N. N. SVESHNIKOV, I. I. LEVKOEV, N. I. SHIROKOVA, N. A. DAMIR

THE ACTION OF PHOSGENE ON ACYLMETHYLENE DERIVATIVES OF HETEROCYCLIC BASES AND SOME REACTIONS OF THE COMPOUNDS FORMED THEREBY

(Presented by Academician M. I. Kabachnik, 3 VII 1962)

Acylmethylene derivatives of N-substituted heterocyclic bases, owing to the presence in them of a system of conjugated bonds between the tertiary nitrogen atom and the carbonyl oxygen, readily enter into electrophilic-addition reactions. Thus, under the action of alkylating agents they form quaternary salts of 2-β-alkoxyalkenyl derivatives of the corresponding bases (¹, ²). 2-Acylmethylene-3-alkylbenzthiazolines and -selenazolines react already at ordinary temperature with phosphorus oxychloride (³–⁵) or phosphorus oxybromide (³), giving salt-like products to which the structure of chloro- (or bromo-) alkylates of 2-β-chloro-(or bromo-) alkenylbenzthiazoles or -selenazoles (³–⁵) is assigned. It could be assumed that acylmethylene derivatives of N-substituted heterocyclic bases would react analogously with carbonic-acid chloranhydrides.

In the present work we have investigated the interaction of these compounds with phosgene. When a solution of 2-acetylmethylene-3-ethylbenzthiazoline (I) (0.44 g) in chloroform (10 ml) was added to a solution of phosgene (0.5 g) in the same solvent (6 ml), cooled to 0–5°, warming was observed and a colorless precipitate separated, which after 1.5–2 hours passed into solution with simultaneous evolution of carbon dioxide. After removal of the solvent in vacuo and washing of the residue with acetone, a colorless crystalline substance was obtained with m.p. 156–157°, sufficiently stable in air; this substance proved to be 2-β-chloropropenylbenzthiazole chloroethylate (II). (Found, %: Cl 25.61. C₁₂H₁₃NSCl₂. Calculated, %: Cl 25.86.) The yield was 97% of theoretical.

By addition of sodium iodide or perchlorate to an aqueous or methanolic solution of this salt, the corresponding iodide (m.p. 197–198°. Found, %: I 34.64; 34.99. C₁₂H₁₃NSClI. Calculated, %: I 34.71) and perchlorate (m.p. 194–195°. Found, %: Cl 20.91; 21.12. C₁₂H₁₃O₄NCl₂. Calculated, %: Cl 20.97) were obtained.

The reaction described evidently proceeds according to the scheme:

\[ \begin{gathered} \text{(I)}\quad \includegraphics[height=0pt]{} \end{gathered} \]

\[ \text{2-acetylmethylene-3-ethylbenzthiazoline} \ \xrightarrow{\ \mathrm{COCl_2}\ }\ \text{quaternary chloroformate intermediate} \ \longrightarrow\ \text{2-}\beta\text{-chloropropenylbenzthiazole chloroethylate (II)} + \mathrm{CO_2} \]

The quaternary salt (II) obtained differs from the product described by Bruker (³, ⁴) from the interaction of I with phosphorus oxychloride, which, as it proved, has no constant composition, is hygroscopic, and contains phosphorus (7.5–8.7%), apparently in the anion.

Further investigation showed that other 2-acylmethylene-N-alkylbenzthiazolines, -thiazolines, -benzselenazolines, -3,3-dimethylindolines, and -dihydroquinolines (⁶) react analogously with phosgene. By this method there were obtained in high yields, for example, 2-β-chloropropenylbenzselenazole chloroethylate (yield 90%, colorless needles, m.p. 153–154°. Found, %: Cl 22.08; 21.89. C₁₂H₁₃O₄NSeCl₂. Calculated, %: Cl 22.12) and ethyl perchlorate of 2-β-chlorostyrylquinoline (76%, yellowish crystals with

m.p. 160–161°. Found, %: Cl 18.14; 17.93. C\(_{19}\)H\(_{17}\)O\(_4\)NCl\(_2\). Calculated, %: Cl 17.99).

