L. N. D’yakonova-Shul’ts

On the Action of Tertiary Amines on Halo-Substituted Esters

(From the Laboratory of Organic Chemistry of the Siberian Chemical-Technological Institute)

The aim of the present investigation was to elucidate the mechanism of the reactions between halo-substituted esters and tertiary amines. Halogen-containing organic compounds are in general capable of adding to tertiary amines according to the scheme

\[ \mathrm{RN + R_{1}X \longrightarrow RN - R_{1},} \]
\[ \begin{array}{c} |\\ \mathrm{X} \end{array} \]

forming tetrasubstituted ammonium salts.

I investigated the following halo-substituted esters of monobasic and dibasic acids for their capacity to add to the tertiary amines pyridine and quinoline:

Methyl ester of \(\alpha\)-bromopropionic acid.
Ethyl ester of \(\alpha\)-bromopropionic acid.
Propyl ester of \(\alpha\)-bromopropionic acid.
Ethyl ester of \(\alpha\)-bromobutyric acid.
Methyl ester of \(\alpha\)-bromo-isobutyric acid.
Ethyl ester of \(\alpha\)-bromo-isobutyric acid.
Ethyl ester of \(\alpha\)-bromo-isovaleric acid.
Ethyl ester of \(\alpha\)-chloromalonic acid.
Ethyl ester of \(\alpha\)-bromomalonic acid.
Ethyl ester of methyl-chloromalonic acid.
Ethyl ester of methyl-bromomalonic acid.

The following literature may be cited on this question:

A. W. Hofmann \(^{1}\), on heating triethylamine and the ethyl ester of chloroacetic acid in a sealed tube for several hours to \(100^\circ\), obtained an addition product

\[ \begin{array}{c} (\mathrm{C_{2}H_{5}})_{3}\mathrm{N} - \mathrm{CH_{2}} - \mathrm{COOC_{2}H_{5}}\\ |\\ \mathrm{Cl} \end{array} \]

\(^{1}\) Jahresb. d. Chem. 1862, 333.

O. Rhoussopoulos¹) obtained

\[ \begin{array}{c} \mathrm{C_9H_7N}-\mathrm{CH_2}-\mathrm{COOC_2H_5}\\ \ \ \vert\\ \mathrm{Cl} \end{array} \]

by the action of ethyl chloroacetate on quinoline at ordinary temperature.

M. Krüger²) obtained, by the action of pyridine on chloroacetic ester at ordinary temperature, the crystalline compound

\[ \begin{array}{c} \mathrm{C_5H_5N}-\mathrm{CH_2}-\mathrm{COOC_2H_5},\\ \ \ \vert\\ \mathrm{Cl} \end{array} \]

which, when heated to \(110\text{–}115^\circ\), first melts to a yellow-red liquid and then decomposes with evolution of gases and a black coloration; the decomposition products were not investigated by him.

He also obtained, by the action of ethylpiperidine and \(\beta\)-picoline on chloroacetic ester, without heating, the following salts:

\[ \begin{array}{c} \mathrm{C_7H_{15}N}-\mathrm{CH_2}-\mathrm{COOC_2H_5}\\ \ \ \vert\\ \mathrm{Cl} \end{array} \qquad \text{and} \qquad \begin{array}{c} \mathrm{C_6H_7N}-\mathrm{CH_2}-\mathrm{COOC_2H_5}\\ \ \ \vert\\ \mathrm{Cl} \end{array} \]

H. Silberstein³) heated trichloroacetic ester and dimethylaniline in benzene solution; upon addition of ligroin he observed the separation of an oil which, according to his supposition, is:

\[ \begin{array}{c} \mathrm{CH_3}\\ \vert\\ \mathrm{C_6H_5N}-\mathrm{CCl_2}-\mathrm{COOC_2H_5}\\ \vert\!\!\diagdown \mathrm{Cl}\\ \mathrm{CH_3} \end{array} \]

E. Wedekind⁴) obtained the following salts:

\[ \begin{array}{c} (\mathrm{C_2H_5})_3\mathrm{N}-\mathrm{CH_2}-\mathrm{COOCH_3},\\ \ \ \vert\\ \mathrm{Cl} \end{array} \qquad \begin{array}{c} (\mathrm{C_2H_5})_3\mathrm{N}-\mathrm{CH_2}-\mathrm{COOCH_3},\\ \ \ \vert\\ \mathrm{J} \end{array} \]

\[ \begin{array}{c} \mathrm{CH_2}-\mathrm{C_6H_5}\\ \vert\\ \mathrm{C_5H_{10}N}-\mathrm{CH_2}-\mathrm{COOC_2H_5}\\ \vert\\ \mathrm{Cl} \end{array} \]

¹) Ber. 15, 2006.
²) Journ. f. pract. Chem [2] 43. 274, 369, 372.
³) Ber. 17, 2660.
⁴) Ann. Chem. 318, 104.

\[ \begin{array}{c} \mathrm{Br}\\ \big|\\ \mathrm{C_5H_{10}N{-}CH_2{-}COOC_2H_5,}\\ \big|\\ \mathrm{CH_2{-}C_6H_5} \end{array} \]

\[ \mathrm{C_9H_7N{-}CH_2{-}COOCH_3} \quad\text{and}\quad \begin{array}{c} \mathrm{CH_3}\\ \big|\\ \mathrm{C_6H_5N{-}CH_2{-}COOC_2H_5}\\ \big|\\[-2mm] \mathrm{J}\\ \big|\\[-2mm] \mathrm{CH_3} \end{array} \]

by the action of the corresponding esters on tertiary amines at room temperature.

