °C; IR (film) ν / cm^-1 3300, 3068, 2973, 2933, 1732, 1692, 1592, 1546, 1482, 1426, 1394, 1226, 777; ¹H NMR (300 MHz, CDCl₃) δ 0.89 (t, J 7.5 Hz, 3H, CH₃CH₂-4), 1.28 (t, J 7.4 Hz, 3H, CH₃CH₂-5), 2.38 (q, J 7.5 Hz, 2H, CH₃CH₂-4), 2.91 (q, J 7.4 Hz, 2H, CH₃CH₂-5), 7.01 (ddd, J 7.8, 1.5, 1.2 Hz, 1H, H-6’), 7.20-7.28 (m, 2H, ArH), 7.32 (ddd, J 8.4, 1.8, 1.2, 1H, ArH), 7.36 (t, J 2.0 Hz, 1H, H-2”), 7.43-7.51 (m, 2H, ArH), 7.76 (t, J 2.0 Hz, 1H, H-2’), 11.43 (s, 1H, NH); ¹³C NMR (75.4 MHz, CDCl₃) δ 14.0 (CH₃CH₂-4), 15.2 (CH₃CH₂-5), 16.0 (CH₃CH₂-4), 18.7 (CH₃CH₂-5), 118.1 (C-6”), 120.2 (C-2’), 121.6 (C-5), 122.2 (C-4), 124.1 (C-6’), 126.0 (ArH), 128.1 (ArH), 129.2 (ArH), 129.9 (ArH), 130.6 (ArH), 134.7 (Ar), 134.9 (Ar), 135.2 (Ar), 138.6 (Ar), 148.4 (CONH), 152.7 (C-2); MS (70 eV) m/z, 403 (M⁺, 10), 373 (16), 328 (16), 252 (11), 223 (10), 186 (16), 153 (100), 125 (21), 84 (51), 74 (25), 51 (33); HRMS (EI) m/z, calcd. for C₂₀H₁₉N₃O₂Cl₂ [M]⁺: 403.0854; found: 403.0837; anal. calcd. for C₂₀H₁₉N₃O₂Cl₂: C, 59.42; H, 4.74; N, 10.39, found: C, 59.43; H, 4.78; N, 10.36.

4,5-Diethyl-N,3-bis(3-methoxyphenyl)-2-oxo-2,3-dihydro-1H-imidazole-1-carboxamide (11c)

Following the method of preparation for 10a, a mixture of 5b (0.15 g, 1.0 mmol) and 9c (0.373 g, 2.50 mmol) led to 11c (0.344 g, 88%) as a white solid; Rf 0.43 (hexane/EtOAc, 8:2); mp 155 156 °C; IR (KBr) ν / cm^-1 3323, 3067, 2967, 1736, 1602, 1561, 1494, 1460, 1393, 1220, 1037, 778, 741, 689; ¹H NMR (300 MHz, CDCl₃) δ 0.89 (t, J 7.5 Hz, 3H, CH₃CH₂-4), 1.28 (t, J 7.3 Hz, 3H, CH₃CH₂-5), 2.37 (q, J 7.5 Hz, 2H, CH₃CH₂-4), 2.91 (q, J 7.3 Hz, 2H, CH₃CH₂-5), 3.78 (s, 3H, CH₃O), 3.83 (s, 3H, CH₃O), 6.65 (ddd, J 8.1, 2.4, 1.2 Hz, 1H, H-4’), 6.86 (t, J 2.4 Hz, 1H, H-2”), 6.91 (ddd, J 8.1, 2.1, 0.9 Hz, 1H, H-6”), 7.00 (ddd, J 8.1, 2.4, 0.9 Hz, 1H, H-4”), 7.13 (ddd, J 8.1, 2.1, 0.9 Hz, 1H, H-6’), 7.17-7.25 (m, 2H, H-2’, H-5’), 7.41 (t, J 8.1 Hz, 1H, H-5”), 11.45 (s, 1H, NH); ¹³C NMR (75.4 MHz, CDCl₃) δ 14.0 (CH₃CH₂-4), 15.2 (CH₃CH₂-5), 15.9 (CH₃CH₂-4), 18.6 (CH₃CH₂-5), 55.2 (CH₃O), 55.4 (CH₃O), 105.5 (C-2’), 109.9 (C-4’), 112.3 (C-6’), 113.5 (C-2”), 114.5 (C-4”), 119.9 (C-6”), 121.1 (C-5), 122.3 (C-4), 129.6 (C-5”), 130.2 (C-5’), 134.8 (C-1”), 138.7 (C-1’), 148.5 (CONH), 152.7 (C-2), 160.0 (C-3’), 160.3 (C-3’’); MS (70 eV) m/z, 396 (M⁺+1, 4), 246 (100), 233 (25), 231 (48), 182 (24), 149 (23); HRMS (EI) m/z, calcd. for C₂₂H₂₅N₃O₄ [M]⁺: 395.1845, found: 395.1838; anal. calcd. for C₂₂H₂₅N₃O₄: C, 66.82; H, 6.37; N, 10.63, found: C, 66.87; H, 6.41; N, 10.60.

4,5-Diethyl-2-oxo-N,3-di-p-tolyl-2,3-dihydro-1H-imidazole-1-carboxamide (11d)

