Abstract
Full Text
Chemistry
Corresponding Member of the Academy of Sciences of the USSR A. P. Terent’ev,
M. A. Volodina, V. A. Kudryashova
STRUCTURE OF SCHIFF BASES OF N-ARYLPYRROLINES
In the reaction of α-(2-chloroethyl)-β-chlorocrotonaldehyde I with aqueous solutions of hydrochlorides of aromatic amines (ArNH₂·HCl), we obtained Schiff bases of N-arylpyrrolines (ShOP) (¹). The structure of ShOP may be represented by two formulas (II) and (III).
\[ \begin{array}{c} \mathrm{CH_3{-}C(Cl){=}C(CH_2CH_2Cl){-}C(=O)H} \\ \text{(I)} \\[0.5em] \downarrow\ \mathrm{ArNH_2\cdot HCl} \\[0.5em] \begin{array}{cc} \text{(II)} & \text{(III)} \end{array} \end{array} \]
\[ \begin{array}{c} (\mathrm{Ar}=: \text{a) } \mathrm{C_6H_5},\ \text{b) } n\text{-}\mathrm{CH_3C_6H_4},\ \text{c) } n\text{-}\mathrm{CH_3OC_6H_4},\ \text{d) } n\text{-}\mathrm{C_2H_5OC_6H_4},\ \text{e) } n\text{-}\mathrm{BrC_6H_4} \\ \text{f) } n\text{-}\mathrm{NO_2C_6H_4},\ \text{g) } m\text{-}\mathrm{NO_2C_6H_4},\ \text{h) } \alpha\text{-}\mathrm{C_{10}H_7},\ \text{i) } (\mathrm{C_2H_5})_2\mathrm{NC_6H_4}) \end{array} \]
A more detailed study of the reaction of I with ArNH₂·HCl made it possible to note certain features. In the reaction of I with hydrochlorides of aniline or of aromatic amines containing electron-acceptor substituents in the nucleus, the formation of a single, principal reaction product was observed. In the reaction of I with ArNH₂·HCl containing electron-donor substituents in the nucleus, the formation, along with the principal product, of a side reaction product was observed and proved by chromatography on aluminum oxide; the amount of this product for different amines varies from 3 to 20%. The principal and side reaction products in each individual case were separated chromatographically on aluminum oxide. The data of elemental analysis of each pair of separated substances confirm the identity of these compounds. On this basis it may be assumed that the principal and side reaction products are either cis–trans isomers with respect to the newly formed C=N bond, or the isomeric compounds II and III.
Hydrogenation of IIa in methanol over Raney Ni led to the formation of a mixture of reaction products. From this mixture, along with the normal product of complete hydrogenation of ShOP, products of ShOP cleavage at the C=N bond were isolated: aniline and N-phenylalkylpyrrolidine with the formula C₁₂N₁₇N. The NMR spectrum of N-phenylalkylpyrrolidine, recorded in carbon tetrachloride on a JNM-C-60 NMR spectrometer (60 MHz), showed the presence in this compound of two methyl groups, i.e., established the structure of the resulting N-phenylalkylpyrrolidine as N-phenyldimethylpyrrolidine V (Fig. 1). Thus, on the basis of the NMR spectrum, and also on the basis—
On the basis of structure I it may be considered proven that the synthesized Schiff bases of pyrrolines (the main reaction products) have structure II. The structure of the by-products of the reaction of I with ArAH is subject to further investigation.
Experimental Part
All Schiff bases of pyrrolines (SBP) were obtained by a single procedure (Table 1—main reaction products; Table 2—by-products of the reaction). In most cases the SBP were isolated as hydrochlorides, from which the bases were then obtained and characterized as picrates. In those cases where the SBP hydrochlorides were noncrystallizing oils, the SBP were obtained as bases, bypassing the stage of isolation of the corresponding hydrochlorides.
