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Ab initio investigations of the hydrolysis of the carbamate bond
Journal of Molecular Structure (Theochem), 204 (1990) 331-335 Elsevier Science Publishers B.V., Amsterdam - Printed in The Netherlands
331
AB INITIO INVESTIGATIONS OF THE HYDROLYSIS OF THE CARBAMATE BOND
MILAN REMKO Department of Pharmaceutical Chemistry Comenius University, 832 32 Bratislava (Czechoslovakia) STEVE SCHEINER Department of Chemistry and Biochemistry, Southern Illinois University, Carbondale, IL 62901 (U.S.A.) (Received 1 March 1989)
ABSTRACT The energies for model gas-phase decomposition and hydrolysis reactions of carbamic acid and methyl carbamate have been calculated at various levels of theory. The calculations indicate that esterification accelerates cleavage of the carbamate bond.
INTRODUCTION
Many carbamic acid esters are used as drugs [ 11. The geometry, internal rotational barriers, hydrogen bonds, and proton affinities of carbamic acid and several derivatives, calculated using various ab initio techniques, have been reported in previous articles [ 2-51. Ruelle et al. [ 61 studied the decarboxylation of carbamic acid with the STO-3G and 3-21G ab initio methods and recently the acid hydrolysis of methyl carbamate has been studied [ 71 using the MNDO method. In the present study the decomposition of carbamates was investigated. Special attention was devoted to the acid hydrolysis of the carbamate bond in carbamic acid and methyl carbamate. COMPUTATIONAL
DETAILS
The geometry of carbamic acid, methyl carbamate, and their decomposition and hydrolysis products were completely optimized using the gradient-optimization method [8] and the 3-21G [9] and 6-31G* [lo] basis sets. The effect of electron correlation on the computed reaction energies was investigated by means of second- and third-order Meller-Plesset (MP2, MP3) perturbation
332
theory in connection with the 6-31G* basis set. The equilibrium geometries of carbamic acid and methyl carbamate and some protonated species have been published elsewhere [ 2,4]. The precise geometry specification used in this study may be obtained from the authors. All calculations were performed using the GAUSSIAN 80 program [ 111. RESULTS AND DISCUSSION
Carbamic acid is an unstable compound and under laboratory conditions undergoes decarboxylation to give CO2 and NH,. The results of the ab initio studies of the vapor-phase decomposition of carbamic acid and methyl carbamate in the model reaction NH,-COOR+NH,R+CO,
(1)
R= H, CH, are reported in Table 1. The reaction energy, dE, was computed as the difference between the total energies of the reaction products and the reactants, and depends upon the basis set used. The small 3-21G basis predicts this reaction to be endothermic at the SCF level. Including the effect of electron correlation (MP2) brings additional stabilization to the reaction products and reverses the sign of the reaction energy. A substantially negative reaction energy was, however, calculated using the larger 6-31G* basis set even at the SCF level. The correlation effect computed at the MP2 level brought about further considerable energy decrease (about 530 kJ mol-‘). Extension of the correlation treatment to third-order MP was carried out in the case of carbamic acid cleavage, yielding a considerably smaller correction (about 15 kJ mol-’ ) to the MP2 reaction energy (Table 1) . The effect of esterification on the decomposition rate of the carbamate group was studied by comparison with methyl carbamate. In general, the more negative reaction energies computed for the cleavage of the N-C bond in this comTABLE 1 Reaction energies (dE) for the elimination of CO2 from NH,COOR [reaction (1) ] R
AE (kJ mol-‘) 3-21G
H CH,
6-31G*
SCF
MP2
SCF
MP2
MP3
50.9 64.9
-4.4 -9.0
- 289.1 -331.5
- 820.8 -963.7
- 836.2
333
pound (Table 1) indicate that esterification accelerates the decarboxylation of the carbamate moiety. In experimental practice, the decomposition reactions proceed in aqueous solution. Table 2 shows the calculated energy differences for this non-catalyzed hydrolysis reaction NH,-COOR+H,O+NH,
+CO, +ROH
(2a)
R=H, CH, The 3-21G basis-set calculations indicate that this reaction, like the decomposition, is endothermic. The values of AE computed for the carbamic acid are the same as for reaction (1). The decarboxylation of methyl carbamate may proceed in two steps. The first step is the hydrolysis of ester NH,-COOCH,+H,O+NH,COOH+CH,OH
(2b)
The highly unstable carbamic acid immediately decomposes to carbon dioxide and ammonia NH,COOH+NH,
+CO,
(2c)
The energy of reaction (2b) was calculated as 1.0 kJ mol-‘, -49.6 kJ mol-’ and-142.2 kJ mol-’ with SCF/3-21G, SCF/6-31G* and MP2/6-31G*, respectively. By adding these values to the corresponding AE of the carbamic acid decomposition in the first line of Table 1 [equivalent to dE for reaction (2~) ] the hydrolysis energies for the methyl carbamate [reaction (2a) ] are obtained. The slight differences in the corresponding calculated values for the decarboxylation of the methyl carbamate [reaction (1) ] and the hydration reaction (2a) indicate that dE for both reactions are practically equal (Tables 1 and2). For practical purposes the hydrolysis is realized in highly acidic or alkaline medium. Both acid [ 12-141 and alkaline hydrolysis [ 15,161 of carbamic acid esters have been studied experimentally. The first step in the mechanism of the acid hydrolysis of carbamates is the protonation of basic oxygen and nitroTABLE 2 Reaction energies (dE) for the hydrolysis of NH,COOR [reaction (2a) ] R
