The chemistry of N,N′-dimethylformamidine. II. Hydrolysis. Kinetically controlled formation of cis-N-methylformamide

Abstract

The hydrolysis of N,N′-dimethylformamidine (DMFA) has been investigated in acid and alkaline aqueous media by 1H nmr; only a narrow basic pH range could be extensively studied kinetically. The pseudo-first-order kobs rose steadily from pH 11.5 to 13.0 (reaction approximately first order in OH−), then became independent of pH above 13.5 (9.3 × 10−4 s−1 at 10 °C). In contrast to many amidines, DMFA is quite stable in acid solution (estimated value of the pseudo-first-order hydrolysis rate constant is 1.4 × 10−1 s−1 at 10 °C, pH 0.05, from measurements at 100 and 140 °C). This stability is ascribed to the difficulty of eliminating the fairly strong base methylamine from the tetrahedral intermediate in acid solution.N-Methylformamide (NMF), one of the products, is formed initially as the cis isomer. A somewhat slower conversion then occurs to the thermodynamically more stable trans isomer. This unusual result is explained in terms of Deslongchamps and co-workers' theory of stereoelectronic control for the orbital-assisted breakdown of tetrahedral intermediates.

Hydrolysis and Hydrogenolysis of Formamidines: N,N-Dimethyl and N,N-Dibenzyl Formamidines as Protective Groups for Primary Amines

“…Hydrolysis Reactions. The mechanism of amidine hydrolysis has been studied in detail elsewhere. ,− The reaction proceeds via the formation of a hemiorthoamide that can cleave in two different ways (Scheme ).

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The chemistry of N,N′-dimethylformamidine. I. Formation from potassium methylamide and its thermal stability

“…The results of an 1~ nmr study of tautomeric exchange in solutions more of the absorption band was visible DMFA and its solutions is reported in Part 111 of this series and both growth of the DMFA anion peak and loss (9), while its hydrolysis is discussed in Part 11 (7). of the methylamide ion peak could be seen (Fig.…”

“…However, con- firmation of the uv-visible analytical approach to measuring the thermolysis rate was obtained by nmr, utilizing the fact that DMFA is stable in aqueous acid solution at ambient temperature (7). For several thermolysis runs, 2 mL samples of PMA reaction solution were removed from the vessel each time a uv-visible spectrum was run.…”

Hydrolytic deamination reactions of amidine and nucleobase derivatives

“…As shown in Scheme 2, in the first step of the deamination reaction, tautomerization of the amine form (R) to the imine form (I 1 ) takes place by a water-mediated proton transfer from the amino nitrogen (N 7 ) to the N 3 via the resonance stabilized TS 1 (numbering of atoms can be seen in As can be seen in Table 1 (see also Figure 1 [10] Cyt (7) [38] 122 (121) 117 ± 4 [23] 1-mCyt (8) [38] 82 71 ± 13 [21] C< >U (16) [38] 94…”

“…This would suggest similar mechanisms are likely for the deamination reactions of all amidine and nucleobase derivatives. Also, nucleobases and their derivatives have the potential to exist in several keto−enol or imino−amino tautomeric forms, [1][2][3][4][5][7][8][9][10][11][12] and such tautomeric distribution has a major effect on deamination reactions of these molecules. The spontaneous deamination of nucleobases is a source of DNA mutations.…”