Hydrochlorides of SBP. To a concentrated aqueous solution of the hydrochloride of an aromatic amine (ArAH), I was added dropwise with shaking (the molar ratio I : ArAH was 1 : 2.2). After all of I had been added, the reaction mixture was shaken for another 30–40 min and left for 24 h at room temperature. The precipitate of the SBP hydrochloride was filtered off, washed with a small amount of cold water and ether, and recrystallized several times from water or from aqueous solutions of methanol or ethanol. For analysis it was dried in vacuo over \( \mathrm{P_2O_5} \) with heating.
Fig. 1. NMR spectrum of 2,3-dimethyl-1-phenylpyrrolidine
SBP bases were obtained by treating aqueous solutions of recrystallized SBP hydrochlorides with a dilute solution of sodium hydroxide; if necessary, they were reprecipitated from acetone or methanol with water and dried in vacuo over KOH (without heating). In those cases where the SBP hydrochloride separated as a noncrystallizing oil, the aqueous layer was carefully decanted, the oily residue was dissolved in methanol or acetone, diluted with a large amount of water, and treated with dilute sodium hydroxide solution. The precipitated greenish-yellow precipitate of the SBP base was filtered off, washed with a large amount of water, and reprecipitated from acetone or methanol with water. It was dried in vacuo over KOH (without heating).
Table 1
| Compound No. | Ar | Derivatives | Yield, % | m.p., °C | $P_f$ acetic acid : petr. ether | $R_f$ benzene : acetone | Found, % C | Found, % H | Found, % N | Found, % Cl | Empirical formula | Calculated, % C | Calculated, % H | Calculated, % N | Calculated, % Cl |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| II$_a$ | C$_6$H$_5$ | Hydrochloride | 96.7 | 217–218 | 72.36 72.57 |
6.70 6.75 |
9.28 9.21 |
11.44 12.12 |
C$_{18}$H$_{18}$N$_2$·HCl | 72.36 | 6.41 | 9.38 | 11.87 | ||
| II$_a$ | C$_6$H$_5$ | Base | 96.7 | 105 | 0.53 (1 : 1) |
0.36 (4 : 1) |
C$_{18}$H$_{18}$N$_2$ | ||||||||
| II$_a$ | C$_6$H$_5$ | Picrate | 96.7 | 227–228 | 58.78 58.62 |
4.30 4.18 |
14.39 14.25 |
C$_{18}$H$_{18}$N$_2$·C$_6$H$_3$N$_3$O$_7$ | 58.64 | 4.31 | 14.25 | ||||
| II$_b$ | $n$-CH$_3$C$_6$H$_4$ | Hydrochloride | quant. | 203–205 | 8.47 8.73 |
10.91 10.80 |
C$_{20}$H$_{22}$N$_2$·HCl | 8.57 | 10.85 | ||||||
| II$_b$ | $n$-CH$_3$C$_6$H$_4$ | Base | quant. | 114–115 | 0.50 (1 : 1) |
0.30 (4 : 1) |
C$_{20}$H$_{22}$N$_2$ | ||||||||
| II$_b$ | $n$-CH$_3$C$_6$H$_4$ | Picrate | quant. | 218–219 | 60.12 59.91 |
4.92 5.03 |
13.55 13.44 |