Following the method of preparation for 10a, a mixture of 5b (0.15 g, 1.0 mmol) and 9d (0.333 g, 2.50 mmol) gave 11d (0.316 g, 87%) as a white solid; Rf 0.63 (hexane/EtOAc, 8:2); mp 131-132 °C; IR (KBr) ν / cm^-1 3330, 2972, 2932, 1729, 1692, 1600, 1559, 1516, 1403, 1237, 1112, 821, 748; ¹H NMR (500 MHz, CDCl₃) δ 0.88 (t, J 7.5 Hz, 3H, CH₃CH₂-4), 1.27 (t, J 7.3 Hz, 3H, CH₃CH₂-5), 2.30 (s, 3H, CH₃-4’), 2.34 (q, J 7.5 Hz, 2H, CH₃CH₂-4), 2.41 (s, 3H, CH₃-4”), 2.91 (q, J 7.3 Hz, 2H, CH₃CH₂-5), 7.10 7.35 (m, 2H, H-3’), 7.17-7.21 (m, 2H, H- 2”), 7.28 7.32 (m, 2H, H-3”), 7.41-7.45 (m, 2H, H-2’), 11.34 (s, 1H, NH); ¹³C NMR (125 MHz, CDCl₃) δ 14.0 (CH₃CH₂-4), 15.3 (CH₃CH₂-5), 16.0 (CH₃CH₂-4), 18.7 (CH₃CH₂-5), 20.8 (CH₃-4’), 21.2 (CH₃-4”), 120.2 (C-2’), 121.0 (C-5), 122.5 (C-4), 127.6 (C-2”), 129.5 (C-3’), 130.2 (C-3”), 131.3 (C-1”), 133.5 (C-4’), 135.0 (C-1’), 138.9 (C 4”), 148.9 (CONH), 153.0 (C-2); MS (70 eV) m/z, 362 (M⁺-1, 10), 339 (9), 226 (10), 209 (12), 196 (13), 165 (69), 133 (90), 120 (100), 106 (65), 77 (85), 59 (50), 51 (89); HRMS (EI) m/z, calcd. for C₂₀H₂₅N₃O₂ [M]⁺: 363.1947, found: 363.1950.

4,5-Diethyl-2-oxo-N,3-dipropyl-2,3-dihydro-1H-imidazol-1 carboxamide (11e)

Following the method of preparation for 10a, a mixture of 5b (0.15 g, 1.0 mmol) and 9f (0.213 g, 2.50 mmol) afforded 11e (0.241 g, 90%) as a yellow oil; Rf 0.50 (hexane/EtOAc, 8:2); IR (film) ν / cm^-1 3316, 2967, 2936, 1723, 1690, 1547, 1424, 1377, 1287, 1116, 763; ¹H NMR (300 MHz, CDCl₃) δ 0.95 (t, J 7.2 Hz, 3H, H-3”), 0.97 (t, J 7.2 Hz, 3H, H-3’), 1.12 (t, J 7.5 Hz, 3H, CH₃CH₂-4), 1.16 (t, J 7.2 Hz, 3H, CH₃CH₂-5), 1.54-1.78 (m, 4H, H-2’, H-2”), 2.40 (q, J 7.5 Hz, 2H, CH₃CH₂-4), 2.78 (q, J 7.2 Hz, 2H, CH₃CH₂-5), 3.25-3.34 (m, 2H, H-1’), 3.49-3.57 (m, 2H, H-1”), 9.20 (br s, 1H, NH); ¹³C NMR (75.4 MHz, CDCl₃) δ 11.2 (C-3”), 11.5 (C-3’), 14.9 (CH₃CH₂-4), 15.3 (CH₃CH₂-5), 15.7 (CH₃CH₂-4), 18.5 (CH₃CH₂-5), 22.6 (C-2”), 22.8 (C-2’), 41.4 (C-1’), 42.6 (C-1”), 120.1 (C-5), 121.0 (C-4), 151.8 (CONH), 153.0 (C-2); MS (70 eV) m/z, 266 (M⁺-1, 1), 115 (62), 98 (89), 86 (90), 84 (100), 69 (14), 56 (55); HRMS (EI) m/z, calcd. for C₁₄H₂₅N₃O₂ [M]⁺: 267.1947, found: 267.1946.

N,3-Diallyl-4,5-diethyl-2-oxo-2,3-dihydro-1H-imidazole-1 carboxamide (11f)

Following the method of preparation for 10a, a mixture of 5b (0.15 g, 1.0 mmol) and 9h (0.210 g, 2.50 mmol) produced 11f (0.229 g, 88%) as a yellow oil, Rf 0.44 (hexane/EtOAc, 8:2); IR (film) ν / cm^-1 3428, 2975, 1722, 1687, 1645, 1542, 1432, 1401, 1258, 991, 923, 763; ¹H NMR (500 MHz, CDCl₃) δ 1.11 (t, J 7.5 Hz, 3H, CH₃CH₂-4), 1.17 (t, J 7.2 Hz, 3H, CH₃CH₂-5), 2.39 (q, J 7.5 Hz, 2H, CH₃CH₂-4), 2.80 (q, J 7.2 Hz, 2H, CH₃CH₂-5), 3.95-3.99 (m, 2H, H-1’), 4.23-4.26 (m, 2H, H-1”), 5.08 (d, J 17.5, 1H, H-3”), 5.14 (dd, J 10.0, 1.5 Hz, 1H, H-3’), 5.20 (dd, J 10.0, 1.0 Hz, 1H, H-3”), 5.26 (dd, J 17.5, 1.5 Hz, 1H, H-3’), 5.82-5.95 (m, 2H, H-2’, H-2”), 9.27 (br s, 1H, NH); ¹³C NMR (125 MHz, CDCl₃) δ 14.7 (CH₃CH₂-4), 15.2 (CH₃CH₂-5), 15.6 (CH₃CH₂-4), 18.4 (CH₃CH₂-5), 42.0 (C-1’), 43.0 (C-1”), 115.9 (C-3’), 116.6 (C-3”), 120.3 (C-5), 121.3 (C-4), 132.6 (C-2”), 134.0 (C-2’), 151.4 (CONH), 152.9 (C-2); MS (70 eV) m/z, 261 (M⁺-2, 4), 96 (100), 84 (20), 67 (7), 57 (43); HRMS (EI) m/z, calcd. for C₁₄H₂₁N₃O₂ [M]⁺: 263.1634, found: 263.1629.