Quaternary salts of 2-β-chlorovinyl derivatives proved more conveniently prepared in benzene or toluene solution; moreover, they immediately separate from the reaction mixture in the crystalline state. In this way, for example, the chloroethylate was synthesized, and from it the more stable ethyl perchlorates of 2-β-chlorovinylbenzthiazole (yield 88%, pink crystals, m.p. 128–130°). Found, %: Cl 21.86, 21.79. C\(_{11}\)H\(_{11}\)O\(_4\)NSCl\(_2\). Calculated, %: Cl 21.87.

The vinylene homologs of 2-acylmethylene derivatives of heterocyclic bases react analogously with phosgene. Thus, from 2-formylallylidene-3-ethylbenzthiazoline there was obtained the ethyl iodide of 2-δ-chlorobutadienylbenzthiazole (yellow crystals, m.p. 169–170°). Found, %: I 33.49. C\(_{13}\)H\(_{13}\)NSClI. Calculated, %: I 33.61), and from the corresponding 2-acetylallylidene derivative—the chloroethylate of 2-δ-chloropentadienylbenzthiazole.

The reaction studied is analogous to those occurring under the action of phosgene on dimethylformamide, other disubstituted amides of carboxylic acids, and their vinylene homologs, for example, β-dimethylaminoacrolein (\(^{7-9}\)).

However, in comparison with the simplest dialkyl- or alkylaryl-α-chloroalkylideneammonium chlorides (\(^{7-9}\)), the quaternary salts of 2-β-chloroalkenyl derivatives of heterocyclic bases are considerably more stable. They dissolve without decomposition in cold water, forming neutral solutions to Congo; most of them change only slowly in air, becoming pink or greenish in color (exceptions are chloroalkylates of indolenine derivatives, as well as some 2-β-chlorovinylbenzthiazoles, which are hygroscopic and darken rapidly).

However, the chlorine atom in the β-position of the polymethine chain of the quaternary salts (III) is very mobile. These salts are rapidly hydrolyzed on heating with dilute hydrochloric acid, with formation of hydrochlorides of acylmethylene derivatives of the bases (IV). On boiling their alcoholic solutions or on heating with phenol at 160° (in greater yield under the action of potassium phenolate in phenol at 90–100°), the chlorine atom in these compounds is replaced, respectively, by an ethoxy or phenoxy group (V and VI). Thus, from salt II there were thereby obtained ethyl perchlorate of 2-β-ethoxypropenylbenzthiazole (m.p. 210–212°. Found, %: Cl 10.14, 10.24. C\(_{14}\)H\(_{18}\)O\(_5\)NSCl. Calculated, %: Cl 10.19) and ethyl iodide of 2-β-phenoxypropenylbenzthiazole, m.p. 180–182° (\(^{10}\)).

