# Tautomeric Equilibria in Solutions of 2-Phenacylbenzimidazoles

Authors: Agnieszka Skotnicka; Przemysław Czeleń; Ryszard Gawinecki
Journal: Heteroatom Chemistry
 (2019)

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## Abstract

Detailed NMR spectral analysis of DMSO-d6 solutions of the series of substituted 2-phenacylbenzimidazoles (ketimine form,K) reveals two from three tautomeric forms. Integrals of the 1H NMR signals are used in establishing the molar ratio of tautomers. The experimental analyses are supported by quantum-chemical calculations, which satisfactorily reproduced the experimental trends. Although the reported semiempirical quantum-chemical calculations show that enaminoneE, i.e., 2-(1,3-dihydro-2H-benzo[d]imidazol-2-ylidene)-1-phenylethan-1-one, was thermodynamically most stable, the results of MP2ab initiocalculations reveal the following order of stability: ketimine > enolimine > enaminone (substituents do not affect this sequence). 13C CPMAS NMR spectral data reveal that in the crystalline state the enolimine tautomerO is predominant in thep-CH3 andp-NO2 substituted congeners.


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## Body

## 1. Introduction

It was found recently that in chloroform solution 2-phenacylbenzoxazoles (Kin Scheme 1, X = O) are in equilibrium with (Z)-2-(benzo[d]oxazol-2-yl)-1-phenylethenols (enolimines,O) [1]. Strong electron-donating substituents in the benzene ring were found to stabilize theK tautomer. The MP2ab initiocalculations supported the energetic preference of theO (overE) form. 13C CPMAS NMR spectra proved that in the crystalline state the ketimine tautomerK is predominant only in thep-NMe2 substituted congener. On the other hand, enolimine formsO were detected when the substituent had less electron-donating character or when it had an electron-accepting nature [1].Scheme 1
Tautomeric equilibria in some selected 2-phenacyl derivatives of benzoxazole, benzimidazole, and 1-methylbenzimidazole.We have previously shown that 1-methyl-2-phenacylbenzimidazoles are similar in chemical properties to 2-phenacylbenzoxazoles [2]. Analysis of NMR spectra and the results of the quantum-chemical calculations showed unequivocally that 1-methyl-2-phenacylbenzimidazoles (K- form) are in equilibrium with (Z)-2-(1-methyl-1H-benzo[d]imidazol-2-yl)-1-phenylethen-1-ols (O - form).Since the –N=C(–)CH2CO– moiety also is present in 2-phenacylbenzimidazoles (Scheme 1, X = NH), these compounds and 2-phenacylbenzoxazoles and 1-methyl-2-phenacylbenzimidazoles are expected to behave similarly. However, in drawing such conclusions one has to be very careful: minor modifications in the molecule may affect the tautomeric equilibria significantly [1–3]. Such understanding prompted us to see the effect of substitution of the ring oxygen atom in 2-phenacylbenzoxazoles and NCH3 group in 1-methyl-2-phenacylbenzimidazoles by the NH group on their susceptibility to proton transfer.Tautomerism of 2-phenacylbenzimidazoles has been already studied by the NMR methods: 2-phenacylbenzimidazoles (ketiminesK) in DMSO-d6 solution were found to equilibrate with 2-(1,3-dihydro-2H-benzo[d]imidazol-2-ylidene)-1-phenylethan-1-one (enaminones) [4]. Since an unequivocal distinguishing between enoliminesO and enaminonesE (any of these two forms can be present in solution), based only on the simple NMR spectra, may be difficult [1–3],ab initiocalculations were performed in the present paper in order to support or deny the earlier conclusions [4]. The substituent effect on tautomerism of such derivatives is always significant [1–3], so the series of substituted 2-phenacylbenzimidazoles is worth further study.


