4712
J. Org. Chem. 1997, 62, 4712-4720
Nitrosation of Amines in Nonaqueous Solvents. 2. Solvent-Induced Mechanistic Changes L. Garcı´a-Rı´o,† J. R. Leis,*,† and E. Iglesias‡ Departamento de Quı´mica Fı´sica, Facultad de Quı´mica, Universidad de Santiago, 15706 Santiago de Compostela, Spain, and Departamento de Quı´mica Fundamental e Industrial, Facultad de Ciencias, Universidad de La Corun˜ a, La Corun˜ a, Spain Received February 3, 1997X
We studied the nitrosation of amines (pyrrolidine, piperidine, diethylamine, N-methylpiperazine, N,N ′-dimethylethylenediamine, and morpholine) by alkyl nitrites (2-bromoethyl nitrite or 2,2dichloroethyl nitrite) or by N-methyl-N-nitroso-p-toluenesulfonamide (MNTS) in the solvents chloroform, acetonitrile, and dimethyl sulfoxide (DMSO). The mechanism of nitrosation by alkyl nitrites depends on the solvent: in chloroform, all the results were in keeping with formation of a hydrogen-bonded complex between the amine and alkyl nitrite being followed by rate-controlling formation of a tetrahedral intermediate T( that rapidly decomposes to afford the final products; in acetonitrile, a situation intermediate between those obtaining in chloroform and cyclohexane results in the [amine] dependence of the first-order pseudoconstant k0 being qualitatively influenced by temperature and by the identities of both the amine and the alkyl nitrite; in DMSO, the results suggest a mechanism close to the mechanism acting in water. For nitrosation by MNTS, k0 depended linearly on [amine] in all three solvents. The Grunwald-Winstein coefficients correlating the rate constants k for nitrosation by MNTS in the chloroform, acetonitrile, DMSO, dioxane, dichloromethane, and water were l ) 0.12 and m ) 0.29. Correlation with the Kamlet-Abboud-Taft equation confirmed that k depends largely on the dipolarity of the solvent and, to a lesser extent, its capacity for hydrogen bonding. Introduction Studies of structure-reactivity relationships and solvent effects have widely popularized the idea that reaction mechanisms can be profoundly altered by changing reactant substituents and/or reaction medium.2 In the case of nucleophilic substitution and addition reactions, extensive application of this concept has allowed several new conclusions to be drawn with regard to the role of nucleophile, leaving group, and solvent in reaction mechanism. The classification of a series of solvents can present numerous difficulties.3 With this series of articles on nitroso group transfer, we set out to classify solvents phenomenologically by examining their effects on nitrosation kinetics. In part 11 we examined the reactions of several secondary amines with alkyl nitrites (RONO) and N-methyl-N-nitroso-p-toluenesulfonamide (MNTS) in nonaqueous apolar media (isooctane, cyclohexane, dichloromethane, 1,4-dioxane, and tetrahydrofuran) and found them to differ significantly from the corresponding aqueous phase reactions.4 We now report the extension of this study to the more polar nonaqueous solvents chloroform, acetonitrile, and dimethyl sulfoxide (DMSO), which were chosen in view of the results of part 1:1 acetonitrile and DMSO both have large dielectric constants ( ) 36 for acetonitrile, 45 for DMSO); DMSO in particular has a very high capacity †
Universidad de Santiago. Universidad de La Corun˜a. Abstract published in Advance ACS Abstracts, June 1, 1997. (1) Garcia-Rio, L.; Leis, J. R.; Iglesias, E. J. Org. Chem. 1997, 62, 4701. (2) (a) Jencks W. P. Chem. Rev. 1985, 6, 511. (b) Buncel, E.; Wilson, H. Adv. Phys. Org. Chem. 1977, 14, 133. (3) Reichardt, C. Solvents and Solvent Effects in Organic Chemistry; Verlag Chemie: Weinheim, 1986. (4) Garcia Rio, L.; Iglesias, E.; Leis, J. R.; Pen˜a, M. E.; Rios, A. J. Chem. Soc., Perkin Trans. 2 1993, 29. ‡
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S0022-3263(97)00189-8 CCC: $14.00
for solvation of ions; and proton donation by chloroform5 might affect HBC formation. We did not use alcohols (which would ideally have been desirable because of their structural similarity to water) because they are themselves readily nitrosated,6,7 and preliminary experiments in which nitrosation of formamides was detected similarly deterred us from further investigation of the nitrosation of amines in solvents of this family. As expected, we found that the more polar the solvent, the more strongly was the mechanism deduced for the reaction in cyclohexane distorted toward the mechanism acting in water. Of particular interest, however, was the finding that, for nitrosation by alkyl nitrites, acetonitrile represents a kind of singular point in the continuum of solvent properties, in that the mechanism acting in this solvent depends qualitatively on both the nature of the leaving group of the nitrosating agent and the nature of the amine (whereas in other solvents the identity of the amine generally has only a quantitative influence). This finding underlines the difficulty of classifying solvents or predicting their effects on even a single class of reaction3 and provides an elegant example of how the mechanism of a nucleophilic substitution reaction can depend critically on the nature of nucleophile, leaving group, and solvent.2