\[ \begin{array}{c} \text{(reaction scheme)}\\[2mm] \begin{array}{ccccc} & & \begin{array}{c} \includegraphics[width=0pt]{} \end{array} & & \\ & & \begin{matrix} \text{heterocyclic }N^+\text{ salt: } \\ \mathrm{Y}\text{-ring}-\mathrm{CH{=}C(R'){-}Cl}\\ \mathrm{R}\ \ \ \mathrm{Cl^-} \end{matrix} \ (III) & & \\[2mm] \mathrm{C_2H_5OH}\swarrow & & \downarrow\begin{matrix}\mathrm{NaSH}\\ \mathrm{Na_2S}\\ \mathrm{Na_2S_2O_3}\end{matrix} & & \searrow \mathrm{H_2O,\ HCl}\\[1mm] \begin{matrix} \mathrm{Y}\text{-ring}-\mathrm{CH{=}C(R'){-}OC_2H_5}\\ \mathrm{R}\ \ \ \mathrm{Cl^-} \end{matrix} \ (V) & & \begin{matrix} \mathrm{Y}\text{-ring}{=}\mathrm{CH{-}C(R'){=}S}\\ \mathrm{R} \end{matrix} \ (VIII) & & \begin{matrix} \mathrm{Y}\text{-ring}-\mathrm{CH{=}C(R'){-}OH}\\ \mathrm{R}\ \ \ \mathrm{Cl^-} \end{matrix} \ (IV) \\[3mm] \mathrm{C_6H_5OH}\swarrow & & & & \searrow \begin{matrix}\mathrm{R''}\\[-1mm]\mathrm{R'''}\end{matrix}\mathrm{NH}\\[1mm] \begin{matrix} \mathrm{Y}\text{-ring}-\mathrm{CH{=}C(R'){-}OC_6H_5}\\ \mathrm{R}\ \ \ \mathrm{Cl^-} \end{matrix} \ (VI) & & & & \begin{matrix} \mathrm{Y}\text{-ring}-\mathrm{CH{=}C(R'){-}N(R'')(R''')}\\ \mathrm{R}\ \ \ \mathrm{Cl^-} \end{matrix} \ (VII) \end{array} \end{array} \]

\(Y = S,\ Se,\ C(CH_3)_2,\ CH=CH;\quad R =\) alkyl, \(R' = H,\) alkyl or aryl;
\(R'' =\) alkyl or aryl; \(R''' = H\) or alkyl.

With aliphatic and aromatic primary and secondary amines, in alcoholic solution the salts (III), already at ordinary temperature, form hemicyanine dyes (VII) in high yields; under the action of hydrosulfides, sulfides, or thiosulfates of alkali metals they are converted almost quantitatively into thioacylmethylene derivatives of bases (VIII) \((^{11})\). Thus, when aniline (0.93 g) was introduced into an alcoholic solution of salt II (1.6 g in 20 ml) and, after 10 min, a 10% potassium iodide solution (50 ml) was added, the iodethylate of 2-β-anilinopropenylbenzothiazole was obtained. Yield 92%, yellow prisms with m.p. 210–211° \((208^\circ\ (^{12}), 210–211^\circ\ (^{13}))\). Similarly, from this salt there were synthesized, for example, the iodethylate of 2-β-piperidylpropenylbenzothiazole (yield 80%, pink prisms with m.p. 237–239°. Found, %: J 30.60. \(C_{17}H_{23}N_2SJ\). Calculated, %: J 30.65), the methyl perchlorates of 2-β-phenylaminostyryl (84.5%, bright-yellow prisms with m.p. 182–183° \((^{14})\)) and 2-β-N-tetrahydroquinolylstyryl-3,3-dimethylindolenine (65%, orange needles with m.p. 197–198°).

To obtain 2-thioacetylmethylene-3-ethylbenzothiazoline, an aqueous solution of sodium hydrosulfide or thiosulfate (0.42 g in 1.0 ml or 2.5 g in 2.5 ml) was added to a methanolic solution of salt (II) (1.4 g in 10 ml), whereupon a yellow crystalline precipitate rapidly separated. Yields 86.5 and 92%, m.p. 145–146° \((142–144^\circ\ (^{4}))\). Similarly, there were synthesized, for example, 2-thiobenzoylmethylene-3-ethylbenzothiazoline (93.5%) with m.p. 192–193° \((194–196^\circ\ (^{15}))\), 2-thiopropionylmethylene-3-ethyl-5,6-dimethylbenzothiazoline (100%) with m.p. 158–159° \((164–167^\circ\ (^{16}))\), and 2-thiobenzoylmethylene-1,3,3-trimethylindoline (96%, red needles with m.p. 137–138°).