## 2. Results and Discussion

2-Phenacylbenzimidazoles can be obtained by a variety of methods [5–13]. The aforementioned syntheses are characterized by low yield; therefore, 2-phenacylbenzimidazoles were prepared by treating methylbenzimidazole1 with benzoyl chlorides in the presence of triethylamine followed by thermal decomposition of formed (Z)-2-(1-benzoyl-1H-benzo[d]imidazol-2-yl)-1-phenylvinyl benzoates2a-i (Scheme 2) [5, 7, 11].Scheme 2
Synthesis of 2-phenacylbenzimidazoles.In order to compare 2-phenacylbenzimidazoles with 2-phenacylbenzoxazoles and 1-methyl-2-phenacylbenzimidazoles studied earlier [1, 2], the NMR spectra of the former compounds should be recorded from their deuterated chloroform solutions. Unfortunately, the crystals were sparingly soluble in that solvent, so it was substituted with DMSO-d6.There is a single intramolecular hydrogen bond in 2-phenacylbenzimidazoles [2-(1H-benzo[d]imidazol-2-yl)-1-phenylethan-1-ones] (Scheme 3). In solution, this ketimineK is expected to be in equilibrium with the enolimineO, or enaminoneE tautomers.Scheme 3
Tautomeric equilibria of 2-phenacylbenzimidazoles.Due to the presence of the 2,3-dihydro-2-methylene-1H-benzo[d]imidazole moiety in the molecules, both nitrogen atoms in the enaminone formE are equivalent (unless they are differentiated by the intramolecular hydrogen bond).For the substituents studied, presence of the enolimineO in DMSO-d6 solution has never been reported. 1H and 13C as well as 1H,13C HMBC NMR spectra suggest thatK andE forms are present in such solution [4]. There is no doubt about the presence of the former tautomer, but unequivocal distinguishing between enolimines and enaminones cannot be based only on the simple NMR spectra [1–3]. It is why the 1H,13C HMBC technique has been used earlier to prove which ofK andE is present in solution [4]. Using of the IR spectra to identify the form present in the crystalline stateE [4] also seems unreliable.The chemical shifts of H10 resonances (Table1) are comparable to those observed for 2-phenacyl derivatives of benzoxazoles [1], 1-methy-2-phenacylbenzimidazoles [2], and their enolimine or enaminone tautomers. Thus, the chemical shift values do not reveal whether another tautomer in DMSO-d6 solution isO orE. One should keep in mind that signals of the N-H protons seen at >12 ppm are comparable to those of the hydroxyl protons in the enolimine tautomers of 2-phenacylbenzoxazoles [1].Table 1
Selected1H and 13C NMR chemical shifts for 2-phenacylbenzimidazoles [2-(1H-benzo[d]imidazol-2-yl)-1-phenylethan-1-ones] K and (Z)-2-(1H-benzo[d]imidazol-2-yl)-1-phenylethen-1-ol O (solutions in DMSO-d6, regular characters) and 13C CPMAS spectral data (italics)a.
Comp. Taut. R = H10b H1 and H3 C2 C10 C11 R 2a K p-OCH3 4.66 12.23 137.44 39.85c 193.89 55.71, 56.06d 2a O p-OCH3 6.06 12.39 154.34 79.58 169.62 d 2b K p-CH3 4.64 12.25 137.58 40.03c 195.08 21.41 21.65e 2b O p-CH3 6.07 12.35 154.21 80.51 168.96 e 154.7 77.5 177.2 22.4 2c K m-CH3 4.66 12.33 136.57 40.01c 195.67 21.33, 21.56e 2c O m-CH3 6.10 12.26 154.14 81.30 169.42 e 2d K H 4.68 12.34 136.51 40.12c 195.60 - 2d O H 6.10 12.27 154.11 80.83 169.94 - 2e K p-F 4.67 12.33 135.97 40.09c 194.24 - 2e O p-F 6.00 12.22 153.99 79.12 171.04 - 2f K p-Cl 4.67 12.33 135.20 39.67c 194.06 - 2f O p-Cl 6.03 12.24 153.28 78.89 170.45 - 2g K p-Br 4.67 12.34 135.84 39.80 194.90 - 2g O p-Br 6.03 12.26 153.84 79.38 171.03 2h K m-F 4.70 12.34 135.64 40.26c 194.66 - 2h O m-F 6.05 12.27 153.81 79.54 170.98 - 2i K p-NO2 4.78 12.39 f f f - 2i O p-NO2 6.13 f 153.45 80.33 171.03 - 80.3g 171.1g 152.5 76.5 175.3 aLiterature data collected from DMSO-d6 solutions. bLiterature data: 4.6 ppm - 4.8 ppm for K and 6.0 ppm - 6.25 ppm for E [4–6, 8]. cSince this signal is overlapped by the solvent absorptions, DEPT technique was used to determine its position in the spectrum. dDue to their comparable intensities, the signals cannot be referred to the definite tautomers ([K] ≈ [O], see Table 2). eThe more intense signal was assigned to the O tautomer ([K] < 50 %, see Table 2). fDue to low amount of the K tautomer, these signals were not observed. gLiterature data [4].Table 2
Content of theK form (%) (solutions in DMSO-d6).
Compound Substituent R [K] (%)a,b  2a p-OCH3 49.2 (49.5)c; 50 [4]; 52 [5] 2b p-CH3 32.0 (33.6)c 2c m-CH3 23.1 (24.2)c 2d H 21.9; 20 [4]; 21[5, 7] 2e p-F 21.9 2f p-Cl 13.0; 12 [5] 2g p-Br 15.3 2h m-F 13.0 2i p-NO2 3.9; 2 [4]; 4 [5]; 0 [8] aBased on integrals of the H10 signals (present paper). bLiterature data collected from DMSO-d6 solutions. cValues in parentheses are based on integrals of the substituent protons (CH3, 3.91 ppm for 2a(form K) and 3.87ppm for 2a(formO), 2.51 ppm for 2b(form K) and 2.37 ppm for 2b (form O), 2.51 ppm for 2c(form K) and 2.40 ppm for 2c(form O)).On the other hand, the13C chemical shifts can indicate the tautomer present in solution. C11 signals of other tautomers (O orE) are located in the range of 161-171 ppm (Table 1). Thus, the 2-phenacylbenzimidazolesK are really in equilibrium with theO forms ((Z)-2-(1H-benzo[d]imidazole-2yl)-1-phenylethen-1-ols) [14].The percent content ofK form based on H10 integrals is given in Table 2. The accuracy of these data was supported by the evaluation based on signal intensities of the substituent protons and the literature data. In many cases, mainly π-electron delocalization was found to be responsible for tautomeric preferences but other effects, such as the strength of the intramolecular hydrogen bond, should be taken into account.13C CPMAS spectra of2b and2i show that only one tautomer is present in the solid state. The characteristic chemical shifts of 22.4 ppm (CH3), 77.5 ppm (C10), and 177.2 ppm (C11) for2a and 76.5 ppm (C10) and 175.3 ppm (C11) for2i, suggest that it was the enolimine formO.


### 2.1. Substituent Effect on the Tautomeric Equilibrium

As can be seen in Table2, the tautomeric ratio in solutions of2a-i depends strongly on the substituent. Electron-acceptor substituents increase acidic character of the methylene protons in theK forms and thus favour this tautomer (Scheme 4). In consequence, their proton transfer to theaza atom in these compounds is facile.Scheme 4
Resonance structure contributing to the stabilization of the 2-phenacylbenzimidazole tautomerK by electron-donating substituents.The dependence betweenpKT for 2-phenacylbenzimidazoles and Hammett substituent constant σ [15] has the linear character (pKT = 1.128σ – 0.491, R = 0.977, Figure 1).Figure 1
Plot of -logKTvs. Hammett substituent constants for2a-i.