C$_{20}$H$_{20}$N$_2$·C$_6$H$_3$N$_3$O$_7$ | 60.12 | 4.85 | 13.48 | ||||
| II$_v$ | $n$-CH$_2$OC$_6$H$_4$ | Base | 81.2 | 149–150 | 0.20 (1 : 1) |
0.14 (4 : 1) |
C$_{20}$H$_{22}$N$_2$O$_2$ | ||||||||
| II$_v$ | $n$-CH$_2$OC$_6$H$_4$ | Picrate | 81.2 | 201–202 | 56.56 56.70 |
4.70 4.69 |
12.83 12.94 |
C$_{20}$H$_{22}$N$_2$O$_2$·C$_6$H$_3$N$_3$O$_7$ | 56.62 | 4.57 | 12.70 | ||||
| II$_g$ | $n$-C$_2$H$_5$OC$_6$H$_4$ | Base | 71.4 | 149–150 | 0.08 (1 : 1) |
0.16 (2 : 3) |
C$_{22}$H$_{26}$N$_2$O$_2$ | ||||||||
| II$_g$ | $n$-C$_2$H$_5$OC$_6$H$_4$ | Picrate | 71.4 | 199–199.5 | 58.19 58.21 |
5.01 4.98 |
11.85 12.01 |
C$_{22}$H$_{26}$N$_2$O$_2$·C$_6$H$_3$N$_3$O$_7$ | 58.01 | 5.04 | 12.08 | ||||
| II$_d$ | $n$-BrC$_6$H$_4$ | Hydrochloride | 96.2 | 200–201 | 47.34 47.26 |
4.16 3.95 |
6.21 6.10 |
C$_{18}$H$_{16}$N$_2$Br$_2$·HCl | 47.34 | 3.65 | 6.24 | ||||
| II$_d$ | $n$-BrC$_6$H$_4$ | Base | 96.2 | 164–165 | 0.70 (1 : 1) |
0.40 (9 : 1) |
C$_{18}$H$_{16}$N$_2$Br$_2$ | ||||||||
| II$_d$ | $n$-BrC$_6$H$_4$ | Picrate | 96.2 | 203–204 | 10.60 10.47 |
C$_{18}$H$_{16}$N$_2$Br$_2$·C$_6$H$_3$N$_3$O$_7$ | 10.79 | ||||||||
| II$_e$ | $n$-NO$_2$C$_6$H$_4$ | Hydrochloride | 90.2 | 201–203 | 55.62 55.66 |
4.46 4.35 |
14.51 14.62 |
C$_{18}$H$_{16}$N$_4$O$_4$·HCl | 55.62 | 4.41 | 14.41 | ||||
| II$_e$ | $n$-NO$_2$C$_6$H$_4$ | Base | 90.2 | 167–168 | 0.71 (1 : 1) |
0.82 (4 : 1) |
C$_{18}$H$_{16}$N$_4$O$_4$ | ||||||||
| II$_e$ | $n$-NO$_2$C$_6$H$_4$ | Picrate | 90.2 | 198–199 | 16.95 16.83 |
C$_{17}$H$_{16}$N$_4$O$_4$·C$_6$H$_3$N$_3$O$_7$ | 16.87 | — | |||||||
| II$_zh$ | $m$-NO$_2$C$_6$H$_4$ | Hydrochloride | 90.0 | 208–209 | 55.65 55.37 |
4.41 4.34 |
14.30 14.51 |
C$_{18}$H$_{16}$N$_4$O$_4$·HCl | 55.62 | 4.41 | 14.41 | ||||
| II$_zh$ | $m$-NO$_2$C$_6$H$_4$ | Base | 90.0 | 157–159 | 0.69 (1 : 1) |
0.80 (4 : 1) |
C$_{18}$H$_{16}$N$_4$O$_4$ | ||||||||
| II$_zh$ | $m$-NO$_2$C$_6$H$_4$ | Picrate | 90.0 | 187–188 | 16.93 17.02 |
C$_{18}$H$_{16}$N$_4$O$_4$·C$_6$H$_3$N$_3$O$_7$ | 49.57 | 3.29 | 16.87 | ||||||
| II$_z$ | $\alpha$-C$_{10}$H$_7$ | Base | 77.8 | 80–85 | 0.75 (1 : 1) |
0.95 (4 : 1) |
C$_{26}$H$_{22}$N$_2$ | ||||||||
| II$_z$ | $\alpha$-C$_{10}$H$_7$ | Picrate | 77.8 | 97–100 | 64.60 64.38 |
4.23 4.28 |
11.68 11.75 |
C$_{26}$H$_{22}$N$_2$·C$_6$H$_3$N$_3$O$_7$ | 64.95 | 4.26 | 11.84 | ||||
| II$_i$ | $n$-(C$_2$H$_5$)NC$_6$H$_4$ | Picrate | 186–188* | 60.40 60.28 |
6.33 6.33 |
15.51 15.33 |
C$_{26}$H$_{36}$N$_4$·C$_6$H$_3$N$_3$O$_7$ | 60.63 | 6.20 | 15.47 |
* Mixture of the main and by-product.