Further experiments showed that salts (III) and their vinyl homologs in alcoholic solution, in the presence of triethylamine, already at ordinary temperature readily enter into a condensation reaction with quaternary salts of various heterocyclic bases containing an active methyl group, and also with ketomethylene compounds, with formation respectively of carbo-, dicarbo-, and polymethinemerocyanines:

\[ \begin{array}{c} \text{[[visible chemical reaction scheme: quaternary heterocyclic chloroethylidene/vinyl intermediates condense with an active-methyl heterocyclic quaternary salt to give a polymethine carbocyanine salt, or with a cyclic ketomethylene compound to give a merocyanine; substituents shown include }Y,Y',R,R',R'',X^-,Cl^-,\ (CH{=}CH)_n\text{]]} \end{array} \]

\[ n = 0\ \text{or}\ 1. \]

Thus, when triethylamine (0.21 g) was added to a solution of the chloroethylate of 2-β-chlorostyrylbenzothiazole (0.34 g) and the iodethylate of quinaldine (0.30 g) in methanol (2 ml), 3,1′-diethyl-9-phenylthia-2′-quinocarbocyanine iodide rapidly separated in almost quantitative yield (dark-green plates with a golden sheen, m.p. 256–257°). Found, %: J 22.62, \(C_{29}H_{27}N_2SJ\). Calculated, %: J 22.56.

Under analogous conditions, from salt II and 3-ethylrhodanine there was obtained, in 83% yield, 3-ethyl-5-(3′-ethylbenzothiazolinylidene-2′-α-methylethylidene)rhodanine with m.p. 215–216° \((^{17})\). From the chloroethylate of 2-δ-chloropentadienylbenzothiazole and the iodethylate of 2-methylbenzothiazole it was possible to obtain, in 70% yield, 3,3′-diethyl-9-methylthiadicarbocyanine iodide with m.p. 212–213° \((206–207^\circ\ (^{18}))\).

By this method, a great variety of carbo- and merocyanines were synthesized in high yields, in particular those containing in the meso-position—

an alkyl or aryl group. In this way it was possible to obtain many previously not readily accessible or not yet described dyes, in particular meso-alkyl- and arylindocarbocyanines, meso-phenyl-2,2′- and 2,4′-quinocarbocyanines (e.g., IX), α-methyl- and α-phenyldimethinmerocyanines, derivatives of thiohydantoin (e.g., X), coumaranone (e.g., XI), anilide of benzoylacetic acid, etc.

\[ \begin{aligned} &\text{(IX)} \qquad \text{(X)} \qquad \text{(XI)} \end{aligned} \]

Salt II and the corresponding β-chlorostyryl derivative also react with ethyl iodide of 2-ethylbenzthiazole, giving dyes XII \((R = CH_3 \text{ or } C_6H_5)\).

\[ \begin{aligned} &\text{(XII)} \qquad \text{(XIII)} \end{aligned} \]

The quaternary salts of 2-β-chlorovinyl derivatives of heterocyclic bases possess especially great reactivity. When phosgene acts on 2-formylmethylene-3-ethylbenzthiazoline in chloroform, the resulting chloroethylate of 2-β-chlorovinylbenzthiazole reacts with still unchanged formylmethylene derivative, giving the 8-formylthiacarbocyanine (XIII) previously described by Kendall \(^{19}\) and Nys \(^{20}\) (iodide—orange needles, m.p. 253–254°, absorption maximum in alcohol at 503 mμ).

After completion of the present work, an article by Zollinger and co-workers \(^{21}\) appeared; by the action of phosgene on 2-acetylmethylene-3-ethylbenzthiazoline in methylene chloride, they obtained the chloroethylate of 2-β-chloropropenylbenzthiazole and showed that, on its interaction with 3-methyl-2-methylenebenzthiazoline, 3,9-dimethyl-3′-ethylthiacarbocyanine chloride is formed.

All-Union Scientific Research
Institute of Cinematography

Received
3 VII 1962

CITED LITERATURE

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