4,5-Diethyl-2-oxo-N,3-bis((S)-1-phenylethyl)-2,3-dihydro-1H-imidazole-1-carboxamide (11g)

Following the method of preparation for 10a, a mixture of 5b (0.15 g, 1.0 mmol) and 9i (0.367 g, 2.50 mmol) delivered 11g (0.34 g, 89%) as a white solid; [α]²⁷_D -67.12 (c 0.132, MeOH); Rf 0.61 (hexane/EtOAc, 8:2); IR (film) ν / cm^-1 3201, 3030, 2973, 1720, 1682, 1536, 1450, 1382, 1258, 1217, 1067, 760, 698; ¹H NMR (500 MHz, CDCl₃) δ 0.85 (t, J 7.5 Hz, 3H, CH₃CH₂-4), 1.14 (t, J 7.5 Hz, 3H, CH₃CH₂-5), 1.53 (d, J 7.0 Hz, 3H, CH₃-2’), 1.86 (d, J 7.2 Hz, 3H, CH₃-2”’), 2.28 (q, J 7.5 Hz, 2H, CH₃CH₂-4), 2.68-2.80 (m, 2H, CH₃CH₂-5), 5.08 (q, J 7.0 Hz, 1H, H-1’), 5.37 (q, J 7.2 Hz, 1H, H-1”’), 7.22-7.40 (m, 10H, Ar-H), 9.62 (d, J 7.5 Hz, 1H, NH); ¹³C NMR (125 MHz, CDCl₃) δ 14.4 (CH₃CH₂-4), 15.2 (CH₃CH₂-5), 16.2 (CH₃CH₂-4), 18.2 (CH₃-2”’), 18.5 (CH₃CH₂-5), 22.9 (CH₃-2’), 49.7 (C-1’), 51.1 (C-1”’), 120.8 (C-5), 121.4 (C-4), 126.0 (C-2”), 126.4 (C-2^IV), 127.0 (C-4” or C-4^IV), 127.4 (C-4^IV or C-4”), 128.5 (C-3” or C-3^IV), 128.6 (C-3^IV or C-3”), 140.4 (C-1^IV), 143.8 (C-1”), 150.8 (CONH), 152.9 (C-2); MS (70 eV) m/z, 147 (M⁺-244, 47), 132 (100), 105 (30), 77 (20); HRMS (EI) m/z calcd. for C₂₄H₂₉N₃O₂ [M]⁺: 391.2260, found: 391.2252; anal. calcd. for C₂₄H₂₉N₃O₂: C, 73.63; H, 7.47; N, 10.73, found: C, 73.61; H, 7.42; N, 10.77.

5-Ethyl-4-methyl-2-oxo-N,3-diphenyl-2,3-dihydro-1H imidazole-1-carboxamide (12a)

Following the method of preparation for 10a, a mixture of 5c (0.137 g, 1.00 mmol) and 9a (0.298 g, 2.50 mmol) furnished 12a (0.198 g, 62%) as a white solid; Rf 0.50 (hexane/EtOAc, 8:2); mp 144-145 °C; IR (KBr) ν / cm^-1 3449, 2975, 1738, 1693, 1598, 1562, 1497, 1393, 1215, 1107, 753; ¹H NMR (500 MHz, CDCl₃) δ 1.26 (t, J 7.5 Hz, 3H, CH₃CH₂-5), 1.89 (s, 3H, CH₃-4), 2.92 (q, J 7.5 Hz, 2H, CH₃CH₂-5), 7.08 (t, J 7.5 Hz, 1H, H-4”), 7.29-7.32 (m, 4H, H-2”, H-3”), 7.40-7.42 (m, 1H, H-4’), 7.49 (t, J 7.5 Hz, 2H, H-3’), 7.56 (d, J 7.5 Hz, 2H, H-2’), 11.39 (s, 1H, NH); ¹³C NMR (125 MHz, CDCl₃) δ 8.7 (CH₃-4), 14.7 (CH₃CH₂), 18.8 (CH₃CH₂), 116.4 (C-4), 120.2 (C-2’), 121.4 (C-5), 123.9 (C-4’), 127.5 (C-2”), 128.6 (C-4”), 128.9 (C-3’), 129.4 (C-3”), 133.7 (C-1”), 137.5 (C-1’), 148.7 (CONH), 152.7 (C-2); MS (70 eV) m/z, 320 (M⁺-1, 5), 216 (44), 201 (100), 187 (20), 158 (17), 132 (23), 91 (36), 77 (50); anal. calcd. for C₁₉H₁₉N₃O₂: C, 71.01; H, 5.96; N, 13.08, found: C, 71.08; H, 5.92; N, 13.12.

5-Ethyl-4-methyl-2-oxo-N,3-di-p-tolyl-2,3-dihydro-1H imidazole-1-carboxamide (12b)

Following the method of preparation for 10a, a mixture of 5c (0.137 g, 1.00 mmol) and 9d (0.333 g, 2.50 mmol) provided 12b (0.241 g, 69%) as a white solid; Rf 0.52 (hexane/EtOAc, 8:2); mp 140-141 °C; IR (KBr) ν / cm^-1 3424, 3031, 2929, 1731, 1600, 1559, 1515, 1400, 1320, 1290, 1240, 1107, 822, 749; ¹H NMR (500 MHz, CDCl₃) δ 1.25 (t, J 7.3 Hz, 3H, CH₃CH₂-5), 1.87 (s, 3H, CH₃-4), 2.30 (s, 3H, CH₃-4’), 2.40 (s, 3H, CH₃ 4”), 2.90 (q, J 7.2 Hz, 2H, CH₃CH₂-5), 7.11 (d, J 8.5 Hz, 2H, H-3’), 7.17 (d, J 8.5 Hz, 2H, H- 2”), 7.29 (d, J 8.5 Hz, 2H, H-3”), 7.44 (d, J 8.5 Hz, 2H, H-2’), 11.32 (s, 1H, NH); ¹³C NMR (125 MHz, CDCl₃) δ 8.6 (CH₃-4), 14.7 (CH₃CH₂-5), 18.8 (CH₃CH₂-5), 20.7 (CH₃-4’), 21.1 (CH₃ 4”), 116.4 (C-4), 120.2 (C-2’), 121.2 (C-5), 127.3 (C-2”), 129.4 (C-3’), 130.1 (C-3”), 131.1 (C-1”), 133.4 (C-4’), 135.0 (C-1’), 138.6 (C-4”), 148.8 (CONH), 152.8 (C-2); MS (70 eV) m/z, 349 (M⁺, 3), 133 (100), 104 (44), 84 (18), 51 (13); anal. calcd. for C₂₁H₂₃N₃O₂: C, 72.18; H, 6.63; N, 12.03, found: C, 72.18; H, 6.64; N, 12.02.