H. Ihlder¹ obtained

\[ \begin{array}{c} \mathrm{C_9H_7N{-}CH_2{-}COOC_2H_5}\\ \big|\\ \mathrm{Br} \end{array} \]

by the action of quinoline on bromoacetic ester at room temperature.

I. Zimmermann² obtained

\[ \begin{array}{c} \mathrm{CH_3}\\ \big|\\ \mathrm{C_6H_5N{-}CH_2{-}COOC_2H_5}\\ \big|\\[-2mm] \mathrm{Cl}\\ \big|\\[-2mm] \mathrm{CH_3} \end{array} \]

by heating dimethylaniline and chloroacetic ester in a sealed tube to \(100^\circ\) for 4 hours.

ESTERS OF MONOBASIC ACIDS

EXPERIMENTS WITH PYRIDINE

Methyl ester of \(\alpha\)-bromopropionic acid.

On heating equimolecular quantities of pyridine and the ester on a water bath, already one minute after the start of heating the separation of a dark-brown oil was observed at the bottom of the vessel. After 15 minutes about 50% of the theoretical amount of oil had separated. After 40 minutes the entire mixture had turned into a thick, dark-brown, oily mass. After washing with ligroin, a yellow product was obtained. In order to obtain the substance in purer form, the experiment was conducted without heating, at room temperature. After 6 hours colorless crystals appeared in the form of needles. They separated from

of the reaction mixture, washed with petroleum ether, and dried in a desiccator over sulfuric acid. The crystalline product is hygroscopic, readily soluble in water, alcohol, and chloroform; it is insoluble in petroleum ether and gasoline.

Analysis: sample — 0.2111 g.
Obtained AgBr — 0.1600 g.
Calculated bromine for the formula

\[ \begin{array}{c} \mathrm{CH_3}\\ \big|\\ \mathrm{C_5H_5N{-}CH{-}COOCH_3}\ -\ 32.48\%\\ \big|\\ \mathrm{Br} \end{array} \]

Found — 32.21%.

The analysis indicates that the substance obtained is the product of addition of the ester to pyridine, i.e., the reaction proceeds according to the equation:

\[ \mathrm{C_5H_5N + CH_3{-}CHBr{-}C(=O)OCH_3 \longrightarrow \begin{array}{c} \mathrm{C_5H_5N{-}Br}\\ \big|\\ \mathrm{CH{-}COOCH_3}\\ \big|\\ \mathrm{CH_3} \end{array}} \]

Ethyl Ester of \(\alpha\)-Bromopropionic Acid

When 18.2 g of the ester is added to 9 g of pyridine (equimolecular amounts) in the presence of petroleum ether at room temperature, a change in the color of the liquid occurs at once. It begins to take on a yellow coloration and to thicken. After 2 hours, a thick yellow oil appears at the bottom of the vessel. The reaction product is separated from the reaction mixture, triturated with gasoline using a pestle, and placed in a desiccator over sulfuric acid. After standing for two days in the desiccator, the substance turns into a solid mass, which readily liquefies in air. The oil dissolves in water, alcohol, and chloroform, and is insoluble in ether and gasoline.

Analysis: sample — 0.2400 g.
Obtained AgBr — 0.1717 g.

Calculated bromine for the formula

\[ \begin{array}{c} \mathrm{Br}\\ \big|\\ \mathrm{C_5H_5N{-}CH{-}COOC_2H_5}\ -\ 30.75\%\\ \big|\\ \mathrm{CH_3} \end{array} \]

Found 30.45%.

Analysis indicates that the reaction proceeds according to the equation:

\[ \mathrm{C_5H_5N + CH_3 - CHBr - COOC_2H_5 \longrightarrow \underset{\mathrm{Br}}{\mathrm{C_5H_5N}} - \underset{\mathrm{CH_3}}{\mathrm{CH}} - \mathrm{COOC_2H_5}} \]

Propyl ester of $\alpha$-bromopropionic acid.

For the experiment, equimolecular quantities of pyridine and ester were taken. The reaction was carried out in the presence of petroleum ether at room temperature. After two hours a yellow oil appeared at the bottom of the vessel. It readily resinifies in air, is insoluble in petroleum ether and gasoline, and is readily soluble in water, alcohol, and chloroform. The reaction product is separated from the reaction mixture, triturated with gasoline, the traces of gasoline are removed by blowing air through, and it is then placed in a desiccator over sulfuric acid. On standing in the desiccator the substance turns into a crystalline mass of yellow color.

