Spectral evidence for generic charge → acceptor interactions in carbamates and esters

The correlations of the 1H NMR, 13C NMR and FT-IR spectral data from the R–O–C 
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Created by potrace 1.16, written by Peter Selinger 2001-2019
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 O groups in the alkyl carbamates and esters of homologous alcohols reveal R-group-dependent negative charge stabilization at the carbonyl oxygen and their donation to generic acceptors at Cα of even alkyl alcohols (R), which explains several of their apparently anomalous properties.

Electronic interactions at the R-O-C]O groups in carbamates and esters are less understood than that at the R-N-C]O groups in amides. Carbamates in which both these groups are fused at the carbonyl C]O bond, have several ester-like rather than amide-like features 1,2 including comparable C-O bond lengths in crystals, [3][4][5][6] favourable interactions between the dipoles of the C]O and O-R bonds in the predominant s-trans rotamers of the R-O-C]O groups and unfavourable lone pair repulsion between the two ester oxygens in their trace s-cis rotamers [7][8][9][10] (Fig. 1a). However, several anomalous properties of carbamates and esters cannot be explained by these dipole and repulsive forces alone. For example, despite the electronic resonance at the O-C]O group in esters and additionally at the N-C]O group in carbamates (both of which augment the electron density at their carbonyl oxygens), their carbonyls have remarkably lower basicities than the carbonyls of amides 11 and even those of ketones, which lack such resonance effects. 12 The barriers to the C-N bond rotation for carbamates are 3-4 kcal mol À1 lower than those for analogous amides. 13,14 Carbamate and ester carbonyl oxygens also have poor hydrogen bond accepting propensities compared to amides. [15][16][17][18][19][20] Of particular current interest is the apparent anomaly that in the crystals of phenyl carbamates, the phenyl ring plane is oriented perpendicular to the carbamate plane 21,22 (Fig. 1b). The presence of an extraordinary n / p* orbital overlap interaction (O/C a phenyl ) between the lone-pair electrons on the carbonyl (C]O) oxygen and the p* orbital of the phenyl ring has been proposed as the stabilizing force for this conformer based on natural bond orbital (NBO) analysis. 22 This is interesting for several reasons: (i) despite a decrease in the stretching frequency of C]O in the FT-IR spectrum for this conformer, which indicates a decrease in the bond order and concomitant improvement in the charge density at the carbonyl oxygen, a discussion on the origin and role of such charge on this O/ C a alcohol interaction is lacking. Rather, the interaction is assumed to originate from the lone pair on oxygen. (ii) Our investigation of CCDC revealed that the O/C a alcohol distances at the C a -O-C]O groups are quite non-variant (2.62-2.81 A) for  (9)(10)(11)(12)(13)(14)(15)(16) and alcohols (17)(18)(19)(20) investigated. HCR is hyperconjugative resonance along the C a -C b bond of alcohol groups in carbamates and esters. both aliphatic and aromatic carbamates and esters, [3][4][5][6][23][24][25][26][27] notwithstanding the variations in the structure resolutions. These invoked the following questions: is the O/C a interaction specic to the p* acceptors at C a alcohol ? Can any antibonding orbital at C a alcohol act as an acceptor of the electrons from carbonyl oxygen? What is the generic nature and role of this O/ C a interaction in the C a -O-C]O groups? Here, we present the rst spectral evidence for the generic nature of the O/C a interactions even with non-p* orbital acceptors (like s* and hyperconjugative resonance bonds) at C a in the C a -O-C]O groups (Fig. 1c) of a variety of model homologous aliphatic carbamates and esters (Fig. 1d). The charge at the carbonyl oxygen is interdependent on the alkoxy groups and forms charge / acceptor O/C a interactions, which inuence the rotational states of the O-C a bonds in the carbamates and esters.