### 2.2. Quantum-Chemical Calculations

The obtained experimental data seemed worthy of comparison with the results of the respective quantum-chemical calculations. Although semiempirical quantum-chemical calculations show that enaminone formE of2d is thermodynamically more stable than ketimine formK of2d [4], MP2 procedure is recommended as the most accurate and effectiveab initiomethod for studying medium size molecules involving hydrogen bonds [16]. It includes electron correlation so the calculated and experimental data are expected to be comparable [17]. Some optimized bond lengths and dihedral angles in the molecules of 2-phenacylbenzimidazoles and their tautomers are presented in Table 3. Judging from the length of the hydrogen bond, it seems to be stronger in enolimines than in enaminones. Such an interaction is especially weak in ketimines.Table 3
Optimized (MP2/6-311+G(d,p)) bond lengths [Å] and dihedral angles [deg] for 2-phenacylbenzimidazoles and their tautomers.
Comp. Taut. R = N1–H1 O12–H12 N3–H3 O12…H1orN1…H12 H10…H18 Ψ (C14–C13–C11–O12)Ψ (C18–C13–C11–O12) 2a K p-OCH3 1.01 2.70 2.22, 12.25 -  3.70a -165.66 - 2a O p-OCH3 - 1.74 2.29 -29.75 0.99   150.23 1.01 2a E p-OCH3 1.03 1.82 2.25 -28.71 -   150.53 1.01 2d K H 1.01 2.69 2.25, -15.81 -  3.70a 162.48 - 2d O H - 1.74 2.31 -31.42 0.99   148.46 1.01 2d E H 1.03 1.82 2.28 -30.93 -   148.00 1.01 2i K p-NO2 1.01 2.82 2.27, 14.17 -  3.71a -164.73 - 2i O p-NO2 - 1.73 2.26 -28.20 1.00   151.17 1.01 2i E p-NO2 1.03 1.82 2.26 -29.30 -   149.28 1.01 aDistances to H18 from two distinct H10.The effect of the substituent on conformation of each tautomer is negligible. Twisting of the carbonyl group with respect to the neighbouring benzene ring in the ketimine molecules is equal to 10-15° (Table3). The six-membered pseudorings, including the intramolecular hydrogen bonds in both enolimines and enaminones, are almost planar. The dihedral angle (Ψ) between the said benzene ring and C10–C11–O12 moiety in these two tautomers is comparable (ca 30°).Although distances between H18 and methylene protons H10 in 2-phenacylbenzoxazoles were comparable [1], these in 2-phenacylbenzimidazoles (ketimines,K) are significantly differentiated (Table 3) because one of these methylene hydrogens experiences steric hindrance by the aryl ring.The calculated energies of different tautomers (Table4) prove theK form to be the most stable (both electron-donor and electron-acceptor substituents follow this rule).Table 4
MP2(6-311+G(d,p)) calculated relative energies [kJ⋅mol−1] of different tautomers.
Compound Tautomer R = Energy [kJ⋅mol−1]  2a K p-OCH3 0.00a 2a O p-OCH3 10.06 2a E p-OCH3 33.94 2d K H 0.00b 2d O H 6.29 2d E H 30.17 2i K p-NO2 0.00c 2i O p-NO2 2.10 2i E p-NO2 23.05 aAbsolute energy: -875.8329 Hartree. bAbsolute energy: -761.5722 Hartree. cAbsolute energy: -965.6772 Hartree.The enolimineO is always less stable than ketimineK (the more electron-accepting is the substituent, the more stable is the enolimine form). As this can be seen in Scheme 3, the six-membered pseudoring including the NH…O=C system inK is expected to be less aromatic than the respective pseudorings including the NH…O=C and OH…N moieties inE andO, respectively. The strong resonance assisted hydrogen bonds (RAHB), such as this present in the molecule of the later tautomer, are well known [18–21]. The least stable tautomer is alwaysE (both electron-donor and electron-acceptor substituents follow the rule). It is noteworthy thatO seems to be really more stable thanE just because the benzene, pseudo, and imidazole rings are aromatic in the former tautomer, while in the enaminone that is the case for the benzene and pseudorings only (Scheme 3). Thus, from this point of view, 2-phenacylbenzimidazoles resemble 2-phenacylbenzoxazoles [1] and 1-methyl-2-phenylbenzimidazoles [2].


## 2.1. Substituent Effect on the Tautomeric Equilibrium

As can be seen in Table2, the tautomeric ratio in solutions of2a-i depends strongly on the substituent. Electron-acceptor substituents increase acidic character of the methylene protons in theK forms and thus favour this tautomer (Scheme 4). In consequence, their proton transfer to theaza atom in these compounds is facile.Scheme 4
Resonance structure contributing to the stabilization of the 2-phenacylbenzimidazole tautomerK by electron-donating substituents.The dependence betweenpKT for 2-phenacylbenzimidazoles and Hammett substituent constant σ [15] has the linear character (pKT = 1.128σ – 0.491, R = 0.977, Figure 1).Figure 1
Plot of -logKTvs. Hammett substituent constants for2a-i.