Analysis: sample—0.2107 g.
Obtained AgBr—0.1431 g.

\[ \text{Calculated bromine for the formula } \underset{\mathrm{Br}}{\mathrm{C_5H_5N}} - \underset{\mathrm{CH_3}}{\mathrm{CH}} - \mathrm{COOC_3H_7} \text{—} 29.16\% \]

found 28.90%.

Ethyl ester of $\alpha$-bromobutyric acid.

On adding 19.6 g to 8.5 g of pyridine (equimolecular quantities), the reaction mixture becomes colored pale yellow. The reaction is carried out in a flask connected with a vertical tube, with heating in a thermostat to $80^\circ$ for 5 hours. After 40 minutes, an oil of red color appeared at the bottom of the flask, about 60% of theory; after 3 hours, 70%; after 4 hours, 82%. When the reaction is carried out in the presence of petroleum ether at room temperature, a light-colored oil separates. It is separated from the liquid, washed with petroleum ether, triturated with gasoline, and placed in a desiccator over sulfuric acid.

Analysis: sample 0.2231 g.
Obtained AgBr—0.1531 g.

\[ \text{Required for } \underset{\mathrm{Br}}{\mathrm{C_5H_5N}} - \underset{\substack{\mathrm{CH_2}\\|\\\mathrm{CH_3}}}{\mathrm{CH}} - \mathrm{COOC_2H_5} \text{—} 29.16\% \]

Found bromine 29.18%.

On the basis of the analysis, the reaction proceeds as follows:

\[ \mathrm{C_5H_5N + CH_3 - CH_2 - CHBr - COOC_2H_5 \longrightarrow \underset{\mathrm{Br}}{\mathrm{C_5H_5N}} - \underset{\mathrm{COOC_2H_5}}{\mathrm{CH}} - \mathrm{CH_2} - \mathrm{CH_3}} \]

Methyl ester of α-bromo-isobutyric acid.

The reaction is carried out in a flask connected with a vertical tube, with heating in a thermostat to 80° for 10 hours. After 30 minutes, drops of yellow oil fell on the bottom of the flask. When the reaction was conducted for 94 hours at room temperature, about 3% of the theoretical amount of oil separated. The oil is separated from the mixture, washed and triturated with ligroin, and dried in a desiccator over sulfuric acid.

Analysis: sample 0.2133 g.
Obtained AgBr — 0.1533 g.

Calculated bromine for

\[ \mathrm{C_5H_5N{-}\underset{\substack{|\\ \mathrm{CH_3}}}{\overset{\substack{\mathrm{CH_3}\\ |}}{C}}{-}COOCH_3} \quad \begin{matrix} \\[-2.2em] |\\ \mathrm{Br} \end{matrix} \]

— 30.75%

Found — 30.56%

Consequently, the reaction proceeds according to the equation:

\[ \mathrm{C_5H_5N + CH_3{-}\underset{\substack{|\\ \mathrm{CH_3}}}{CBr}{-}COOCH_3 \rightleftarrows C_5H_5N{-}\underset{\substack{|\\ \mathrm{Br}}}{\overset{\substack{\mathrm{CH_3}\\ |}}{C}}{-}COOCH_3} \]

\[ \mathrm{ \phantom{C_5H_5N + CH_3{-}} \underset{\mathrm{CH_3}}{\phantom{CBr}} \qquad\qquad \phantom{C_5H_5N{-}} \underset{\mathrm{CH_3}}{\phantom{C}} } \]

Ethyl ester of α-bromo-isobutyric acid.

When equimolecular quantities of the reacting substances are mixed in a flask connected with a vertical tube, a change in the color of the liquid occurs.

When the flask was heated in a thermostat to 80° for 40 minutes, about 10% of the theoretical amount of a yellow-red oil separated. After 11 hours about 19% separated. When the reaction was carried out at room temperature for 94 hours, about 2% of a light-yellow oil separated. It is separated from the reaction mixture, washed with ligroin, triturated with ethyl ether, and placed in a desiccator over sulfuric acid. The reaction product is hygroscopic, insoluble in ether and ligroin, and soluble in water, alcohol, and chloroform.

Analysis: sample 0.2053 g.
Obtained 0.1396 g AgBr.

Calculated bromine for

\[ \mathrm{C_5H_5N{-}\underset{\substack{|\\ \mathrm{CH_3}}}{\overset{\substack{\mathrm{CH_3}\\ |}}{C}}{-}COOC_2H_5} \quad \begin{matrix} \\[-2.2em] |\\ \mathrm{Br} \end{matrix} \]

— 29.16%

Found 28.93%.

Ethyl ester of α-bromo-isovaleric acid.