To explore the possibility of the O/C a interactions at C a -O-C]O in aliphatic carbamates and esters, we investigated the 1 H NMR, 13 C NMR and FT-IR spectra of the secondary and tertiary carbamates (1-4 and 5-8), acetates (9-12) and benzoates (13)(14)(15)(16) of homologous aliphatic alcohols (H-C a H 2 -OH, MeOH; CH 3 -C a H 2 -OH, ethanol; (CH 3 ) 2 -C a H-OH, isopropanol; and (CH 3 ) 3 -C a -OH, tert-butanol, 17-20) (Table 1) and correlated their deviations from those of their corresponding alcohols. These are ideal models to investigate the fundamental nature and origin of the O/C a interactions because on increasing the methyl substitution at C a , there is a systematic increase in the C a electron density, thus progressively diminishing its electron acceptor propensity. Any O/C a donor-acceptor interactions will thus have least assistance from other local electronic effects. Evidence for the O/C a interactions with such electronically and sterically antagonistic aliphatic C a would sufficiently reveal the generality of this interaction for any non-p* acceptors. On the other hand, different carbamates and esters account for the generality of carbonyl substituent effects.
The 13 C NMR signals (Table 1) of C a in homologous alcohols 28,29 undergo a large downeld shi (by 18.7 ppm) incrementally as the number of methyl (C b H 3 ) substituents on C a increases from zero to three (Fig. 2a). There is a simultaneous downeld shi in the 1 H NMR signal of the corresponding H a by 0.55 ppm from methyl to isopropyl alcohol. Such shis are contrary to what is expected from the increased positive induction on C a -H a by the C b H 3 substituents. They are rather due to the positive charge at C a stemming from the polarization of the C a -O bond, which is stabilized through the hyperconjugation effect (and increasingly so) as the number of methyl substituents on C a increases. Hence, the C a -C b s-bonds Table 1 Comparison of relevant 1 H NMR, 13 C NMR (CDCl 3 ) and FT-IR spectral data (CHCl 3 ) of pyrrolidine carbamates (1-4) N-phenyl carbamates (5-8), alkyl acetates (9-12), alkyl benzoates (13)(14)(15)(16) and their corresponding homologous alcohols (17-20) a  of alcohols have additional bonding from such hyperconjugative resonance (HCR).
In the corresponding carbamates (1-4, 5-8 (ref. [30][31][32]) and esters (9-12, 13-16 (ref. [33][34][35]), there are much larger downeld shis for C a (by 26.6 ppm for 1-4; 28.1 ppm for 5-8; 28.5 ppm for 9-12; and 29.4 ppm for [13][14][15][16] and H a (by 1.23 ppm for 1-3; 1.27 ppm for 5-7; 1.32 ppm 9-11; and 1.32 ppm 13-15) compared to that for alcohols 28,29 (Fig. 2a and b). These shis are also incremental on increasing the C b H 3 substitution on C a but show steeper increase compared to that for alcohols (see ESI †). This further substantiates the hyperconjugative stabilization of greater positive polarization at C a of C a -O-C]O, whose oxygen exists as an oxonium ion in the bipolar resonance form (C a -O + ] C-O À ) (Fig. 3). Note that if merely the electron-withdrawing induction effect of the carbonyl group was inuencing the chemical shis of C a and H a , a constant downeld shi would have been observed on increasing the C b H 3 substitution at C a in either carbamates and esters compared to that for alcohols and not such incremental (steeper) downeld shis.