## 2.2. Quantum-Chemical Calculations

The obtained experimental data seemed worthy of comparison with the results of the respective quantum-chemical calculations. Although semiempirical quantum-chemical calculations show that enaminone formE of2d is thermodynamically more stable than ketimine formK of2d [4], MP2 procedure is recommended as the most accurate and effectiveab initiomethod for studying medium size molecules involving hydrogen bonds [16]. It includes electron correlation so the calculated and experimental data are expected to be comparable [17]. Some optimized bond lengths and dihedral angles in the molecules of 2-phenacylbenzimidazoles and their tautomers are presented in Table 3. Judging from the length of the hydrogen bond, it seems to be stronger in enolimines than in enaminones. Such an interaction is especially weak in ketimines.Table 3
Optimized (MP2/6-311+G(d,p)) bond lengths [Å] and dihedral angles [deg] for 2-phenacylbenzimidazoles and their tautomers.
Comp. Taut. R = N1–H1 O12–H12 N3–H3 O12…H1orN1…H12 H10…H18 Ψ (C14–C13–C11–O12)Ψ (C18–C13–C11–O12) 2a K p-OCH3 1.01 2.70 2.22, 12.25 -  3.70a -165.66 - 2a O p-OCH3 - 1.74 2.29 -29.75 0.99   150.23 1.01 2a E p-OCH3 1.03 1.82 2.25 -28.71 -   150.53 1.01 2d K H 1.01 2.69 2.25, -15.81 -  3.70a 162.48 - 2d O H - 1.74 2.31 -31.42 0.99   148.46 1.01 2d E H 1.03 1.82 2.28 -30.93 -   148.00 1.01 2i K p-NO2 1.01 2.82 2.27, 14.17 -  3.71a -164.73 - 2i O p-NO2 - 1.73 2.26 -28.20 1.00   151.17 1.01 2i E p-NO2 1.03 1.82 2.26 -29.30 -   149.28 1.01 aDistances to H18 from two distinct H10.The effect of the substituent on conformation of each tautomer is negligible. Twisting of the carbonyl group with respect to the neighbouring benzene ring in the ketimine molecules is equal to 10-15° (Table3). The six-membered pseudorings, including the intramolecular hydrogen bonds in both enolimines and enaminones, are almost planar. The dihedral angle (Ψ) between the said benzene ring and C10–C11–O12 moiety in these two tautomers is comparable (ca 30°).Although distances between H18 and methylene protons H10 in 2-phenacylbenzoxazoles were comparable [1], these in 2-phenacylbenzimidazoles (ketimines,K) are significantly differentiated (Table 3) because one of these methylene hydrogens experiences steric hindrance by the aryl ring.The calculated energies of different tautomers (Table4) prove theK form to be the most stable (both electron-donor and electron-acceptor substituents follow this rule).Table 4
MP2(6-311+G(d,p)) calculated relative energies [kJ⋅mol−1] of different tautomers.
Compound Tautomer R = Energy [kJ⋅mol−1]  2a K p-OCH3 0.00a 2a O p-OCH3 10.06 2a E p-OCH3 33.94 2d K H 0.00b 2d O H 6.29 2d E H 30.17 2i K p-NO2 0.00c 2i O p-NO2 2.10 2i E p-NO2 23.05 aAbsolute energy: -875.8329 Hartree. bAbsolute energy: -761.5722 Hartree. cAbsolute energy: -965.6772 Hartree.The enolimineO is always less stable than ketimineK (the more electron-accepting is the substituent, the more stable is the enolimine form). As this can be seen in Scheme 3, the six-membered pseudoring including the NH…O=C system inK is expected to be less aromatic than the respective pseudorings including the NH…O=C and OH…N moieties inE andO, respectively. The strong resonance assisted hydrogen bonds (RAHB), such as this present in the molecule of the later tautomer, are well known [18–21]. The least stable tautomer is alwaysE (both electron-donor and electron-acceptor substituents follow the rule). It is noteworthy thatO seems to be really more stable thanE just because the benzene, pseudo, and imidazole rings are aromatic in the former tautomer, while in the enaminone that is the case for the benzene and pseudorings only (Scheme 3). Thus, from this point of view, 2-phenacylbenzimidazoles resemble 2-phenacylbenzoxazoles [1] and 1-methyl-2-phenylbenzimidazoles [2].


## 3. Experimental Methods

Melting points were measured on a Boetius table and are uncorrected. Satisfactory elemental analyses (± 0.30 % for C, H and N) were obtained from Perkin Elmer 2400 Series II CHNS/O.