Into a flask connected with a vertical tube are introduced 4.5 g of pyridine (an excess of 0.5 g) and 10.5 g of the ester (equimolecular amounts). On mixing, the liquid acquires a yellow tint. The flask is then placed in a thermostat and heated to \(80^\circ\) for 15 hours. After 40 minutes, drops of a syrup-like yellow substance separated on the bottom and walls of the flask. After 4 hours about 15% had separated; after \(13^{1/2}\) hours—17.1%. The reaction product is separated from the mixture, washed and triturated with ligroin, and placed in a desiccator over sulfuric acid.

The substance obtained is hygroscopic, readily soluble in water, alcohol, and chloroform, and insoluble in ligroin and petroleum ether.

Analysis for halogen gave a poor result; in view of this, a second experiment was carried out without heating, at room temperature, in the presence of petroleum ether. After several days, a yellow oily substance separated. It was repeatedly washed with ether and kept in a desiccator over sulfuric acid.

Analysis: Sample 0.2395 g. Obtained 0.1563 g AgBr.

Calculated bromine for

\[ \begin{array}{c} \mathrm{C_5H_5N} - \mathrm{CH} - \mathrm{COOC_2H_5} \\ \vert \qquad \vert \\ \mathrm{Br} \qquad \mathrm{CH} - \mathrm{CH_3} \\ \qquad\quad \vert \\ \qquad\quad \mathrm{CH_3} \end{array} \]

27.75%.

Found 27.76%.

Thus, the analysis indicates that the reaction proceeds according to the equation:

\[ \begin{array}{c} \mathrm{C_5H_5N} + \mathrm{CH_3} - \mathrm{CH} - \mathrm{CHBr} - \mathrm{COOC_2H_5} \longrightarrow \mathrm{C_5H_5N} - \mathrm{CH} - \mathrm{COOC_2H_5} \\ \qquad\qquad\quad \vert \qquad\qquad\qquad\qquad\qquad\quad \vert \qquad \vert \\ \qquad\qquad\quad \mathrm{CH_3} \qquad\qquad\qquad\qquad\qquad \mathrm{Br} \qquad \mathrm{CH} - \mathrm{CH_3} \\ \qquad\qquad\qquad\qquad\qquad\qquad\qquad\qquad\qquad\quad \vert \\ \qquad\qquad\qquad\qquad\qquad\qquad\qquad\qquad\qquad\quad \mathrm{CH_3} \end{array} \]

EXPERIMENTS WITH QUINOLINE.

Methyl ester of α-bromopropionic acid.

When 16 g of quinoline are added to 20.7 g of the ester (mole for mole), the reaction mixture is colored almost instantaneously at ordinary temperature pink, and after 30 minutes yellow-red. After some time, a red oily substance separates. After a month, about 13.6% of the theoretical amount of the oil had separated. When the experiment is conducted in a sealed tube, a thick red syrup separates. If the reaction is carried out in the presence of petroleum ether, the oil obtained is yellow.

The reaction product is separated from the liquid, washed with ligroin, and dried in a desiccator over sulfuric acid. On standing in the desiccator in

for two months the oil did not crystallize. The oil spreads readily in air, dissolves in water, alcohol, and chloroform, and does not dissolve in gasoline.

Analysis:

Sample 0.1802 g; obtained 0.1135 AgBr

Calculated bromine for

\[ \begin{array}{c} \mathrm{C_9H_7N-CH-COOCH_3} \quad -\ 27.00\%\\ \quad | \quad |\\ \quad \mathrm{Br}\quad \mathrm{CH_3} \end{array} \]

Found 26.79%.

Ethyl ester of α-bromopropionic acid.

When equimolecular amounts of the ester and quinoline are mixed, the liquid first becomes pale pink and then red. The reaction is conducted in a flask connected with a vertical tube, with heating in a thermostat at 80° for one hour.

After 15 minutes the liquid acquired a dark-red color. After 45 minutes a red oil separated; it is separated from the remaining liquid, washed and triturated with gasoline, and dried in a desiccator over sulfuric acid.

The product obtained is hygroscopic, insoluble in ether and gasoline, soluble in water, alcohol, and chloroform.

When the reaction is conducted at ordinary temperature in the presence of petroleum ether, an oil colored yellow was obtained. On standing for a month, 12.5% of the theoretical amount of substance separated.

Analysis:

Sample 0.2191 g. Obtained—0.1264 g AgBr.

Calculated bromine for

\[ \begin{array}{c} \mathrm{Br}\\ |\\ \mathrm{C_9H_7N-CH-COOC_2H_5} \quad 25.79\%.\\ |\\ \mathrm{CH_3} \end{array} \]

Found—25.54%.

Propyl ester of α-bromopropionic acid.

If the ester and quinoline are mixed in equimolecular proportions at room temperature, the liquid first becomes pink, then brown-red. On standing for a month in a desiccator over sulfuric acid, a crust of hard, large crystals formed, which adhered very firmly to the walls of the flask. The crust of crystals is separated from the mother liquor; washed with petroleum ether, acetone, then again with petroleum ether. The reaction product is ground to a fine yellow powder, washed with gasoline, pressed on a clay ...

plate and dried in a desiccator over sulfuric acid. The substance dissolves readily in water, alcohol, and chloroform; it does not dissolve in ethyl ether or gasoline.

