Chemistry

F. M. Stoyanovich, B. P. Fedorov, and G. M. Andrianova

Reactions of Amidomercaptals with Compounds Containing a Primary Amino Group

(Presented by Academician B. A. Kazanskii, May 3, 1962)

The \(N,N\)-dialkylamino-dialkylmercaptomethanes (I) obtained by us earlier \((^1)\) are thioacetals, or, in other words, mercaptals of \(N\)-substituted amides; by analogy with the amidoacetals recently discovered by Meerwein and co-workers \((^2,\,^3)\), we shall hereafter call them amidomercaptals. Amidomercaptals are distinguished by enhanced reactivity: they readily undergo hydrolysis and oxidation, react with alcohols, amines, amides, and organometallic compounds, and enter into other reactions.

The present communication gives syntheses of other representatives of this new class of organic compounds and reactions of amidomercaptals with compounds containing a primary amino group. Dimethylformamide diethyl mercaptal \((N,N\)-dimethylamino-diethylmercaptomethane) (Ia) was obtained in 44.7% yield by the reaction of ethyl mercaptan with dimethylformamide and phosphorus oxychloride. By the same method \((^1)\), from 1,2-ethanedithiol, a cyclic amidomercaptal was synthesized in 38.5% yield,

\[ (\mathrm{CH}_3)_2\mathrm{NCH} \]

* Analysis was performed for the picrate.
* \(n_D^{20}\) 1.5432.
** \(n_D^{20}\) 1.5842.

2-dimethylamino-1,3-dithiolane (Ib). In contrast to the acyclic compounds, amidomercaptal Ib is more stable and, on treatment with picric acid, does not decompose, but gives a picrate which, however, is readily converted into dimethylamine picrate on recrystallization from alcohol.

Amidomercaptals react without a catalyst, on heating to 110–175°, with various classes of organic substances containing a primary amino group, according to the following equation:

\[ (\mathrm{CH}_3)_2\mathrm{NCH} \begin{matrix} \diagup \mathrm{SR}\\[-2mm] \diagdown \mathrm{SR'} \end{matrix} +\mathrm{H}_2\mathrm{NR''} \rightarrow (\mathrm{CH}_3)_2\mathrm{NCH}=\mathrm{NR''}+\mathrm{RSH}+\mathrm{R'SH} \]

\[ \tag{I} \]

a) \( \mathrm{R}=\mathrm{R'}=-\mathrm{C}_2\mathrm{H}_5,\quad \)
b) \( \mathrm{R}+\mathrm{R'}=-\mathrm{CH}_2\mathrm{CH}_2-,\quad \)
c) \( \mathrm{R}=\mathrm{R'}=-n\text{-}\mathrm{C}_4\mathrm{H}_9 \)

The reaction proceeds equally readily with aliphatic, cycloaliphatic, araliphatic, and aromatic amines, and in all cases N,N-dimethyl-N′-alkyl(aryl)formamidines are obtained (II—V, see Table 1). The interaction of dimethylformamidomercaptal Ib with 2,4-dinitrophenylhydrazine leads to the corresponding formamidrazone (VI).

Similar transformations in the case of amidoacetals \(^{(2)}\) were observed by Meerwein and co-workers \(^{(3)}\). It was shown that amidoacetals at 80–140° react with aromatic amines, semicarbazide, and 2,4-dinitrophenylhydrazine with the formation of formamidines and formamidrazones. However, he did not study the interaction of amidoacetals with unsubstituted amides. It turned out that amidomercaptals also readily react with amides (for example, benzamide), sulfonamides (\(p\)-toluenesulfonamide), and other compounds containing an unsubstituted amino group, and in this way N-substituted acylformamidines can be synthesized (for example, VII—X, Table 1).

\[ =\mathrm{NR''} \]

Table 1

The structure of the compounds obtained was confirmed by elemental-analysis data, by comparison of their constants with constants reported in the literature (for known compounds), by preparation of derivatives (picrates), and also by infrared spectra. The spectra of the formamidines were recorded in chloroform. In the spectrum of N,N-dimethyl-N′-(β-hydroxyethyl)formamidine (II), in agreement with the proposed structure, an intense band at 1650 cm\(^{-1}\) is observed, which may be assigned to stretching vibrations of the C=N bond, and a diffuse band in the region 3500–3100 cm\(^{-1}\), due to stretching vibrations of associated OH groups. In the spectrum of N,N-dimethyl-N′-thiocarbamylformamidine (X), two intense absorption bands with frequencies of 1580 and 1630 cm\(^{-1}\) are observed in the region 1500–1700 cm\(^{-1}\); of these, the latter is apparently due to stretching vibrations of the C=N bond, and the former to deformation vibrations of the NH\(_2\) group. In the region of NH\(_2\) stretching vibrations, as in primary amines, two bands are observed, at 3390 and 3520 cm\(^{-1}\), corresponding to symmetric and antisymmetric vibrations of the NH\(_2\) group. Bands characteristic of the C=S bond are usually found in the region 1300–1400 cm\(^{-1}\). In the spectrum of compound X, in this region there is a series of bands of identical intensity; however, it is not possible to assign any one of them with certainty to vibrations of the C=S bond. Nevertheless, the presence of the C=N and NH\(_2\) bands confirms the structure assigned to X.