5-Ethyl-N,3-bis(4-methoxyphenyl)-4-methyl-2-oxo-2,3 dihydro-1H-imidazole-1-carboxamide (12c)

Following the method of preparation for 10a, a mixture of 5c (0.137 g, 1.00 mmol) and 9e (0.373 g, 2.50 mmol) led to 12c (0.274 g, 72%) as a pale yellow solid; Rf 0.24 (hexane/EtOAc, 8:2); mp 155-156 °C; IR (KBr) ν / cm^-1 3064, 2971, 1722, 1692, 1604, 1560, 1514, 1402, 1246, 1180, 1032, 824, 755; ¹H NMR (500 MHz, CDCl₃) δ 1.25 (t, J 7.3 Hz, 3H, CH₃CH₂-5), 1.87 (s, 3H, CH₃-4), 2.90 (q, J 7.3 Hz, 2H, CH₃CH₂-5), 3.78 (s, 3H, CH₃O-4’), 3.85 (s, 3H, CH₃O-4”), 6.86 (d, J 9.0 Hz, 2H, H-3’), 7.00 (d, J 9.0 Hz, 2H, H-3”), 7.21 (d, J 9.0 Hz, 2H, H-2”), 7.46 (d, J 9.0 Hz, 2H, H-2’), 11.24 (s, 1H, NH); ¹³C NMR (125 MHz, CDCl₃) δ 8.7 (CH₃-4), 14.8 (CH₃CH₂-5), 18.8 (CH₃CH₂-5), 55.4 (CH₃O-4’), 55.5 (CH₃O-4”), 114.1 (C-3’), 114.7 (C-3”), 116.6 (C-4), 121.0 (C-5), 121.9 (C-2’), 126.4 (C-1”), 128.8 (C-2”), 130.7 (C-1’), 149.0 (CONH), 152.9 (C-2), 156.2 (C-4’), 159.6 (C-4”); MS (70 eV) m/z, 382 (M⁺+1, 1), 149 (100), 134 (60), 106 (39), 78 (14); anal. calcd. for C₂₁H₂₃N₃O₄: C, 66.13; H, 6.08; N, 11.02, found: C, 66.16; H, 6.12; N, 11.00.

5-Ethyl-4-methyl-2-oxo-N,3-dipropyl-2,3-dihydro-1H imidazole-1-carboxamide (12d)

Following the method of preparation for 10a, a mixture of 5c (0.137 g, 1.00 mmol) and 9f (0.213 g, 2.50 mmol) generated 12d (0.144 g, 57%) as a pale orange oil; Rf 0.28 (hexane/EtOAc, 8:2); IR (film) ν / cm^-1 3265, 2966, 2934, 1724, 1687, 1655, 1550, 1460, 1398, 1257, 1214, 762; ¹H NMR (500 MHz, CDCl₃) δ 0.94 (t, J 7.0 Hz, 3H, H-3”), 0.97 (t, J 7.0 Hz, 3H, H-3’), 1.14 (t, J 7.3 Hz, 3H, CH₃CH₂-5), 1.57-1.69 (m, 4H, H-2’, H-2”), 2.00 (s, 3H, CH₃-4), 2.78 (q, J 7.3 Hz, 2H, CH₃CH₂-5), 3.27-3.32 (m, 2H, H-1’), 3.54 (t, J 7.0 Hz, 2H, H-1”), 9.17 (br s, 1H, NH); ¹³C NMR (125 MHz, CDCl₃) δ 7.9 (CH₃-4), 11.1 (C-3’), 11.2 (C-3”), 14.9 (CH₃CH₂-5), 18.4 (CH₃CH₂-5), 22.6 (C-2’), 22.7 (C-2”), 41.4 (C-1’), 42.5 (C-1”), 115.1 (C-4), 120.2 (C-5), 151.7 (CONH), 152.9 (C-2); MS (70 eV) m/z, 253 (M⁺, 6), 169 (15), 168 (100), 154 (11), 153 (89), 151 (13), 139 (6), 126 (14), 111 (38); anal. calcd. for C₁₃H₂₃N₃O₂: C, 61.63; H, 9.15; N, 16.59, found: C, 61.67; H, 9.11; N, 16.61.

N,3-Diallyl-5-ethyl-4-methyl-2-oxo-2,3-dihydro-1H imidazole-1-carboxamide (12e)

Following the method of preparation for 10a, a mixture of 5c (0.137 g, 1.00 mmol) and 9h (0.208 g, 2.50 mmol) formed 12e (0.134 g, 54%) as a pale yellow oil; Rf 0.26 (hexane/EtOAc, 8:2); IR (film) ν / cm^-1 3319, 2971, 2935, 1724, 1689, 1542, 1438, 1407, 1260, 1197, 922, 763; ¹H NMR (500 MHz, CDCl₃) δ 1.14 (t, J 7.5 Hz, 3H, CH₃CH₂-5), 1.98 (s, 3H, CH₃-4), 2.80 (q, J 7.5 Hz, 2H, CH₃CH₂-5), 3.94-3.99 (m, 2H, H-1’), 4.22-4.26 (m, 2H, H-1”), 5.08 (dd, J 17.5, 1.0 Hz, 1H, H-3”), 5.14 (dd, J 10.0, 1.5 Hz, 1H, H-3’), 5.19 (dd, J 10.0, 1.0 Hz, 1H, H-3”), 5.27 (dd, J 17.5, 1.5 Hz, 1H, H-3’), 5.80-5.96 (m, 2H, H-2’, H-2”), 9.25 (br s, 1H, NH); ¹³C NMR (125 MHz, CDCl₃) δ 7.8 (CH₃-4), 14.9 (CH₃CH₂-5), 18.4 (CH₃CH₂-5), 42.1 (C 1’), 43.0 (C-1”), 115.5 (C-4), 115.9 (C-3’), 116.7 (C-3”), 120.4 (C-5), 132.5 (C-2”), 134.0 (C-2’), 151.5 (CONH), 152.8 (C-2); MS (70 eV) m/z, 250 (M⁺+1, 30), 249 (M⁺, 9), 167 (18), 166 (100), 152 (20), 151 (54), 125 (19), 82 (9); HRMS (EI) m/z, calcd. for C₁₃H₁₉N₃O₂ [M]⁺: 249.1477, found: 249.1464.