Analysis: sample 0.2108 g.

Obtained—0.1221 g AgBr.

Calculated bromine for the formula

\[ \begin{array}{c} \mathrm{Br}\\ |\\ \mathrm{C_9H_7{-}N{-}COOC_3H_7}\\ |\\ \mathrm{CH_3} \end{array} \]

—24.67%.

Found—24.62%.

Ethyl ester of α-butyric acid.

If the ester is heated with quinoline in equimolecular amounts in a flask connected to a vertical tube, in a thermostat at 80° for 35 hours, the mixture first becomes red, and then a dark-red oil precipitates.

When the experiment is carried out at ordinary temperature for 22 hours, about 11% of the theoretical amount of oil precipitated. The oil is treated with gasoline; on standing in a desiccator over sulfuric acid the substance crystallized.

The reaction product is readily soluble in water, alcohol, and chloroform, and insoluble in ethyl ether and gasoline.

Analysis: sample 0.2143 g.

Obtained 0.1231 g AgBr.

Calculated bromine for the formula

\[ \begin{array}{ccccc} \mathrm{C_9H_7N} & {-} & \mathrm{CH} & {-} & \mathrm{COOC_2H_5}\\ | & & | & & \\ \mathrm{Br} & & \mathrm{CH_2} & & \\ & & | & & \\ & & \mathrm{CH_3} & & \end{array} \]

24.67%.

Found 24.45%.

Methyl ester of α-bromoisobutyric acid.

If the reaction is conducted at ordinary temperature, the reaction mixture first becomes brown-red in color, and then an oily red substance separates. Over the course of 14 days, about 2% of the theoretical amount of oil precipitated. It is separated from the liquid and washed with petroleum ether. On standing in a desiccator over sulfuric acid,

with acid for three weeks, the substance did not crystallize. The reaction product dissolves readily in water, alcohol, and chloroform; it does not dissolve in gasoline or ether.

Analysis: sample 0.2367 g.

Obtained 0.1417 g AgBr.

Calculated bromine for

\[ \begin{array}{c} \mathrm{CH_3}\\ |\\ \mathrm{C_9H_7N{-}C{-}COOCH_3}\\ \phantom{\mathrm{C_9H_7N}}\;|\;\phantom{\mathrm{COOCH_3}}\\ \mathrm{Br}\quad \mathrm{CH_3} \end{array} \]

25.79%.

Found 25.47%.

Ethyl ester of α-bromoisobutyric acid.

For the experiment, 15.1 g of the ester and 11.5 g of quinoline were taken. The reaction mixture, placed in a flask with a vertical tube, was heated in a thermostat at 80°. Over the course of 10 hours, a layer of a syrup-like red substance, about 24% of theory, separated at the bottom of the flask. When the reaction was carried out at room temperature for 20 days, a yellow-red oil separated, about 2% of theory. It is separated from the liquid, washed with gasoline, and dried in a desiccator over sulfuric acid. On standing in the desiccator for 2 months, the oil did not crystallize. The substance obtained is hygroscopic and dissolves readily in ether and gasoline.

Analysis: sample 0.1474 g.

Obtained 0.0846 g AgBr.

Calculated bromine for the formula

\[ \begin{array}{c} \mathrm{CH_3}\\ |\\ \mathrm{C_9H_7N{-}C{-}COOC_2H_5}\;-\;24.67\%\\ \phantom{\mathrm{C_9H_7N}}\;|\;\phantom{\mathrm{COOC_2H_5}}\\ \mathrm{Br}\quad \mathrm{CH_3} \end{array} \]

Found—24.42%.

Ethyl ester of α-bromoisovaleric acid.

On adding the ester to quinoline (equimolecular quantities), the reaction mixture turns pink. If the mixture is heated in a thermostat to 80°, then after 30 minutes the liquid acquires a dark-red color. After 9 hours, a red oil separates at the bottom of the flask, about 2.5% of theory. When the reaction is carried out at room temperature, the liquid turns brown-red. After standing for a month in a desiccator over sulfuric acid, a yellow-red substance separated. It is separated from the liquid, washed, and triturated with gasoline. On standing in a cabinet

over sulfuric acid for a month, the oil did not crystallize. The compound obtained readily resinifies in air, dissolves in water, alcohol, and chloroform, and does not dissolve in ether or gasoline.

Analysis: sample 0.1997 g.
Obtained 0.1094 g AgBr.

Calculated bromine for the formula:

$$ \begin{array}{c} \mathrm{C_9H_7N{-}CH{-}COOC_2H_5} \\ \phantom{\mathrm{C_9H_7N{-}}}\vert \\ \phantom{\mathrm{C_9H_7N{-}}}\mathrm{Br} \end{array} \quad \begin{array}{c} \phantom{\mathrm{{-}CH{-}}}\vert \\ \mathrm{CH{-}CH_3} \\ \vert \\ \mathrm{CH_3} \end{array} \qquad 23.64\%. $$

Found 23.28%.