H CH3
AE (kJ mol-‘) 3-21G
6-31G*
SCF
SCF
MP2
MP3
50.9 51.9
-289.1 - 338.1
- 820.8 -963.0
- 836.2 -
334 TABLE 3 Reaction energies (dE) for the acid hydrolysis of NH,COOR calculated using the 6-31G* basis set Eqn.
R
H
3a 3b 3a 3b
CH,
dE (kJ mol-‘) SCF
MP2
MP3
-633.6 -354.3 -588.0 - 370.4
- 1068.5 - 908.6 - 1178.8 -1021.1
- 1092.1 -909.9
gen atoms. Because the MNDO calculations on the methyl carbamate protonation [ 171 show that the methoxy O*protonated form is the least stable, only the protonation of the carbonyl oxygen and nitrogen atoms were considered in the present study. The energy changes computed for the reaction NH,+-COOR+H,O+NH,+
+CO, +ROH
I NH,-COH+OR+H,O+NH,+ II
(3a)
+CO, +ROH (3b)
R=H, CH, are listed in Table 3. The reaction energies computed at the MP2 level are substantially lower than the corresponding Hartree-Fock values. The thirdorder contribution (MP3) has only a small effect on the reaction energy of the carbamic acid. Previous ab initio calculations [ 4 ] have shown that the protonated species II are more stable. Hence, for both compounds the calculated reaction energies are substantially more exoergic for reaction (3a). The results of the MP2/631G* calculations for both the carbamic acid and its methyl ester show (Table 3) that esterification leads to a more negative LIE for the acid hydrolysis of carbamic acid. Comparison of the corresponding values in Tables 2 and 3 shows that the hydrolysis catalyzed by the H+ ions [ eqn. (3) ] is energetically more favorable than the non-catalyzed hydrolysis [eqn. (2a) 1. However, these conclusions are based on calculations corresponding to the vapor state and zero temperature, and do not include some important factors such as the influence of environment and the effect of temperature, which may also play an essential role. ACKNOWLEDGMENT
This work was supported by a grant from the National Institutes of Health (GM29391 ).
335 REFERENCES M.E. Wolf (Ed.), Burger’s Medicinal Chemistry, 4th edn., Parts II and III, The Basis of Medicinal Chemistry, Wiley, New York, 1979, 1981. M. Remko and S. Scheiner, J. Mol. Struct. (Theochem), 180 (1988) 175. M. Remko and S. Scheiner, J. Mol. Struct. (Theochem), 181 (1988) 19. M. Remko, Coll. Czech. Chem. Commun., 53 (1988) 1141. M. Remko, Z. Phys. Chem., Leipzig, in press. P. Ruelle, U.W. Kesselring and H. Nam-Tran, J. Mol. Struct. (Theochem), 124 (1985) 41. I. Lee, Ch.K. Kim and BCh. Lee, J. Comput. Chem., 8 (1987) 794. 8 P. Pulay, Mol. Phys., 17 (1969) 197. 9 J.S. Binkley, J.A. Pople and W.J. Hehre, J. Am. Chem. Sot., 102 (1980) 939. 10 P.C. Hariharan and J.A. Pople, Theor. Chim. Acta, 28 (1973) 213. 11 J.S. Binkley, R.A. Whiteside, R. Krishnan, R. Seeger, D.J. DeFrees, H.B. Schlegel, S. Topiol, L.R. Kahn and J.A. Pople, QCPE, 13 (1981) 406. 12 V.C. Armstrong and R.B. Moodie, J. Chem. Sot. B, (1968) 275. 13 G.A. Olah and M. Calin, J. Am. Chem. Sot., 90 (1968) 401. 14 J. Berner, Z. Chem., 22 (1982) 221. 15 I. Christenson, Acta Chem. Stand., 18 (1964) 904. 16 M. Stankovicova, J. Cizmarik and M. Pesak, Pharmazie, 36 (1981) 810. 17 I. Lee, Ch.K. Kim and H.S. Seo, Bull. Korean Chem. Sot., 7 (1986) 395.