The remarkable uniformity in the trends of such increments in the C a and H a chemical shis for the R-O-C(R 0 )]O groups (R 0 represents primary and secondary amine, R stands for alkyl and aryl groups) of 1-16 reveals that this stabilization of the bipolar R-O + ]C(R 0 )-O À intermediates by the hyperconjugative effect from the R group is largely independent of the acyl substituent (R 0 ) effects and is only slightly perturbed by the cross-conjugation from the nitrogen in R 0 .  [42][43][44][45][46] of the homologous alcohols in the solid state (ESI †), which are re-ected in their stretching frequencies (1697 AE 8 cm À1 , 1679 AE 3 cm À1 , 1740.5 AE 7.5 cm À1 and 1723 AE 7 cm À1 , respectively) in the FT-IR spectra, 30,32,47-50 however, clearly indicate the additional electronic resonance along the N-C]O framework. As a result, the 13 C nuclear resonance for C]O in carbamates shis upeld compared to that for the esters. However, since the shi is constant and independent of the number of methyl substituents on C a , the mixing of nitrogen lone pair with the carbonyl p-cloud does not perturb the oxonium charge state or the concomitant positive charge at C a . The resonance at O-C]O is hence quite strong. The shortening of the O-C single bond in the carbamates and esters, noted from the diffraction data, evidences such strong resonance at O-C]O. In fact, the lowering of the rotational energy barrier along the C-N bond in carbamates than that in the corresponding amides by 3-4 kcal mol À1 , 13,14 indicates the overwhelming inuence of strong resonance at O-C]O in diminishing the resonance at N-C]O.
Interestingly, the FT-IR C]O stretching frequencies in the carbamates and esters consistently show an inverse correlation with the downeld shis at their alcohol C a (Fig. 2c and d), indicating interactive dependence between the negative charge at the carbonyl oxygen and the positive polarization at C a , an O/C a interaction that remarkably improves on increasing the number of C b H 3 substituents on C a .
Such The antiperiplanar orientation of C]O to the C a -C b bond in the carbamates and esters in the solid state and the O/C a interactions suggested by spectral indicators were consistent with each other. Interestingly, the C b signals in the 13 C NMR spectra of the carbamates and esters identically shied upeld on increasing the C b H 3 substitution at C a (Fig. 2e) compared to that for alcohols; this was in contrast to the C a signals, which shied down-eld. However, the H b signals in the 1 H NMR spectra showed downeld shis of decreasing steepness with decrease in the electronic charge at the carbonyl oxygen in the order alkyl benzoates > N-phenyl carbamate > acetates/ pyrrolidine carbamates (Fig. 2f). These indicate the predominance of the charge / HCR* (O/C a -C b ) interaction (Fig. 1c(i)) over the charge / s* (along C a -H a or C a -C b ) interaction and slightly greater electronic back donation of the charge from C]O to C a -C b in the acetates and pyrrolidine carbamates (Fig. 1c(ii)). There were consistent slight deviations in This journal is © The Royal Society of Chemistry 2020 RSC Adv., 2020, 10, 11871-11875 | 11873 particularly the d ppm values of H b for all the isopropyl carbamate and ester analogues (3,7,11,15), as observed from the trends obtained for the remaining homologues. This was consistent with the small distortions away from the ideal antiperiplanarity of the carbonyl oxygen and the C a -C b bond observed in their crystal structures, which diminished the charge / HCR* donation and would not be observed unless charge / HCR* predominated over charge / s* in O/C a .
The generic charge / acceptor O/C a electronic back donation interactions explain the X-ray structures of phenyl carbamates, 21 where the inclusive plane of the carbamate group is perpendicular to the plane of the phenyl ring. 22 Current data additionally indicate that this interaction is (a) largely charge / p* in nature rather than n / p*; (b) primarily localized between O and C a of the phenyl ring; and (c) a consequence of the general O/C a charge / acceptor electronic interactions at the R-O-C]O groups, which are observed for a variety of C a acceptors: (1) s* acceptor in C a -H a , when R is a methyl group (Fig. 1c(ii)); (2) HCR* acceptor in C a -C b , when R has a C b H group (Fig. 1c(i)); and (3) p* acceptor, when R is phenyl (Fig. 1b). In other words, the O/C a electronic charge / acceptor back donation interaction is observed at alkyl carbamates and esters as well as they are observed in phenyl carbamate.