ESTERS OF DIBASIC ACIDS.

EXPERIMENTS WITH PYRIDINE.

Ethyl ester of chloromalonic acid.

When equimolecular quantities of pyridine and ethyl chloromalonate are mixed at room temperature in the presence of petroleum ether, the liquid turns yellow. After 24 hours a light-yellow oil separated; it is separated from the reaction mixture, washed with petroleum ether, triturated with gasoline, and dried in a desiccator over sulfuric acid. The reaction product is hygroscopic, readily soluble in water, alcohol, and acetone; insoluble in ether and gasoline. On the action of an alcoholic solution of chloroplatinic acid upon the obtained substance, the latter at first dissolves, and then a crystalline precipitate of yellow color separates. The precipitate is filtered off, washed with cold water, and recrystallized from hot alcohol. On recrystallization, yellow needle-shaped crystals separate, poorly soluble in water and ether, fairly readily in hot, dilute alcohol.

Analyses:
I. Sample 0.2470 g. After ignition obtained Pt—0.0535 g.
II. Sample 0.0924 g. After ignition obtained Pt—0.0193 g.

Calculated Pt for the compound

$$ \left[ \mathrm{C_5H_5N{-}CH(COOC_2H_5)_2} \begin{array}{c} \diagup \mathrm{Cl} \end{array} \right]_2 \mathrm{PtCl_4} \;-\;22.04\%. $$

Found:
I—21.65%.
II—21.96%.

The analyses indicate that the product obtained is:

$$ \begin{array}{c} \mathrm{C_5H_5N{-}CH{-}COOC_2H_5} \\ \phantom{\mathrm{C_5H_5N{-}}}\vert \quad \vert \\ \phantom{\mathrm{C_5H_5N{-}}}\mathrm{Cl}\quad \mathrm{COOC_2H_5} \end{array} $$

Ethyl ester of bromomalonic acid.

If pyridine and bromomalonic ester are mixed in equimolecular amounts at ordinary temperature, a change in the color of the mixture occurs at once. The initially completely colorless liquid acquires a yellow tint, after an hour turns red, and after two hours a thick, syrup-like red layer forms at the bottom of the flask. After 12 hours almost the entire liquid is converted into a thick dark-red oil. The yield is about 90% of theory. The substance is washed with gasoline and dried in a desiccator over sulfuric acid.

Analysis gave a bromine content of 23.16%, whereas for the formula

\[ \begin{gathered} \mathrm{C_5H_5N - CH - (COOC_2H_5)_2}\\ \phantom{\mathrm{C_5H_5N -}}\big|\\ \mathrm{Br} \end{gathered} \]

bromine is calculated as 25.13%. To obtain a better result the reaction was carried out in the presence of petroleum ether. A thick yellow oil separates. It is repeatedly washed with ether, triturated with gasoline, and dried in a desiccator over sulfuric acid.

Analysis: sample 0.2867 g. Obtained 0.1675 g AgBr.
Bromine calculated according to the above formula: 25.13%
Found — 24.87%
The analytical data correspond to the formula:

\[ \begin{gathered} \mathrm{C_5H_5N - CH - (COOC_2H_5)_2}\\ \phantom{\mathrm{C_5H_5N -}}\big|\\ \mathrm{Br} \end{gathered} \]

The product is extremely hygroscopic, readily soluble in water, alcohol, and acetone, and insoluble in gasoline and ether.

Ethyl ester of methylchloromalonic acid.

On adding 5.6 g of pyridine to 15 g of the ester (equimolecular amounts), the reaction mixture first turns yellow, then yellow-red. After standing for five days at ordinary temperature, a light-red oil, about 2–3% of theory, separated at the bottom of the flask. After standing for a month in a desiccator over sulfuric acid, crystals formed and about 22% of oil separated. If the reaction is carried out in the absence of atmospheric moisture, i.e. in a sealed tube at room temperature, then oil and crystals likewise separate. By means of petroleum ether the crystals and oil were separated from the unreacted mixture. The crystals were purified with acetone, in which the oil dissolves more readily. After removal of the acetone the oil was washed with petroleum ether and kept in a desiccator over sulfuric acid. After purification the substance was obtained

yellow in color. It melts readily in air, dissolves well in water, acetone, and alcohol, and does not dissolve in ether or ligroin.

Analysis of the oil: sample 0.2126 g; 0.1065 g obtained.
Chlorine found, 12.37%; required for

\[ \begin{array}{c} \mathrm{C_5H_5N}-\mathrm{C}-(\mathrm{COOC_2H_5})_2 \;—\; 12.32\%.\\ \big| \qquad \big|\\ \mathrm{Cl}\qquad \mathrm{CH_3} \end{array} \]

The crystals, freed from oil, were washed with ligroin and dried in a desiccator over sulfuric acid. The crystalline substance is hygroscopic, dissolves readily in water and alcohol, with difficulty in acetone, and does not dissolve in ether or ligroin.