331
AB INITIO INVESTIGATIONS OF THE HYDROLYSIS OF THE CARBAMATE BOND
MILAN REMKO Department of Pharmaceutical Chemistry Comenius University, 832 32 Bratislava (Czechoslovakia) STEVE SCHEINER Department of Chemistry and Biochemistry, Southern Illinois University, Carbondale, IL 62901 (U.S.A.) (Received 1 March 1989)
ABSTRACT The energies for model gas-phase decomposition and hydrolysis reactions of carbamic acid and methyl carbamate have been calculated at various levels of theory. The calculations indicate that esterification accelerates cleavage of the carbamate bond.
INTRODUCTION
Many carbamic acid esters are used as drugs [ 11. The geometry, internal rotational barriers, hydrogen bonds, and proton affinities of carbamic acid and several derivatives, calculated using various ab initio techniques, have been reported in previous articles [ 2-51. Ruelle et al. [ 61 studied the decarboxylation of carbamic acid with the STO-3G and 3-21G ab initio methods and recently the acid hydrolysis of methyl carbamate has been studied [ 71 using the MNDO method. In the present study the decomposition of carbamates was investigated. Special attention was devoted to the acid hydrolysis of the carbamate bond in carbamic acid and methyl carbamate. COMPUTATIONAL
DETAILS
The geometry of carbamic acid, methyl carbamate, and their decomposition and hydrolysis products were completely optimized using the gradient-optimization method [8] and the 3-21G [9] and 6-31G* [lo] basis sets. The effect of electron correlation on the computed reaction energies was investigated by means of second- and third-order Meller-Plesset (MP2, MP3) perturbation
332
theory in connection with the 6-31G* basis set. The equilibrium geometries of carbamic acid and methyl carbamate and some protonated species have been published elsewhere [ 2,4]. The precise geometry specification used in this study may be obtained from the authors. All calculations were performed using the GAUSSIAN 80 program [ 111. RESULTS AND DISCUSSION
Carbamic acid is an unstable compound and under laboratory conditions undergoes decarboxylation to give CO2 and NH,. The results of the ab initio studies of the vapor-phase decomposition of carbamic acid and methyl carbamate in the model reaction NH,-COOR+NH,R+CO,
(1)
R= H, CH, are reported in Table 1. The reaction energy, dE, was computed as the difference between the total energies of the reaction products and the reactants, and depends upon the basis set used. The small 3-21G basis predicts this reaction to be endothermic at the SCF level. Including the effect of electron correlation (MP2) brings additional stabilization to the reaction products and reverses the sign of the reaction energy. A substantially negative reaction energy was, however, calculated using the larger 6-31G* basis set even at the SCF level. The correlation effect computed at the MP2 level brought about further considerable energy decrease (about 530 kJ mol-‘). Extension of the correlation treatment to third-order MP was carried out in the case of carbamic acid cleavage, yielding a considerably smaller correction (about 15 kJ mol-’ ) to the MP2 reaction energy (Table 1) . The effect of esterification on the decomposition rate of the carbamate group was studied by comparison with methyl carbamate. In general, the more negative reaction energies computed for the cleavage of the N-C bond in this comTABLE 1 Reaction energies (dE) for the elimination of CO2 from NH,COOR [reaction (1) ] R
AE (kJ mol-‘) 3-21G
H CH,
6-31G*
SCF
MP2
SCF
MP2
MP3
50.9 64.9
-4.4 -9.0
- 289.1 -331.5
- 820.8 -963.7
- 836.2
333
pound (Table 1) indicate that esterification accelerates the decarboxylation of the carbamate moiety. In experimental practice, the decomposition reactions proceed in aqueous solution. Table 2 shows the calculated energy differences for this non-catalyzed hydrolysis reaction NH,-COOR+H,O+NH,
+CO, +ROH
(2a)
R=H, CH, The 3-21G basis-set calculations indicate that this reaction, like the decomposition, is endothermic. The values of AE computed for the carbamic acid are the same as for reaction (1). The decarboxylation of methyl carbamate may proceed in two steps. The first step is the hydrolysis of ester NH,-COOCH,+H,O+NH,COOH+CH,OH
(2b)
The highly unstable carbamic acid immediately decomposes to carbon dioxide and ammonia NH,COOH+NH,
+CO,
(2c)
The energy of reaction (2b) was calculated as 1.0 kJ mol-‘, -49.6 kJ mol-’ and-142.2 kJ mol-’ with SCF/3-21G, SCF/6-31G* and MP2/6-31G*, respectively. By adding these values to the corresponding AE of the carbamic acid decomposition in the first line of Table 1 [equivalent to dE for reaction (2~) ] the hydrolysis energies for the methyl carbamate [reaction (2a) ] are obtained. The slight differences in the corresponding calculated values for the decarboxylation of the methyl carbamate [reaction (1) ] and the hydration reaction (2a) indicate that dE for both reactions are practically equal (Tables 1 and2). For practical purposes the hydrolysis is realized in highly acidic or alkaline medium. Both acid [ 12-141 and alkaline hydrolysis [ 15,161 of carbamic acid esters have been studied experimentally. The first step in the mechanism of the acid hydrolysis of carbamates is the protonation of basic oxygen and nitroTABLE 2 Reaction energies (dE) for the hydrolysis of NH,COOR [reaction (2a) ] R