4-Ethyl-5-methyl-2-oxo-N,3-bis((S)-1-phenylethyl]-2,3 dihydro-1H-imidazole-1-carboxamide (13)

Following the method of preparation for 10a, a mixture of 5d (0.137 g, 1.00 mmol) and 9i (0.373 g, 2.50 mmol) gave 13 (0.328 g, 87%) as a pale red oil; [α]²⁹_D -52.27 (c 0.066, MeOH); Rf 0.52 (hexane/EtOAc, 8:2); IR (film) ν / cm^-1 3246, 3030, 2974, 1720, 1685, 1536, 1451, 1377, 1291, 1217, 759, 698; ¹H NMR (300 MHz, CDCl₃) δ 0.81 (t, J 7.5 Hz, 3H, CH₃CH₂-4), 1.53 (d, J 7.2 Hz, 3H, CH₃-2’), 1.86 (d, J 7.2 Hz, 3H, CH₃-2”’), 2.25 (q, J 7.5 Hz, 2H, CH₃CH₂-4), 2.27 (s, 3H, CH₃-5), 5.06 (q, J 6.9 Hz, 1H, H-1’), 5.40 (q, J 7.2 Hz, 1H, H-1”’), 7.20-7.42 (m, 10H, Ar-H), 9.59 (br d, J 7.5 Hz, 1H, NH); ¹³C NMR (75.4 MHz, CDCl₃) δ 11.6 (CH₃-5), 13.8 (CH₃CH₂-4), 16.2 (CH₃CH₂-4), 18.2 (CH₃-2”’), 22.9 (CH₃-2’), 49.7 (C-1’), 50.9 (C-1”’), 114.8 (C-5), 121.4 (C-4), 126.0 (C-2”), 126.3 (C-2^IV), 127.1 (C-4” or C-4^IV), 127.4 (C-4^IV or C-4”), 128.6 (C-3”, C-3^IV), 140.3 (C-1^IV), 143.7 (C-1”), 151.3 (CONH), 152.7 (C-2); MS (70 eV) m/z, 376 (M⁺-H, 2), 147 (45), 132 (100), 105 (30), 77 (20); anal. calcd. for C₂₃H₂₇N₃O₂: C, 73.18; H, 7.21; N, 11.13, found: C, 73.18; H, 7.24; N, 11.18.

1-(3-Chlorophenyl)-4,5-dimethyl-1H-imidazole-2(3H)-thione (16a)

In a two-necked round-bottomed flask provided by a thermometer and condenser, a mixture of 5a (0.123 g, 1.00 mmol) and 15a (0.424 g, 2.50 mmol) in anhydrous toluene (20 mL) was heated at 100 ºC for 24 h. The solvent was removed under vacuum and the residue purified by column chromatography over silica gel (20 g/g crude, hexane/EtOAc, 1:1) to give 16a (0.14 g, 64%) as a yellow solid; Rf 0.56 (hex/AcOEt, 1:1); mp 110-112 °C; IR (film) ν / cm^-1 3086, 2921, 1592, 1494, 1384, 1352, 1243; ¹H NMR (500 MHz, CDCl₃) δ 1.87 (s, 3H, CH₃-5), 2.11 (s, 3H, CH₃-4), 7.24-7.27 (m, 1H, H-6’), 7.33-7.35 (m, 1H, H-4’), 7.43-7.48 (m, 2H, H-2’, H-5’), 11.62 (br s, 1H, NH); ¹³C NMR (125 MHz, CDCl₃) δ 9.1 (CH₃-5), 9.6 (CH₃-4), 120.7 (C-4), 122.1 (C-5), 126.8 (C-6’), 128.7 (C-4’), 129.3 (C-2’), 130.3 (C-5’), 134.9 (C-3’), 137.4 (C-1’), 160.2 (C-2); HRMS (EI) m/z, calcd. for C₁₁H₁₁ClN₂S [M]⁺: 238.0331, found: 238.0329.

4,5-Dimethyl-1-(m-tolyl)-1H-imidazole-2(3H)-thione (16b)

Following the method of preparation for 16a, a mixture of 5a (0.123 g, 1.00 mmol) and 15b (0.373 g, 2.50 mmol) led to 16b (0.146 g, 67%) as a yellow solid; Rf 0.50 (hexane/EtOAc, 1:1); mp 114-116 °C; IR (film) ν / cm^-1 3080, 2921, 1609, 1492, 1385, 1352, 1232, 768, 698; ¹H NMR (500 MHz, CDCl₃) δ 1.84 (s, 3H, CH₃-5), 2.11 (s, 3H, CH₃-4), 2.42 (s, 3H, CH₃-3’), 7.08-7.12 (m, 2H, H-2’, H-6’), 7.26 (br d, J 8.0 Hz, 1H, H-4’), 7.40 (t, J 8.0 Hz 1H, H-5’), 11.44 (br s, 1H, NH); ¹³C NMR (125 MHz, CDCl₃) δ 9.1 (CH₃-4), 9.6 (CH₃-5), 21.3 (CH₃-3’), 120.2 (C-4), 122.4 (C-5), 125.3 (C-6’), 128.8 (C-2’), 129.2 (C-5’), 129.8 (C-4’), 136.3 (C-1’), 139.4 (C-3’), 159.9 (C-2); HRMS (EI) m/z, calcd. for C₁₂H₁₄N₂S [M]⁺: 218.0878, found: 218.0874.