Analysis of the crystals: sample 0.2142 g. 0.2148 AgCl obtained.
Chlorine calculated for

\[ \mathrm{C_5H_5N}\!-\!\overset{\mathrm{Cl}}{\mathrm{C_2H_5}} \;—\; 24.66\% \]

Found 24.78%.

Ethylpyridinium chloride is evidently the product of a side reaction.

Ethyl ester of methyl-bromomalonic acid.

When equimolecular amounts of pyridine and the ester were heated in a thermostat to 30° for 2 hours, an oily substance of brown color separated. At ordinary temperature, after standing for three days, a small amount of yellow oil precipitated. The precipitated product is hygroscopic, readily soluble in water, alcohol, and acetone, and insoluble in ethyl ether and ligroin. The oil was separated from the reaction mixture, washed with petroleum ether, triturated with ligroin, and dried in a desiccator over sulfuric acid.

Analysis: sample 0.3160 g. 0.1770 g AgBr obtained.
Bromine calculated for the formula

\[ \begin{array}{c} \mathrm{C_5H_5N}-\mathrm{C}-(\mathrm{COOC_2H_5})_2 \;—\; 24.07\%.\\ \big| \qquad \big|\\ \mathrm{Br}\qquad \mathrm{CH_3} \end{array} \]

Found—23.82%.

EXPERIMENTS WITH QUINOLINE.

Ethyl ester of chloromalonic acid.

In the interaction of chloromalonic ester with quinoline, an addition product is likewise evidently formed, which, however, decomposes immediately; therefore it was not possible to isolate it.

Ethyl ester of bromomalonic acid.

When equimolecular amounts of bromomalonic ester and quinoline are mixed at ordinary temperature, the mixture after 2–3 minutes becomes pink, and after 5–10 minutes red. On the fifth day the mixture thickens and takes on the appearance of a syrup; on the 8th day the mixture turns into a thick oil. It is separated and washed free of the reaction mixture with the aid of petroleum ether. The oil is readily decomposed in air, dissolves in water, alcohol, and acetone, and does not dissolve in petroleum ether or gasoline. It is kept in a desiccator over sulfuric acid.

Analysis: sample 0.2088 g.
Obtained 0.1034 g AgBr.
Calculated bromine for the formula

\[ \begin{gathered} \mathrm{C_9H_7N{-}CH{-}(COOC_2H_5)_2} \;-\; 21.71\% \\ \big| \\ \mathrm{Br} \end{gathered} \]

Found—21.07%.

When the reaction is carried out in a sealed flask, in the absence of atmospheric moisture, at ordinary temperature for 10 days, a red coloration of the liquid and the appearance, on the 6th day, of a red oil were observed. On opening the flask, the evolution of a small amount of carbon dioxide was detected.

The reaction product is separated from the liquid, washed with ether, and triturated with gasoline. After purification and standing in a desiccator, the oil changed into a solid substance of light-red color.

Analysis: sample 0.2243 g.
Obtained 0.1120 g AgBr.
Calculated bromine for the above-mentioned formula 21.71%.
Found—21.22%.

The best result is achieved when the reaction is carried out in the presence of petroleum ether at ordinary temperature.

A thick yellow oil precipitates, which on standing in a desiccator turns into a solid mass.

Analysis: sample 0.2092 g.
Obtained 0.1053 g AgBr.
Found bromine 21.36%.

It follows for

\[ \begin{gathered} \mathrm{C_9H_7N{-}CH{-}(COOC_2H_5)_2} \;-\; 21.71\% \\ \big| \\ \mathrm{Br} \end{gathered} \]

Analysis indicates that the reaction proceeds according to the equation:

\[ \begin{gathered} \mathrm{C_9H_7N + CH{-}(COOC_2H_5)_2 \longrightarrow C_9H_7N{-}CH{-}(COOC_2H_5)_2} \\ \big| \hspace{6.5cm} \big| \\ \mathrm{Br} \hspace{6.5cm} \mathrm{Br} \end{gathered} \]

Ethyl Ester of Methyl-chloromalonic Acid

The reaction of methyl-chloromalonic ester with quinoline proceeds extremely slowly. On prolonged standing in a desiccator, no traces of reaction are noticeable. When heated in a thermostat to \(40^\circ\) for 2 hours, the mixture turns yellow, and after 60 hours red. After 80 hours the liquid thickens. After 105 hours, upon addition of petroleum ether, a dark oil precipitated at the bottom of the flask. After 125 hours, crystals separated in the form of yellow needles, about 6.6% of theory. The oil and crystals are separated from the mixture and washed with gasoline. The crystals are isolated by means of acetone. The crystalline product is faintly yellow, readily soluble in water and alcohol, sparingly in acetone, and insoluble in ether and gasoline. It readily melts in air, and therefore is kept in a desiccator over sulfuric acid.