H CH3
AE (kJ mol-‘) 3-21G
6-31G*
SCF
SCF
MP2
MP3
50.9 51.9
-289.1 - 338.1
- 820.8 -963.0
- 836.2 -
334 TABLE 3 Reaction energies (dE) for the acid hydrolysis of NH,COOR calculated using the 6-31G* basis set Eqn.
R
H
3a 3b 3a 3b
CH,
dE (kJ mol-‘) SCF
MP2
MP3
-633.6 -354.3 -588.0 - 370.4
- 1068.5 - 908.6 - 1178.8 -1021.1
- 1092.1 -909.9
gen atoms. Because the MNDO calculations on the methyl carbamate protonation [ 171 show that the methoxy O*protonated form is the least stable, only the protonation of the carbonyl oxygen and nitrogen atoms were considered in the present study. The energy changes computed for the reaction NH,+-COOR+H,O+NH,+
+CO, +ROH
I NH,-COH+OR+H,O+NH,+ II
(3a)
+CO, +ROH (3b)
R=H, CH, are listed in Table 3. The reaction energies computed at the MP2 level are substantially lower than the corresponding Hartree-Fock values. The thirdorder contribution (MP3) has only a small effect on the reaction energy of the carbamic acid. Previous ab initio calculations [ 4 ] have shown that the protonated species II are more stable. Hence, for both compounds the calculated reaction energies are substantially more exoergic for reaction (3a). The results of the MP2/631G* calculations for both the carbamic acid and its methyl ester show (Table 3) that esterification leads to a more negative LIE for the acid hydrolysis of carbamic acid. Comparison of the corresponding values in Tables 2 and 3 shows that the hydrolysis catalyzed by the H+ ions [ eqn. (3) ] is energetically more favorable than the non-catalyzed hydrolysis [eqn. (2a) 1. However, these conclusions are based on calculations corresponding to the vapor state and zero temperature, and do not include some important factors such as the influence of environment and the effect of temperature, which may also play an essential role. ACKNOWLEDGMENT
This work was supported by a grant from the National Institutes of Health (GM29391 ).
335 REFERENCES M.E. Wolf (Ed.), Burger’s Medicinal Chemistry, 4th edn., Parts II and III, The Basis of Medicinal Chemistry, Wiley, New York, 1979, 1981. M. Remko and S. Scheiner, J. Mol. Struct. (Theochem), 180 (1988) 175. M. Remko and S. Scheiner, J. Mol. Struct. (Theochem), 181 (1988) 19. M. Remko, Coll. Czech. Chem. Commun., 53 (1988) 1141. M. Remko, Z. Phys. Chem., Leipzig, in press. P. Ruelle, U.W. Kesselring and H. Nam-Tran, J. Mol. Struct. (Theochem), 124 (1985) 41. I. Lee, Ch.K. Kim and BCh. Lee, J. Comput. Chem., 8 (1987) 794. 8 P. Pulay, Mol. Phys., 17 (1969) 197. 9 J.S. Binkley, J.A. Pople and W.J. Hehre, J. Am. Chem. Sot., 102 (1980) 939. 10 P.C. Hariharan and J.A. Pople, Theor. Chim. Acta, 28 (1973) 213. 11 J.S. Binkley, R.A. Whiteside, R. Krishnan, R. Seeger, D.J. DeFrees, H.B. Schlegel, S. Topiol, L.R. Kahn and J.A. Pople, QCPE, 13 (1981) 406. 12 V.C. Armstrong and R.B. Moodie, J. Chem. Sot. B, (1968) 275. 13 G.A. Olah and M. Calin, J. Am. Chem. Sot., 90 (1968) 401. 14 J. Berner, Z. Chem., 22 (1982) 221. 15 I. Christenson, Acta Chem. Stand., 18 (1964) 904. 16 M. Stankovicova, J. Cizmarik and M. Pesak, Pharmazie, 36 (1981) 810. 17 I. Lee, Ch.K. Kim and H.S. Seo, Bull. Korean Chem. Sot., 7 (1986) 395.