Table 2
By-products of Schiff bases of pyrrolines
| Ar | Derivatives | Yield,* % | m.p., °C | $R_f$, acetone : petr. ether | $R_f$, benzene : acetone | Found, % C | Found, % H | Found, % N | Empirical formula | Calculated, % C | Calculated, % H | Calculated, % N |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| $n$-CH$_3$C$_6$H$_4$ | Base | 3—5 | 129—130 | 0.80 (1 : 1) | 0.93 (4 : 1) | C$_{20}$H$_{22}$N$_2$ | ||||||
| $n$-CH$_3$C$_6$H$_4$ | Picrate | 229.5—230 | 60.00 | 5.18 | C$_{20}$H$_{22}$N$_2\cdot$C$_6$H$_3$N$_3$O$_7$ | 60.12 | 4.85 | |||||
| $n$-CH$_3$OC$_6$H$_4$ | Base | 10 | 176—177 | 0.68 (1 : 1) | 0.66 (4 : 1) | C$_{20}$H$_{22}$N$_2$O$_2$ | ||||||
| $n$-CH$_3$OC$_6$H$_4$ | Picrate | 162 | 56.79 56.78 |
4.42 4.57 |
C$_{20}$H$_{22}$N$_2$O$_2\cdot$C$_6$H$_3$N$_3$O$_7$ | 56.62 | 4.57 | |||||
| $n$-C$_2$H$_5$OC$_6$H$_4$ | Base | 18—20 | 148—149 | 0.59 (1 : 1) | 0.88 (2 : 3) | C$_{22}$H$_{26}$N$_2$O$_2$ | ||||||
| $n$-C$_2$H$_5$OC$_6$H$_4$ | Picrate | 154—155 | 57.95 57.88 |
5.10 5.13 |
12.08 12.06 |
C$_{22}$H$_{26}$N$_2$O$_2\cdot$C$_6$H$_3$N$_3$O$_7$ | 58.01 | 5.04 | 12.08 |
* Of the total amount of isolated mixture of ShOP.
Picrates of ShOP were obtained in ether, recrystallized from methanol or from aqueous methanol or ethanol solutions, and dried in vacuum over P$_2$O$_5$ with heating.
Hydrogenation of IIa. 7.8 g of IIa were dissolved in methanol, Raney Ni catalyst was added, and the mixture was hydrogenated in a duck-shaped vessel at room temperature until hydrogen absorption ceased (until the solution became decolorized). After hydrogenation was complete, the catalyst was filtered off, methanol was distilled off, the residue was diluted with water and steam-distilled. The distillate was extracted with ether, the ether extracts were dried over fused KOH, the ether was distilled off, and the residue was fractionated in vacuum. 1.05 g (38%) of aniline and 2.15 g (41.3%) of V were obtained. B.p. 130—131°/10 mm, $d_4^{20}$ 0.971, $n_D^{20}$ 1.5600, $MR_D$ 58.34, calculated 55.76.
Found, %: C 82.26, 82.01; H 9.81, 9.92; N 7.96, 8.04
C$_{12}$H$_{17}$N. Calculated, %: C 82.22; H 9.78; N 7.99
The residue after steam distillation was extracted with ether, the ether extracts were dried over fused KOH, the ether was distilled off, and the residue was distilled in vacuum. 2.30 g (28.9%) of IV was obtained. The oil is light yellow in color. B.p. 213—215°/4 mm. In the IR spectrum there are bands of the NH group in the region 3404—3409 cm$^{-1}$.
Found, %: C 81.20, 81.03; H 8.59, 8.53; N 10.68
C$_{18}$H$_{22}$N$_2$. Calculated, %: C 81.16; H 8.32; N 10.52
Benzoyl derivative—m.p. 128—129° (from isooctane).
Found, %: C 81.05, 80.99; H 7.21, 7.23; N 7.35
C$_{25}$H$_{26}$N$_2$O. Calculated, %: C 81.04; H 7.07; N 7.56
Moscow State University
named after M. V. Lomonosov
Received
5 IV 1965
REFERENCES
- M. A. Volodina, V. A. Kudryashova, A. P. Terent’ev, ZhOKh, 34, 3130 (1964).