Analysis of the crystals: sample 0.2293 g; obtained 0.1730 g AgCl.
Calculated chlorine for the formula

\[ \mathrm{C_9H_7N\!-\!\underset{C_2H_5}{\overset{Cl}{-}}\!-\!C_2H_5} = 18.32\% \]

Found — 18.62%.

Analysis of the oil: sample 0.1575 g; obtained 0.0824 g AgCl.
Calculated chlorine for

\[ \begin{array}{c} \mathrm{C_2H_5} \\ \mathrm{C_9H_7N\!-\!C\!-\!COOC_2H_5} \\ \mathrm{\ \ \ \ \vert\ \ \vert} \\ \mathrm{\ \ \ Cl\ \ CH_3} \end{array} = 12.07\% \]

Found — 11.30%.

The analytical data indicate that the oily substance obtained contains impurities. It was not possible to isolate it in a purer state because of a shortage of methyl-chloromalonic ester.

It was not possible to obtain the addition product of methyl-chloromalonic ester to quinoline. In the interaction of the reacting substances, at the first moment, an addition product is probably formed, but upon slight heating and prolonged standing it decomposes with elimination of one molecule of carbonic acid, forming:

\[ \begin{array}{c} \mathrm{C_2H_5} \\ \mathrm{C_9H_7N\!-\!C\!-\!COOC_2H_5} \\ \mathrm{\ \ \ \ \vert\ \ \vert} \\ \mathrm{\ \ \ Cl\ \ CH_3} \end{array} \]

while at the same time ethyl chloride was evolved. The latter reacted with quinoline, giving ethylquinolinium chloride.

Ethyl Ester of Methyl-bromomalonic Acid

The reaction of methyl-bromomalonic ester with quinoline proceeds slowly. Upon standing for one month at ordinary temperature, only coloration of the mixture to a yellow-red color occurred.

Upon heating in a thermostat for 64 hours at \(40^\circ\), the liquid acquired a dark-red color. On addition of petroleum ether, a small amount of red oil separated. The reaction product is hygroscopic, soluble in water and alcohol, insoluble in gasoline. The substance is separated from the liquid, washed with petroleum ether, triturated with gasoline, and kept in a desiccator over sulfuric acid.

Analysis: sample 0.1505 g.

Obtained 0.0727 g AgBr.

Calculated bromine for

\[ \begin{array}{c} \mathrm{C_9H_7N - C - (COOC_2H_5)_2}\quad 20.93\%\\ \phantom{\mathrm{C_9H_7N}}\ \ \vert \quad \vert\\ \phantom{\mathrm{C_9H_7N}}\ \ \mathrm{Br}\quad \mathrm{CH_3} \end{array} \]

Found—20.46%

Thus, in the interaction of halo-substituted esters with tertiary amines, tetra-substituted halide ammonium salts are formed.

As regards the influence on the course of the reaction of the composition and structure of the reacting substances, the experimental material obtained permits the following conclusions to be drawn:

1. Halo-substituted esters react more rapidly with pyridine than with quinoline.

2. The longer the carbon chain of the alcohol and acid radical, the lower the rate of interaction with tertiary amines; for example:

\[ \mathrm{CH_3 - CHBr - COOC_2H_5} \]

reacts more slowly than \(\mathrm{CH_3 - CHBr - COOCH_3}\);

\[ \mathrm{CH_3 - CH_2 - CHBr - COOC_2H_5} \]

more slowly than \(\mathrm{CH_3 - CHBr - COOC_2H_5}\).

1. The position of the halide in the carbon chain also affects the rate of interaction with tertiary amines. Esters with the halide at the tertiary unit react more slowly than esters with the halide at the secondary unit,

thus,

\[ \begin{array}{c} \mathrm{CH_3 - CBr - C(=O)}\\ \phantom{\mathrm{CH_3 - CBr - C}}\backslash \mathrm{OC_2H_5}\\ \phantom{\mathrm{CH_3 -}}\vert\\ \phantom{\mathrm{CH_3 -}}\mathrm{CH_3} \end{array} \]

reacts more slowly, \(\mathrm{CH_3—CH_2—CHBr—COOC_2H_5}\);

\[ \begin{array}{c} \mathrm{BrC—(COOC_2H_5)_2}\\ \vert\\ \mathrm{CH_3} \end{array} \]

more slowly

\[ \begin{array}{c} \mathrm{C}\!\begin{array}{c} \!\!=\!\mathrm{O}\\[-0.2em] \!\!\backslash\mathrm{OC_2H_5} \end{array}\\ \vert\\ \mathrm{CHBr}\\ \vert\\ \mathrm{COOC_2H_5} \end{array} \]

4. Bromo-substituted esters react more rapidly than chloro-substituted ones.

1. Arch. d. Pharm. 240, 517. ↩

2. Ber. 12, 2206. ↩