1-(4-Chlorophenyl)-4,5-dimethyl-1H-imidazole-2(3H)-thione (16c)

Following the method of preparation for 16a, a mixture of 5a (0.123 g, 1.00 mmol) and 15c (0.424 g, 2.50 mmol) gave 16c (0.162 g, 68%) as a yellow solid; Rf 0.56 (hexane/EtOAc, 1:1); mp 111-112 °C; IR (film) ν / cm^-1 2922, 1496, 1400, 1350, 1269, 1255, 1089, 749; ¹H NMR (500 MHz, CDCl₃) δ 1.86 (s, 3H, CH₃-5), 2.11 (s, 3H, CH₃-4), 7.26-7.29 (m, 2H, H-2’), 7.47-7.51 (m, 2H, H-3’), 11.89 (br s, 1H, NH); ¹³C NMR (125 MHz, CDCl₃) δ 9.0 (CH₃-4), 9.6 (CH₃-5), 120.8 (C-4), 122.1 (C-5), 129.7 (C-2’), 129.8 (C-3’), 134.8 (C-4’), 135.0 (C-1’), 159.9 (C-2); HRMS (EI) m/z, calcd. for C₁₁H₁₁N₂SCl [M]⁺: 238.0331, found: 238.0322.

1-(3-Chlorophenyl)-4,5-diethyl-1H-imidazole-2(3H)-thione (17a)

Following the method of preparation for 16a, a mixture of 5b (0.150 g, 1.00 mmol) and 15a (0.424 g, 2.50 mmol) afforded 17a (0.194 g, 73%) as a yellow solid; Rf 0.31 (hexane/EtOAc, 1:1); mp 203-204 °C; IR (KBr) ν / cm^-1 3069, 2930, 1651, 1593, 1495, 1394, 1231, 1072, 786, 771, 688; ¹H NMR (300 MHz, CDCl₃) δ 0.85 (t, J 7.5 Hz, 3H, CH₃CH₂-5), 1.21 (t, J 7.7 Hz, 3H, CH₃CH₂-4), 2.32 (q, J 7.5 Hz, 2H, CH₃CH₂-5), 2.50 (q, J 7.7 Hz, 2H, CH₃CH₂-4), 7.25-7.30 (m, 1H, H-6’), 7.33-7.37 (m, 1H, H-4’), 7.44-7.49 (m, 2H, H-2’, H-5’), 12.3 (br s, 1H, NH); ¹³C NMR (75.4 MHz, CDCl₃) δ 14.1 (CH₃CH₂-5), 14.4 (CH₃CH₂-4), 16.9 (CH₃CH₂-5), 17.3 (CH₃CH₂-4), 126.8 (C-4), 127.0 (C-6’), 127.4 (C-5), 128.8 (C-4’), 129.4 (C-2’), 130.3 (C-5’), 134.8 (C-3’), 137.4 (C-1’), 159.7 (C-2); MS (70 eV) m/z, 266 (M⁺, 100), 253 (47), 251 (74), 216 (68), 192 (43), 141 (69), 115 (39); HRMS (EI) m/z, calcd. for C₁₃H₁₅ClN₂S [M]⁺: 266.0644, found: 266.0642; anal. calcd. for C₁₃H₁₅ClN₂S: C, 58.53; H, 5.67; N, 10.50, found: C, 58.58; H, 5.62; N, 10.50.

4,5-Diethyl-1-(m-tolyl)-1H-imidazole-2(3H)-thione (17b)

Following the method of preparation for 16a, a mixture of 5b (0.150 g, 1.00 mmol) and 15b (0.373 g, 2.50 mmol) furnished 17b (0.177 g, 72%) as a yellow solid; Rf 0.38 (hexane/EtOAc, 1:1); mp 182-183 °C; IR (KBr) ν / cm^-1 3152, 3066, 2969, 2928, 1650, 1609, 1590, 1494, 1457, 1395, 1231, 781, 698; ¹H NMR (300 MHz, CDCl₃) δ 0.84 (t, J 7.5 Hz, 3H, CH₃CH₂-5), 1.20 (t, J 7.5 Hz, 3H, CH₃CH₂-4), 2.29 (q, J 7.5 Hz, 2H, CH₃CH₂-5), 2.42 (s, 3H, CH₃-3’), 2.49 (q, J 7.5 Hz, 2H, CH₃CH₂-4), 7.12 (br s, 1H, H-2’), 7.14 (br d, J 7.8 Hz, 1H, H-6’), 7.27 (br d, J 7.8 Hz, 1H, H-4’), 7.41 (t, J 7.8 Hz, 1H, H-5’), 12.30 (br s, 1H, NH); ¹³C NMR (75.4 MHz, CDCl₃) δ 14.2 (CH₃CH₂-5), 14.5 (CH₃CH₂-4), 16.9 (CH₃CH₂-5), 17.3 (CH₃CH₂-4), 21.3 (CH₃-3’), 125.5 (C-6’), 126.4 (C-4), 127.6 (C-5), 128.9 (C 2’), 129.1 (C 5’), 129.8 (C-4’), 136.3 (C-1’), 139.3 (C 3’), 159.2 (C-2); MS (70 eV) m/z, 246 (M⁺, 100), 245 (50), 231 (51), 172 (44), 141 (26), 91 (18); HRMS (EI) m/z, calcd. for C₁₄H₁₈N₂S [M]⁺: 246.1191, found: 246.1194; anal. calcd. for C₁₄H₁₈N₂S: C, 68.25; H, 7.36; N, 11.37, found: C, 68.29; H, 7.32; N, 11.32.