### 3.1. Syntheses: General Procedure

Benzoyl chloride (0.04 mole) was added in one portion to the stirred solution of 2-methylbenzimidazole1 (1.46 g, 0.01 mole) and triethylamine (5.6 mL, 4.05 g, 0.04 mole) in diglyme (4 mL). Content of the reaction vessel was heated for 1 h on the boiling water bath. Dropwise addition of water (60 mL) to the stirred cold reaction mixture resulted in precipitation of (Z)-2-(1H-benzo[d]imidazol-2-yl)-1-phenylvinyl benzoates. A solution of the crude material (0.006 mole) and morpholine (1.6 mL, 1,57 g, 0.018 mole) in methanol (9 mL) were heated under reflux with stirring for 10 min. Water (9 mL) was added to the boiling reaction mixture, which cooled to start precipitation. Crystallization of the collected solid from methanol affords pure 2-phenacylbenzimidazoles2a-i.2-(1H-benzimidazol-2-yl)-1-(4-methoxyphenyl)ethan-1-one (2a). Yellow solid; yield 0.66 g (57%); mp 205-207°C (lit. 205-207 [22], 208-209°C [4, 5]); 1H NMR (DMSO-d6 from TMS) δ 3.87 (3H, s,p-OCH3 (O)), 3.91 (3H, s,p-OCH3 (K)), 4.66 (2H, s, CH2CO (K)), 6.06 (1H, s, CHO (O)), 7.07 (2H, m (O)), 7.15 (2H, m, (O)), 7.21 (4H, m, (K)), 7.43 (1H, m, (O)), 7.58 (3H, m, (O)), 7.88 (2H, m, (K)), 8.14 (2H, m, (K)), 12.24 (1H, s, NH (K)), 12.39 (1H, s, NH (O)). 13C NMR δ 39.85, 55.71, 56.06, 79.72, 110.82, 114.21, 114.49, 114.93, 115.32, 121.80, 122.39, 127.63, 129.42, 129.96, 131.36, 132.30, 132.62, 137.44, 149.57, 154.34, 161.06, 163.95, 169,62, 193.89. Anal. Calcd for C16H14N2O2: C, 72.16; H, 5.30; N, 10.52. Found: C, 72.21; H, 5.15, 10.18.2-(1H-benzimidazol-2-yl)-1-(4-methylphenyl)ethan-1-one (2b). Yellow solid; yield 0.97 g (65%); mp 192-193.5°C (lit. 195-196°C [4]); 1H NMR (DMSO-d6 from TMS) δ 2.37 (3H, s,p-CH3 (O)), 2.51 (3H, s,p-CH3 (K)), 4.64 (2H, s, CH2CO (K)), 6.07 (1H, s, CHO (O)), 7.16 (3H, m (O)), 7.27 (2H, d, 3JH,H= 7.96 Hz, (O)), 7.38 (4H, m (K)), 7.50 (1H, m (O)), 7.57 (2H, m (K)), 7.76 (2H, m (O)), 8.00 (2H, m (K)), 12.25 (1H, s, NH (K)), 12.35 1H, s, NH (O)). 13C NMR δ 21.40, 21.64, 40.03, 80.64, 110.90, 115.13, 122.37, 122.57, 125.96, 129.07, 129.47, 129.83, 130.17, 130.47, 132.30, 134.03, 134.67, 137.58, 139.87, 144.58, 149.42, 154.21, 169.45, 195.08. Anal. Calcd for C16H14N2O: C, 76.78; H, 5.64; N, 11.19. Found: C, 76.81; H, 5.52; N, 11.09.2-(1H-benzimidazol-2-yl)-1-(3-methylphenyl)ethan-1-one (2c). Yellow solid; yield 1.11 g (70%); mp 166-171°C (lit. 142-143°C [22]); 1H NMR (DMSO-d6 from TMS) δ 2.40 (3H, s,m-CH3 (O)), 2.51 (3H, s,m-CH3 (K)), 4.66 (2H, s, CH2CO (K)), 6.66 (1H, s, CHO (O)), 7.16 (3H, m (O)), 7.26 (3H, d 3JH,H= 7.48 Hz, (K)), 7.35 (3H, t (K)), 7.47 (3H, m (O)), 7.66 (2H, m (O)), 7.89 (2H, d 3JH,H= 7.36 Hz, (K)), 12.26 (1H, s, NH (O)), 12.33 (1H, s, NH (K)). 13C NMR δ 21.33, 21.56, 40.10, 81.30, 110.99, 115.26, 121.83, 122.53, 123.20, 126.23, 126.50, 126.76, 128.79, 129.15, 129.24, 130.84, 132.36, 134.68, 136.57, 137.40, 138.02, 138.69, 149.37, 154.14, 169.42, 195.67. Anal. Calcd for C16H14N2O: C, 76.78; H, 5.64; N, 11.19. Found: C, 76.58; H, 5.58; N, 10.91.2-(1H-benzimidazol-2-yl)-1-phenylethan-1-one (2d). Light yellow solid; yield 1.22 g (87%); mp 182-183°C (lit. 176-178 [22], 179 [6], 178-178.5 [7], 178-179°C [4]); 1H NMR (DMSO-d6 from TMS) δ 4.68 (2H, s, CH2CO (K)), 6.10 (1H, s, CHO (O)), 7.17 (3H, m (O)), 7.42 (1H, m (O)), 7.45 (2H, m (O)), 7.49 (1H, m (K)), 7.57 (5H, m (K)), 7.68 (1H, m (K)), 7.86 (2H, m (O)), 8. 09 (2H, m (K)), 12.27 (1H, s, NH (O)), 12.34 (1H, s, NH (K)). 13C NMR δ 40.12, 80.83, 110.95, 115.06, 121.86, 122.51, 126.01, 128.88, 128.94, 129.28, 130.17, 132.25, 134.08, 136.51, 137.23, 137.63, 149.31, 154.11, 169.94, 195.60. Anal. Calcd for C15H12N2O: C, 74.22; H, 5.13; N, 10.18. Found: C, 74.35; H, 4.97; N, 10.23.2-(1H-benzimidazol-2-yl)-1-(4-fluorophenyl)ethan-1-one (2e). Brownish solid; yield 0.74 g (59%); mp 196-200°C (lit. 204-205°C [22]; 1H NMR (DMSO-d6 from TMS) δ 4.67 (2H, s, CH2CO (K)), 6.67 (1H, s, CHO (O)), 7.17 (3H, m (O)), 7.28 (2H, m (O)), 7.38 (1H, m (O)), 7.43 (2H, m (K)), 7.55 (4H, m (K)), 7.91 (2H, m (O)), 8.18 (2H, m (K)), 12.22 (1H, s, NH (O)), 12.33 (1H, s, NH (K)). 13C NMR δ 40.09, 79.12, 110.82, 114.43, 115.54, 115.76, 116.22, 116.44, 121.91, 122.61, 128.42, 128.51, 131.97, 132.07, 133.23, 133.26, 134.92, 134.95, 135.97, 149.20, 153.99, 162.26, 164.47, 164.71, 166.98, 171.04, 194.24. Anal. Calcd for C15H11FN2O: C, 73.26; H, 4.99; N, 10.05. Found: C, 73.04; H, 5.16; N, 10.02.2-(1H-benzimidazol-2-yl)-1-(4-chlorophenyl)ethan-1-one (2f). Yellow solid; yield 1.05 g (68%); mp 232-234°C (lit. 226-228°C [4, 5]; 1H NMR (DMSO-d6 from TMS) δ 4.67 (2H, s, CH2CO (K)), 6.03 (1H, s, CHO (O)), 7.14 (3H, m (K)), 7.19 (2H, m (O)), 7.48 (4H, m, (O)), 7.63 (3H, d, 3JH,H= 8.40 Hz, (K)), 7.68 (2H, d, 3JH,H= 8.40 Hz, (O)), 8.40 (2H, d, 3JH,H= 8.40 Hz, (K)), 12.24 (1H, s, NH (O)), 12.33 (1H, s, NH (K)). 13C NMR δ 39.67, 78.89, 110.33, 113.91, 121.33, 122.12, 127.42, 128.28, 128.84, 130.31, 131.38, 134.16, 134.58, 135.20, 136.78, 138.51, 148.54, 153.28, 170.45, 194.06. Anal. Calcd for C15H11ClN2O: C, 72.41; H, 4.93; N, 9.93. Found: C, 72.46; H, 4.88; N, 9.86.2-(1H-benzimidazol-2-yl)-1-(4-bromophenyl)ethan-1-one (2g).Yellow solid; yield 1.48 g (82%); mp 193-195°C (lit. 238-240 [22], 244-246°C [4]); 1H NMR (DMSO-d6 from TMS) δ 4.67 (2H, s, CH2CO (K)), 6.03 (1H, s, CHO (O)), 7.17 (2H, m (O)), 7.37 (3H, s (K)), 7.56 (3H, s (K)), 7.66 (3H, m (O)), 7.80 (3H, m (O)), 8.01(2H, m (K)), 12.26 (1H, s NH (O)), 12.34 (1H, s, NH (K)). 13C NMR δ 39.80,79.38, 110.89, 111.49, 114.45, 121.47, 122.30, 122.54, 122.80, 123.49, 128.23, 130.97, 131.77, 132.37, 133.13, 135.50, 135.84, 137.67, 149.06, 153.84, 171.03, 194.90. Anal. Calcd for C15H11BrN2O: C, 70.19; H, 4.78; N, 9.63. Found: C, 68.99; H, 4.83; N, 9.47.2-(1H-benzimidazol-2-yl)-1-(3-fluorophenyl)ethan-1-one (2h). Yellow solid; yield 1.32 g (77%); mp 211-213°C; 1H NMR (DMSO-d6 from TMS) δ 4.70 (2H, s, CH2CO (K)), 6.05 (1H, s, CHO (O)), 7.17 (2H, m (O)), 7.19 (3H, m (K)), 7.28 (1H, m (O)), 7.38 (1H, m (O)), 7.49 (3H, m (K)), 7.51 (1H, m (O)), 7.57 (1H, m (O)), 7.61 (1H, m (O)), 7.64 (2H, m (K)), 7.70 (1H, m (O)), 12.27 (1H, s, NH (O)), 12.34 (1H, s, NH (K)). 13C NMR δ 40.26, 79.54, 110.94, 112.63, 112.85, 114.38, 115.33, 115.55, 116.66, 116.87, 120.89, 121.10, 122.18, 122.72, 125.17, 130.79, 131.49, 131.93, 135.64, 141.34, 149.02, 153.81, 161.63, 164.05, 170.98, 194.66. Anal. Calcd for C15H11FN2O: C, 73.26; H, 4.99; N, 10.05. Found: C, 73.37; H, 5.11; N, 10.22.2-(1H-benzimidazol-2-yl)-1-(4-nitrophenyl)ethan-1-one (2i). Orange solid; yield 1.7 g (95%); mp 159-161 (lit. 165-166 [8], 270-272 [22], 295-297°C [4, 5]); 1H NMR (DMSO-d6 from TMS) δ 6.13 (1H, s, CHO (O)), 7.20 (2H, m (O)), 7.41 (1H, s (O)), 7.59 (1H, s (O)), 8.11 (2H, m (O)), 8.30 (2H, m (O)), 12.39 (1H, s NH (O)).13C NMR δ 80.32, 111.06, 114.25, 122.99, 124.07, 131.75, 134.89, 145.06, 148.25, 153.45, 171.03. Anal. Calcd for C15H11N3O3: C, 71.87; H, 4.90; N, 10.85. Found: C, 71.77; H, 5.10; N, 10.94.