Experimental Section Chloroform (HPLC grade), acetonitrile (anhydrous), and DMSO (spectophotometric grade) were supplied by Aldrich and had nominal purities >99.9% and water contents MOR, and the sensitivity of the nitrosation reaction to the nature of the leaving group increases in the same order. Thus, for the least basic amine (MOR), the rate-controlling step can be either the formation or the decomposition of T(. The anomalous behavior of DEA, which also reacts with MNTS in water at a rate three times lower than that expected on the basis of its pKa, is attributable to the steric bulk of this amine impeding nucleophilic attack by it. For the reactions of the amines in DMSO the behavior observed was consistently similar to that in water, and the relative reactivities of piperidine, diethylamine, and morpholine with 2,2-dichloroethyl nitrite were evaluated as 24.6:6.2:1, which compare very well with those for nitrosation of these amines by MNTS in water (32:11.7: 1, respectively).4 Influence of Temperature. For the nitrosation of MOR and MePIP by 2,2-dichloroethyl nitrite in chloroform, the rate constants increased between 25 and 35 °C. However, for the corresponding reaction between PYR and 2-bromoethyl nitrite, the rate constant exhibited complex behavior that was indicative of regions of both positive and negative overall activation energy depending on the concentration of the amine. These results must be interpreted using true rate and equilibrium constants. From the data in Table 2, the effects of temperature on k2 (the rate of conversion of the HBC into products) and KC (the equilibrium constant for formation of the HBC) in eq 4 were evaluated: for the 10° rise in temperature, the k2 for nitrosation of PYR by 2-bromoethyl nitrite and for nitrosation of MePIP by 2,2-dichloroethyl nitrite increased by factors of 2.5 and 3.1, respectively (the results for nitrosation of MOR by 2,2-dichloroethyl nitrite were not considered indicative, since the corresponding plots of k0 against [amine] barely deviated from linearity), while KC decreased for all three amines, most notably in the case of PYR. The existence of regions of overall negative activacion energy was therefore attributed to the decrease in KC being greater than the increase in k2 (16) Johnson, S. L. Adv. Phys. Org. Chem. 1967, 5, 237.
Nitrosation of Amines in Nonaqueous Solvents
J. Org. Chem., Vol. 62, No. 14, 1997 4719
Table 9. Influence of Pyrrolidine and Isopropylamine or Water Concentration on the Pseudo-First-Order Rate Constant (k0) for Nitrosation of PYR by 2-Bromoethyl Nitrite in DMSO at 25 °C [PYR]/M
[iPrNH2]/M
k0/s-1
[PYR]/M
H2O/% vol
k0/s-1
3.7 × 10-2 7.33 × 10-2 0.15 0.30 0.41 0.59 0.74 0.31 0.31 0.31 0.31 0.31 0.31 0.31
0.16 0.16 0.16 0.16 0.16 0.16 0.16 2.33 × 10-2 4.67 × 10-2 9.34 × 10-2 0.19 0.37 0.75 0.93
2.21 × 10-4 5.75 × 10-4 1.08 × 10-3 2.09 × 10-3 2.81 × 10-3 3.93 × 10-3 4.72 × 10-3 2.02 × 10-3 2.03 × 10-3 1.98 × 10-3 2.01 × 10-3 1.99 × 10-3 2.05 × 10-3 2.00 × 10-3
7.01 × 10-2 7.01 × 10-2 7.01 × 10-2 7.01 × 10-2 7.01 × 10-2 7.01 × 10-2 7.01 × 10-2 7.01 × 10-2
6.67 × 10-2 0.13 0.27 0.53 1.07 2.13 3.53
4.56 × 10-4 4.61 × 10-4 4.63 × 10-4 4.65 × 10-4 4.57 × 10-4 4.76 × 10-4 4.96 × 10-4 5.90 × 10-4
Scheme 1 A. nitrosation of amines by alkyl nitrites RONO + R2NH
Kc
RONO•R2NH k2
RONO•R2NH
k–2
(HBC) O– R O N R N+ H R ± T
k4
ROH + R2NN O
k3 R2NH
ROH + R2NH + R2NN O B. nitrosation of amines by MNTS O Me
CH3
+ R2NH
S N O
N
O
O
k2
Me
CH3
S N
k–2
O
N O– N+ H R R
fast
O Me
CH3
S N O
+ R2NN O
H
for certain amine concentrations. Consistent with this interpretation are the effects of the temperature increase on k2 and the ratio k4/k3 (the ratio of the rate of spontaneous to base-catalyzed decomposition) for the nitrosation of DEA and MOR by 2,2-dichloroethyl nitrite in acetonitrile, which were evaluated from Table 3 and eq 3 as b/d and a/b, respectively. Specifically, k2 increases with temperature for both reactions (i.e., Arrhenius behavior) and so does the ratio k4/k3, thus indicating that spontaneous decomposition is favored at the higher temperature. The change in the rate-controlling step of PYR nitrosation by 2-bromoethyl nitrite in acetonitrile upon increasing the reaction temperature was rather surprising. For reaction at 25 °C and amine concentrations