1-(4-Chlorophenyl)-4,5-diethyl-1H-imidazole-2(3H)-thione (17c)

Following the method of preparation for 16a, a mixture of 5b (0.150 g, 1.00 mmol) and 15c (0.424 g, 2.50 mmol) provided 17c (0.205 g, 77%) as a yellow solid; Rf 0.22 (hexane/EtOAc, 1:1); mp 204-205 °C; IR (KBr) ν / cm^-1 3157, 3077, 2970, 2934, 1651, 1496, 1399, 1378, 1231, 1090, 844, 804, 780, 740; ¹H NMR (300 MHz, CDCl₃) δ 0.84 (t, J 7.5 Hz, 3H, CH₃CH₂-5), 1.21 (t, J 7.5 Hz, 3H, CH₃CH₂-4), 2.31 (q, J 7.5 Hz, 2H, CH₃CH₂-5), 2.50 (q, J 7.5 Hz, 2H, CH₃CH₂-4), 7.26-7.33 (m, 2H, H-2’), 7.44-7.47 (m, 2H, H-3’), 12.23 (br s, 1H, NH); ¹³C NMR (75.4 MHz, CDCl₃) δ 14.5 (CH₃CH₂-5), 14.7 (CH₃CH₂-4), 17.2 (CH₃CH₂-5), 17.6 (CH₃CH₂-4), 127.0 (C-4), 127.7 (C-5), 130.0 (C-2’), 130.2 (C-3’), 135.1 (C-1’), 135.3 (C-4’), 159.7 (C-2); MS (70 eV) m/z, 267 (M⁺+1, 30), 266 (M⁺, 100), 265 (26), 251 (58), 216 (32), 141 (45); HRMS (EI) m/z, calcd. for C₁₃H₁₅N₂SCl [M]⁺: 266.0644, found: 266.0645; anal. calcd. for C₁₃H₁₅N₂SCl: C, 58.53; H, 5.67; N, 10.50, found: C, 58.57; H, 5.71; N, 10.47.

1-((1-(3-Chlorophenyl)-4,5-diethyl-1H-imidazol-2-yl)thio)propan-2-one (21a)

In a round-bottomed flask (100 mL), a mixture of 17a (0.322 g, 1.21 mol) and K₂CO₃ (0.167 g, 1.21 mmol) in dry MeOH (20 mL) was stirred at room temperature (rt) for 5 min. Then, 20a (0.112 g, 1.21 mmol) was added and the mixture was stirred at rt for 2 h. The solvent was removed under vacuum and the residue purified by column chromatography over silica gel (20 g/g crude, hexane/EtOAc, 8:2) to produce 21a (0.33 g, 85%) as a yellow oil; Rf 0.50 (hexane/EtOAc, 8:2); IR (film) ν / cm^-1 3443, 2968, 1713, 1593, 1478, 1436, 789, 690; ¹H NMR (300 MHz, CDCl₃) δ 0.88 (t, J 7.5 Hz, 3H, CH₃CH₂-5’), 1.23 (t, J 7.5 Hz, 3H, CH₃CH₂-4’), 2.25 (s, 1H, CH₃CO), 2.40 (q, J 7.5 Hz, 2H, CH₃CH₂-5’), 2.53 (q, J 7.5 Hz, 2H, CH₃CH₂-4’), 3.82 (s, 2H, CH₂S), 7.19 (ddd, J 6.5, 2.1, 1.5 Hz, 1H, H-6”), 7.28-7.31 (m, 1H, H-4”), 7.41-7.49 (m, 2H, H-2”, H-5”); ¹³C NMR (75.4 MHz, CDCl₃) δ 14.5 (CH₃CH₂-5’), 14.6 (CH₃CH₂-4’), 16.9 (CH₃CH₂-5’), 20.4 (CH₃CH₂-4’), 28.6 (CH₃CO), 44.0 (CH₂S), 126.3 (C-6”), 128.1 (C-4”), 129.2 (C-2”), 130.3 (C-5”), 131.3 (C-5’), 134.8 (C-3”), 137.2 (C-1”), 137.8 (C-2’), 140.4 (C-4’), 203.0 (COCH₃); MS (70 eV) m/z, 322 (M⁺, 19), 307 (6), 295 (8), 281 (40), 279 (100), 277 (13), 265 (13), 247 (8), 230 (10), 111 (10); HRMS (EI) m/z, calcd. for C₁₆H₁₉ClN₂OS [M]⁺: 322.0907, found: 322.0901; anal. calcd. for C₁₆H₁₉ClN₂OS: C, 59.52; H, 5.93; N, 8.68; found: C, 59.56; H, 5.94; N, 8.64.

2-((1-(4-Chlorophenyl)-4,5-diethyl-1H-imidazol-2-yl)thio)-1-(4-methoxyphenyl)ethanone (21b)

Following the method of preparation for 21a, a mixture of 17c (0.226 g, 1.00 mmol), K₂CO₃ (0.138 g, 1.00 mmol) and 20b (0.185 g, 1.00 mmol) generated 21b (0.373 g, 90%) as a yellow oil; Rf 0.50 (hexane/EtOAc, 8:2); IR (film) ν / cm^-1 2968, 2931, 1608, 1590, 1491, 1447, 1377, 1233, 779, 726, 700, 658; ¹H NMR (500 MHz, CDCl₃) δ 0.85 (t, J 7.5 Hz, 3H, CH₃CH₂-5’), 1.26 (t, J 7.5 Hz, 3H, CH₃CH₂-4’), 2.36 (q, J 7.5 Hz, 2H, CH₃CH₂-5’), 2.56 (q, J 7.5 Hz, 2H, CH₃CH₂-4’), 3.87 (s, 3H, CH₃O), 4.38 (s, 2H, CH₂S), 6.87-6.91 (m, 2H, H-3”’), 7.02-7.07 (m, 2H, H-2”), 7.34-7.40 (m, 2H, H-3”), 7.82-7.90 (m, 2H, H-2”’); ¹³C NMR (125 MHz, CDCl₃) δ 14.6 (CH₃CH₂-5’), 14.7 (CH₃CH₂-4’), 17.0 (CH₃CH₂-5’), 20.6 (CH₃CH₂-4’), 41.1 (CH₂S), 55.5 (CH₃O), 113.7 (C-3”’), 129.3 (C-2”), 129.4 (C-3”), 129.8 (C-1”’), 131.0 (C-2”’), 131.5 (C-5’), 134.7 (C-1”), 134.8 (C-4”), 138.1 (C-2’), 140.7 (C-4’), 163.8 (C-4”’), 192.8 (COAr); MS (70 eV) m/z, 417 (M⁺+3, 10), 416 (M⁺+2, 16), 415 (M⁺+1, 27), 414 (M⁺, 26), 282 (13), 281 (45), 279 (100), 136 (14), 135 (19), 78 (6); HRMS (EI⁺) m/z, calcd. for C₂₂H₂₃N₂O₂SCl [M]⁺: 414.1169, found: 414.1159.