### 3.2. NMR Spectral Analysis

The1H and 13C NMR spectra were recorded for diluted DMSO-d6 solution at 298 K on a Bruker Ascend 400 MHz spectrometer. The chemical shifts are referenced to the signal of internal TMS at δ=0.00 ppm. The 1H, 13C and PFG 1H,13C HMQC and HMBC spectra were recorded on a Bruker Avance DRX 500 spectrometer equipped with an inverse detection probehead and z-gradient accessory working at 500.13 MHz and 125.77 MHz, respectively. The number of data points in PFG 1H,13C HMQC and HMBC measurements were 1024 (f2) x 256 (f1). This matrix was zero filled to 2048 x 512 and apodized by a shifted sine bell window function along both axes prior to FT.The solid state13C CPMAS NMR spectra were recorded on a Bruker Avance 400 FT NMR spectrometer using the samples packed in 4.0 mm o.d. zirconia rotors. The samples were spun at 10 KHz rate and >1000 transients were accumulated. The FIDs are apodized by 10 Hz exponential window before FT. The shifts are referenced to the C=O signal of glycine standard at δ=176.03 ppm.


### 3.3. Quantum-Chemical Calculations

Geometries for the isolated molecules (vacuum) of the tautomers were optimized using the second order Möller-Plesset method (MP2) [23, 24]. Computations were carried out utilizing the split-valence triple-zeta basis sets 6-311+G(d,p) [25]. All calculations were realized with use of Gaussian 09 package [26].