Note that only a charge (rather than a lone pair) donor at the carbonyl oxygen, which has a longer coulombic interaction range, is consistent with the reported observations for phenyl carbamates 22 that the rest of the p*-orbitals of the phenyl ring (other than at its C a ) that are at distances longer than is conducive for any n / p* orbital overlap interactions also accept electron density from the carbonyl oxygen. Moreover, the constancy (rather than decrease) in the O/C a interactions despite increasing the substitution at C a and the concomitant upeld shi in the C b signals of the current analogues and the O/C a -C b periplanarities with little perturbation in the O/C a distances in crystals all substantiate an R group-dependent stabilization of the negative charge on the carbonyl oxygen, which interacts back with C a of R and inuences the rotational states of the O-C a bond at the R-O-C]O groups. Thus, the charge / acceptor O/C a interaction is generic to the C a -O-C]O group and inuences the biasing of the rotational states along the O-C a bond. The incorporation of the corresponding force elds in the computational methods will benet energy minimization of the rotational states in these molecules. The generic charge / HCR*/s*/p* interaction model at C a -O-C] O is also consistent with masking the charge at the carbonyl oxygen, hence explaining the low basicities and poor hydrogen bond acceptor propensities of the carbamates and esters.
Finally, it is possible that the O/C a interaction has an electrostatic component as well due to the polarized charge at C a . Although this may inuence the planarity of R-O-C]O even when R is a methyl group, the resonance at O-C]O would have a major role in such planarity. Moreover, such electrostatic interactions are insufficient by themselves to explain the observed C]O/C a -C b anti-periplanarities and the relative downeld shiing of H b (compared to alcohols). Note that the latter data also discount the possibility of O/H a -C a or O/H b -C b -type hydrogen bonding interactions.

Conclusions
Correlations between the 1 H NMR, 13 C NMR and FT-IR spectral data for the C a -O-C]O groups of the model carbamates and esters of homologous alcohols reveal the presence of charge / HCR*/s* donor/acceptor O/C a interactions along with other structural and electronic features, which explain several of the apparently anomalous properties of carbamates and esters. First, there is positive charge polarization at the C a carbon attached to the alcohol oxygen, which is stabilized incrementally by hyperconjugative resonance (HCR) with increasing number of C b H 3 substituents on it. Interestingly, the resulting dipolar resonance at O-C]O is comparable for carbamates and esters and is slightly perturbed by the cross-resonance from the (secondary and tertiary) carbamate nitrogen. Rather, the latter is weakened, explaining the lowering of the transition energy barrier for cis/trans isomerism at the carbamate C-N bonds compared to that for amides. The electronic charge at the carbonyl oxygen of carbamates and esters interacts back with the hyperconjugative resonance (HCR*) along C a -C b or with s* along C a -H a , as substantiated by the NMR and FT-IR spectral shis (compared to those for the corresponding alcohols). Such an interaction regulates the rotational states along the O-C a bonds, as seen from the C]O/C a -C b and C]O/C a -H a antiperiplanarities in the crystal structures of carbamates and esters. Deviations in the anti-periplanarities are directly re-ected through spectral shis. This charge / acceptor O/C a interaction thus occurs with any (HCR*, s* or p*) acceptor at C a and explains several unique features of the C a -O-C]O groups: (1) the unusual orthogonality observed between the planes of phenyl and carbamate groups in phenyl carbamates and (2) the diminished basicities and hydrogen bond accepting propensities of the carbamate and ester carbonyl oxygens compared to that for ketones and amides. This is the rst insight into the strong interdependence between the alcohol group and the charge at the carbonyl group of the C a -O-C]O groups of carbamates and esters, resulting in charge-stabilizing generic charge / acceptor O/C a interactions that bias the rotational states of the O-C a bond. Apart from providing a better understanding of the interactions in the R-O-C]O groups, the current results will help in chemical biology research 51 and drug design, [52][53][54] where carbamates play an important role.

Conflicts of interest
There are no conicts to declare.