In the spectra of the remaining substituted formamidines (III–IX), frequencies have been found confirming the presence of stretching vibrations of the C=N bond, somewhat shifted owing to conjugation.

The reaction of amidomercaptals with compounds containing a primary amino group is a new method \(^{(4)}\) for obtaining substituted formamidines, which may be important in cases where the presence of other reactive groups, for example hydroxyl, does not permit the use of acidic catalysts required for the usually employed methods of synthesis \(^{(5-7)}\). By means of this reaction, formamidines can readily be obtained from amino compounds of important biological and pharmacological significance. For example, white streptocide forms bis-formamidine (IX):

\[ (\mathrm{CH}_3)_2\mathrm{NCH}=\mathrm{N}- \begin{matrix} \chemfig{*6(-=-(-\mathrm{SO_2N}=\mathrm{CH}-\mathrm{N}(\mathrm{CH}_3)_2)=-=)} \end{matrix} \]

\[ \text{(IX)} \]

The reaction conditions, yields, constants, and analyses of the formamidines obtained by this method are presented in Table 1.

Experimental Part

N,N-Dimethylformamidodiethylmercaptal (Ia). To a transparent mixture of 73 g (1 mole) of dimethylformamide and 124 g (2 moles) of ethyl mercaptan, 153.6 g (1 mole) of POCl\(_3\) was added at −3 to −5° with stirring. After being brought to room temperature over the course of two hours, the mass was kept for 45 h, then poured with stirring into an ice-cold solution of sodium carbonate; the oil that separated was extracted with ether and washed with NaCl solution. After drying with MgSO\(_4\), the ethereal extract was freed from solvent, and the residue was distilled in vacuo. 80.0 g of N,N-dimethylformamidodiethylmercaptal (Ia) was obtained, b.p. 110–113°/23 mm; 98–101°/13 mm, \(n_D^{20}\) 1.5108.

\[ \begin{aligned} &\text{Found \%: } &&\mathrm{C}\ 46.90,\ 47.14;\quad \mathrm{H}\ 9.43,\ 9.43;\quad \mathrm{S}\ 35.90,\ 35.72\\ &(\mathrm{CH}_3)_2\mathrm{NCH}(\mathrm{SC}_2\mathrm{H}_5)_2.\ \text{Calculated \%: } &&\mathrm{C}\ 46.87;\quad \mathrm{H}\ 9.55;\quad \mathrm{S}\ 35.75 \end{aligned} \]

2-Dimethylamino-1,3-dithiolane (Ib). To a mixture of 21.9 g (0.3 mole) of dimethylformamide and 28.2 g (0.3 mole) of 1,2-ethanedithiol was added dropwise over the course of an hour 46.1 g (0.3 mole) of POCl\(_3\), with stirring and cooling.

to 2–7°. After standing for three days at room temperature, the red, transparent, thick mass was poured into a mixture of 200 g of sodium bicarbonate and 400 ml of a 40% solution of ammonium sulfate and was repeatedly extracted with ether. The ethereal extracts, after washing with saturated NaCl solution, were dried over MgSO₄. After removal of the ether and distillation, 17.28 g (38.5%) of 2-dimethylamino-1,3-dithiolane (16) was obtained, b.p. 97–98.5°/10 mm; \(n_D^{20}\) 1.5678.

Found, %: C 40.36, 40.37; H 7.27, 7.42; S 42.83, 43.00
\( \mathrm{C_5H_{11}NS_2} \). Calculated, %: C 40.22; H 7.42; S 42.95

Picrate: m.p. 99.5–101° (from chloroform).

Found, %: C 34.94, 35.02; H 3.63, 3.79; S 16.94, 16.92
\( \mathrm{C_{11}H_{14}N_4O_7S_2} \). Calculated, %: C 34.91; H 3.73; S 16.94

General method for the preparation of formamidines. Equimolecular amounts of the primary amino compound and the amidomercaptal are heated at 110–175° for such a time as is sufficient for distillation of the mercaptan formed as a result of the reaction (usually 0.5–2 h). The residue is recrystallized or distilled, depending on the properties of the formamidine obtained, and sometimes the latter is isolated in the form of a picrate.

Institute of Organic Chemistry
named after N. D. Zelinsky
Academy of Sciences of the USSR

Received
25 IV 1962

REFERENCES

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