## 3.1. Syntheses: General Procedure

Benzoyl chloride (0.04 mole) was added in one portion to the stirred solution of 2-methylbenzimidazole1 (1.46 g, 0.01 mole) and triethylamine (5.6 mL, 4.05 g, 0.04 mole) in diglyme (4 mL). Content of the reaction vessel was heated for 1 h on the boiling water bath. Dropwise addition of water (60 mL) to the stirred cold reaction mixture resulted in precipitation of (Z)-2-(1H-benzo[d]imidazol-2-yl)-1-phenylvinyl benzoates. A solution of the crude material (0.006 mole) and morpholine (1.6 mL, 1,57 g, 0.018 mole) in methanol (9 mL) were heated under reflux with stirring for 10 min. Water (9 mL) was added to the boiling reaction mixture, which cooled to start precipitation. Crystallization of the collected solid from methanol affords pure 2-phenacylbenzimidazoles2a-i.2-(1H-benzimidazol-2-yl)-1-(4-methoxyphenyl)ethan-1-one (2a). Yellow solid; yield 0.66 g (57%); mp 205-207°C (lit. 205-207 [22], 208-209°C [4, 5]); 1H NMR (DMSO-d6 from TMS) δ 3.87 (3H, s,p-OCH3 (O)), 3.91 (3H, s,p-OCH3 (K)), 4.66 (2H, s, CH2CO (K)), 6.06 (1H, s, CHO (O)), 7.07 (2H, m (O)), 7.15 (2H, m, (O)), 7.21 (4H, m, (K)), 7.43 (1H, m, (O)), 7.58 (3H, m, (O)), 7.88 (2H, m, (K)), 8.14 (2H, m, (K)), 12.24 (1H, s, NH (K)), 12.39 (1H, s, NH (O)). 13C NMR δ 39.85, 55.71, 56.06, 79.72, 110.82, 114.21, 114.49, 114.93, 115.32, 121.80, 122.39, 127.63, 129.42, 129.96, 131.36, 132.30, 132.62, 137.44, 149.57, 154.34, 161.06, 163.95, 169,62, 193.89. Anal. Calcd for C16H14N2O2: C, 72.16; H, 5.30; N, 10.52. Found: C, 72.21; H, 5.15, 10.18.2-(1H-benzimidazol-2-yl)-1-(4-methylphenyl)ethan-1-one (2b). Yellow solid; yield 0.97 g (65%); mp 192-193.5°C (lit. 195-196°C [4]); 1H NMR (DMSO-d6 from TMS) δ 2.37 (3H, s,p-CH3 (O)), 2.51 (3H, s,p-CH3 (K)), 4.64 (2H, s, CH2CO (K)), 6.07 (1H, s, CHO (O)), 7.16 (3H, m (O)), 7.27 (2H, d, 3JH,H= 7.96 Hz, (O)), 7.38 (4H, m (K)), 7.50 (1H, m (O)), 7.57 (2H, m (K)), 7.76 (2H, m (O)), 8.00 (2H, m (K)), 12.25 (1H, s, NH (K)), 12.35 1H, s, NH (O)). 13C NMR δ 21.40, 21.64, 40.03, 80.64, 110.90, 115.13, 122.37, 122.57, 125.96, 129.07, 129.47, 129.83, 130.17, 130.47, 132.30, 134.03, 134.67, 137.58, 139.87, 144.58, 149.42, 154.21, 169.45, 195.08. Anal. Calcd for C16H14N2O: C, 76.78; H, 5.64; N, 11.19. Found: C, 76.81; H, 5.52; N, 11.09.2-(1H-benzimidazol-2-yl)-1-(3-methylphenyl)ethan-1-one (2c). Yellow solid; yield 1.11 g (70%); mp 166-171°C (lit. 142-143°C [22]); 1H NMR (DMSO-d6 from TMS) δ 2.40 (3H, s,m-CH3 (O)), 2.51 (3H, s,m-CH3 (K)), 4.66 (2H, s, CH2CO (K)), 6.66 (1H, s, CHO (O)), 7.16 (3H, m (O)), 7.26 (3H, d 3JH,H= 7.48 Hz, (K)), 7.35 (3H, t (K)), 7.47 (3H, m (O)), 7.66 (2H, m (O)), 7.89 (2H, d 3JH,H= 7.36 Hz, (K)), 12.26 (1H, s, NH (O)), 12.33 (1H, s, NH (K)). 13C NMR δ 21.33, 21.56, 40.10, 81.30, 110.99, 115.26, 121.83, 122.53, 123.20, 126.23, 126.50, 126.76, 128.79, 129.15, 129.24, 130.84, 132.36, 134.68, 136.57, 137.40, 138.02, 138.69, 149.37, 154.14, 169.42, 195.67. Anal. Calcd for C16H14N2O: C, 76.78; H, 5.64; N, 11.19. Found: C, 76.58; H, 5.58; N, 10.91.2-(1H-benzimidazol-2-yl)-1-phenylethan-1-one (2d). Light yellow solid; yield 1.22 g (87%); mp 182-183°C (lit. 176-178 [22], 179 [6], 178-178.5 [7], 178-179°C [4]); 1H NMR (DMSO-d6 from TMS) δ 4.68 (2H, s, CH2CO (K)), 6.10 (1H, s, CHO (O)), 7.17 (3H, m (O)), 7.42 (1H, m (O)), 7.45 (2H, m (O)), 7.49 (1H, m (K)), 7.57 (5H, m (K)), 7.68 (1H, m (K)), 7.86 (2H, m (O)), 8. 09 (2H, m (K)), 12.27 (1H, s, NH (O)), 12.34 (1H, s, NH (K)). 13C NMR δ 40.12, 80.83, 110.95, 115.06, 121.86, 122.51, 126.01, 128.88, 128.94, 129.28, 130.17, 132.25, 134.08, 136.51, 137.23, 137.63, 149.31, 154.11, 169.94, 195.60. Anal. Calcd for C15H12N2O: C, 74.22; H, 5.13; N, 10.18. Found: C, 74.35; H, 4.97; N, 10.23.2-(1H-benzimidazol-2-yl)-1-(4-fluorophenyl)ethan-1-one (2e). Brownish solid; yield 0.74 g (59%); mp 196-200°C (lit. 204-205°C [22]; 1H NMR (DMSO-d6 from TMS) δ 4.67 (2H, s, CH2CO (K)), 6.67 (1H, s, CHO (O)), 7.17 (3H, m (O)), 7.28 (2H, m (O)), 7.38 (1H, m (O)), 7.43 (2H, m (K)), 7.55 (4H, m (K)), 7.91 (2H, m (O)), 8.18 (2H, m (K)), 12.22 (1H, s, NH (O)), 12.33 (1H, s, NH (K)). 13C NMR δ 40.09, 79.12, 110.82, 114.43, 115.54, 115.76, 116.22, 116.44, 121.91, 122.61, 128.42, 128.51, 131.97, 132.07, 133.23, 133.26, 134.92, 134.95, 135.97, 149.20, 153.99, 162.26, 164.47, 164.71, 166.98, 171.04, 194.24. Anal. Calcd for C15H11FN2O: C, 73.26; H, 4.99; N, 10.05. Found: C, 73.04; H, 5.16; N, 10.02.2-(1H-benzimidazol-2-yl)-1-(4-chlorophenyl)ethan-1-one (2f). Yellow solid; yield 1.05 g (68%); mp 232-234°C (lit. 226-228°C [4, 5]; 1H NMR (DMSO-d6 from TMS) δ 4.67 (2H, s, CH2CO (K)), 6.03 (1H, s, CHO (O)), 7.14 (3H, m (K)), 7.19 (2H, m (O)), 7.48 (4H, m, (O)), 7.63 (3H, d, 3JH,H= 8.40 Hz, (K)), 7.68 (2H, d, 3JH,H= 8.40 Hz, (O)), 8.40 (2H, d, 3JH,H= 8.40 Hz, (K)), 12.24 (1H, s, NH (O)), 12.33 (1H, s, NH (K)). 13C NMR δ 39.67, 78.89, 110.33, 113.91, 121.33, 122.12, 127.42, 128.28, 128.84, 130.31, 131.38, 134.16, 134.58, 135.20, 136.78, 138.51, 148.54, 153.28, 170.45, 194.06. Anal. Calcd for C15H11ClN2O: C, 72.41; H, 4.93; N, 9.93. Found: C, 72.46; H, 4.88; N, 9.86.2-(1H-benzimidazol-2-yl)-1-(4-bromophenyl)ethan-1-one (2g).Yellow solid; yield 1.48 g (82%); mp 193-195°C (lit. 238-240 [22], 244-246°C [4]); 1H NMR (DMSO-d6 from TMS) δ 4.67 (2H, s, CH2CO (K)), 6.03 (1H, s, CHO (O)), 7.17 (2H, m (O)), 7.37 (3H, s (K)), 7.56 (3H, s (K)), 7.66 (3H, m (O)), 7.80 (3H, m (O)), 8.01(2H, m (K)), 12.26 (1H, s NH (O)), 12.34 (1H, s, NH (K)). 13C NMR δ 39.80,79.38, 110.89, 111.49, 114.45, 121.47, 122.30, 122.54, 122.80, 123.49, 128.23, 130.97, 131.77, 132.37, 133.13, 135.50, 135.84, 137.67, 149.06, 153.84, 171.03, 194.90. Anal. Calcd for C15H11BrN2O: C, 70.19; H, 4.78; N, 9.63. Found: C, 68.99; H, 4.83; N, 9.47.2-(1H-benzimidazol-2-yl)-1-(3-fluorophenyl)ethan-1-one (2h). Yellow solid; yield 1.32 g (77%); mp 211-213°C; 1H NMR (DMSO-d6 from TMS) δ 4.70 (2H, s, CH2CO (K)), 6.05 (1H, s, CHO (O)), 7.17 (2H, m (O)), 7.19 (3H, m (K)), 7.28 (1H, m (O)), 7.38 (1H, m (O)), 7.49 (3H, m (K)), 7.51 (1H, m (O)), 7.57 (1H, m (O)), 7.61 (1H, m (O)), 7.64 (2H, m (K)), 7.70 (1H, m (O)), 12.27 (1H, s, NH (O)), 12.34 (1H, s, NH (K)). 13C NMR δ 40.26, 79.54, 110.94, 112.63, 112.85, 114.38, 115.33, 115.55, 116.66, 116.87, 120.89, 121.10, 122.18, 122.72, 125.17, 130.79, 131.49, 131.93, 135.64, 141.34, 149.02, 153.81, 161.63, 164.05, 170.98, 194.66. Anal. Calcd for C15H11FN2O: C, 73.26; H, 4.99; N, 10.05. Found: C, 73.37; H, 5.11; N, 10.22.2-(1H-benzimidazol-2-yl)-1-(4-nitrophenyl)ethan-1-one (2i). Orange solid; yield 1.7 g (95%); mp 159-161 (lit. 165-166 [8], 270-272 [22], 295-297°C [4, 5]); 1H NMR (DMSO-d6 from TMS) δ 6.13 (1H, s, CHO (O)), 7.20 (2H, m (O)), 7.41 (1H, s (O)), 7.59 (1H, s (O)), 8.11 (2H, m (O)), 8.30 (2H, m (O)), 12.39 (1H, s NH (O)).13C NMR δ 80.32, 111.06, 114.25, 122.99, 124.07, 131.75, 134.89, 145.06, 148.25, 153.45, 171.03. Anal. Calcd for C15H11N3O3: C, 71.87; H, 4.90; N, 10.85. Found: C, 71.77; H, 5.10; N, 10.94.