2-((Chloromethyl)thio)-4,5-diethyl-1-(m-tolyl)-1H-imidazole (21c)

Following the method of preparation for 21a, a mixture of 17b (0.246 g, 1.00 mmol), K₂CO₃ (0.138 g, 1.00 mmol) and 20c (0.085 g, 1.00 mmol) formed 21c (0.265 g, 90%) as a yellow oil; Rf 0.30 (hexane/EtOAc, 8:2); IR (film) ν / cm^-1 2924, 1671, 1599, 1494, 1260, 1171; ¹H NMR (300 MHz, CDCl₃) δ 0.91 (t, J 7.5 Hz, 3H, CH₃CH₂-5), 1.28 (t, J 7.5 Hz, 3H, CH₃CH₂-4), 2.42 (s, 3H, CH₃Ar), 2.43 (q, J 7.5 Hz, 1H, CH₃CH₂-5), 2.61 (q, J 7.5 Hz, 2H, CH₃CH₂-4), 4.94 (s, 2H, SCH₂Cl), 7.03-7.08 (m, 1H, H-6’), 7.06 (br s, 1H, H-2’), 7.29 (br d, J 7.5 Hz, 1H, H-4’), 7.37 (t, J 7.5 Hz, 1H, H-5’); ¹³C NMR (75.4 MHz, CDCl₃) δ 14.5 (CH₃CH₂-5), 14.8 (CH₃CH₂-4), 17.1 (CH₃CH₂-5), 20.7 (CH₃CH₂-4), 21.3 (CH₃-3’), 50.2 (SCH₂Cl), 125.3 (C-6’), 128.8 (C-2’), 128.9 (C-5’), 129.8 (C-4’), 132.4 (C-5), 135.5 (C-3’), 135.9 (C-1’), 139.2 (C-2’), 141.1 (C-4); MS (70 eV) m/z, 297 (M⁺+2, 37), 295 (M⁺+1, 100), 294 (M⁺, 41), 261 (15), 259 (26), 258 (20), 245 (12), 225 (8), 173 (6), 92 (7); HRMS (EI) m/z, calcd. for C₁₅H₁₉N₂SCl [M]⁺: 294.0957, found: 294.0943.

Single crystal X-ray crystallography

Compounds 12c and 16a were obtained as pale yellow crystals and crystallized on a mixture of hexane/EtOAc (8:2), which were mounted on glass fibers. Crystallographic measurements were performed by utilizing an area-detector with Mo Kα radiation (λ = 71073 Å; graphite monochromator) at rt. Unit cell parameters were obtained from a least-squares refinement. Intensities were corrected for Lorentz and polarization effects. Absorption correction was applied by “multi-scan” method. Anisotropic temperature factors were introduced for all non-hydrogen atoms. Hydrogen atoms were placed in idealized positions and their atomic coordinates refined by employing unit weights. After the structure was solved using SHELXT,⁶² it was visualized and plotted on the MERCURY program.⁶³ Data for 12c: (CCDC 2045892) formula: C₂₁H₂₃N₃O₄; molecular weight: 381.42; cryst. syst.: triclinic; space group: P-1 (No. 2); unit cell parameters: a 9.7505(3), b 13.7423(3), c 15.9169(4) Å; α 72.242(2)º, β 87.170(2)º, γ 72.583(2)º; temp.: 292 K; Z: 4; No. of reflections collected: 26381; No. of independent reflections: 12126; No. of reflections observed: 8191; data collection range: 2.7 < θ < 32.5; R: 0.0579; GOF: 1.034. Data for 16a: (CCDC 2045895) formula: C₁₁H₁₁ClN₂S; molecular weight: 238.73; cryst. syst.: triclinic; space group: P-1; unit cell parameters: a 6.6884(5), b 8.5311(8), c 11.7266(8) Å; α 105.893(7)°, β 94.236(6)°, γ 112.533(8)°; temp.: 293 K; Z: 2; No. of reflections collected: 12125; No. of independent reflections: 3880; No. of reflections observed: 2942; data collection range: 3.3 < θ < 32.6; R: 0.0549; GOF: 1.050.

Acknowledgments

We thank Miguel A. Caracas, Pablo Montoya and R. Israel Hernández for their help in the experimental work and Bruce A. Larsen for proofreading. J. T. gratefully acknowledges SIP/IPN (grants 20140858, 20150917, 20160791, 20170902, 20180198, 20195228, 20200227 and 20210700) and CONACYT (grants 43508-Q, 178319, A1-S-17131 and 300520) for financial support. C. E.-H. recognizes CONACYT for a generous grant to purchase the NMR instrument (INFR-2014-01-226114). E. I. M.-M. greatly appreciates the support given by the SEP through the NPTC program (UACOAH-PTC-489). M. A. V. is deeply appreciative of the spectroscopy services provided by the National Laboratory of the Universidad de Guanajuato (UGUAA-CONACYT grant 26073). A. R., R. B., R. U. G., A. M., D. Z-Z. and E. M. L.-M. are beholden to CONACYT for awarding graduate scholarships, and also thank SIP/IPN (BEIFI) and the Ludwig K. Hellweg Foundation for scholarship complements. F. D. and J. T. are fellows of the EDI-IPN and COFAA-IPN programs.

Supplementary Information

Crystallographic data (excluding structure factors) for the structure in this work were deposited in the Cambridge Crystallographic Data Centre as supplementary publication number CCDC 2045892 (for 12c) and CCDC 2045895 (for 16a). Copies of the data can be obtained, free of charge, via www.ccdc.cam.ac.uk/conts/retrieving.html or from the Cambridge Crystallographic Data Centre, CCDC, 12 Union Road, Cambridge CB2 1EZ, UK; fax: [phone]. E-mail: [e-mail].

Supplementary data are available free of charge at http://jbcs.sbq.org.br as PDF file.

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Edited by

Editor handled this article: Teodoro S. Kaufman

Publication Dates

• Publication in this collection
  10 Jan 2022
• Date of issue
  Jan 2022

History

• Received
  10 June 2021
• Accepted
  27 Aug 2021