## 3.2. NMR Spectral Analysis

The1H and 13C NMR spectra were recorded for diluted DMSO-d6 solution at 298 K on a Bruker Ascend 400 MHz spectrometer. The chemical shifts are referenced to the signal of internal TMS at δ=0.00 ppm. The 1H, 13C and PFG 1H,13C HMQC and HMBC spectra were recorded on a Bruker Avance DRX 500 spectrometer equipped with an inverse detection probehead and z-gradient accessory working at 500.13 MHz and 125.77 MHz, respectively. The number of data points in PFG 1H,13C HMQC and HMBC measurements were 1024 (f2) x 256 (f1). This matrix was zero filled to 2048 x 512 and apodized by a shifted sine bell window function along both axes prior to FT.The solid state13C CPMAS NMR spectra were recorded on a Bruker Avance 400 FT NMR spectrometer using the samples packed in 4.0 mm o.d. zirconia rotors. The samples were spun at 10 KHz rate and >1000 transients were accumulated. The FIDs are apodized by 10 Hz exponential window before FT. The shifts are referenced to the C=O signal of glycine standard at δ=176.03 ppm.


## 3.3. Quantum-Chemical Calculations

Geometries for the isolated molecules (vacuum) of the tautomers were optimized using the second order Möller-Plesset method (MP2) [23, 24]. Computations were carried out utilizing the split-valence triple-zeta basis sets 6-311+G(d,p) [25]. All calculations were realized with use of Gaussian 09 package [26].


## 4. Conclusions

In DMSO-d6 solution, 2-phenacylbenzimidazoles (ketimine tautomeric form,K) are in equilibrium with (Z)-2-(1H-benzo[d]imidazol-2-yl)-1-phenylethen-1-ol (enolimine form,O). 2-(1H-benzo[d]imidazol-2(3H)-ylidene-1-phenylethanones (enaminonesE) were not detected (our findings are different from those reported earlier by other authors [4]). The molar ratio of different forms in solution (based on the integrals of 1H NMR signals) depends on substituent. Electron-acceptor substituents increase the acidic character of the methylene protons in the ketimine formsK. In consequence, the transfer of such a proton to the carbonyl oxygen is very easy in these compounds. The calculated energies of different tautomers prove the ketimine formK including the OH…N hydrogen bond to be the most stable (both electron-donor and electron-acceptor substituents follow this rule). The enolimine tautomersO are always less stable than ketiminesK. The most labile tautomer is always enaminoneE. Enolimine tautomersO were detected by solid state 13C CPMAS NMR.



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*Source: 4364207-2019-02-03.xml*