Full Text
Chemistry
N. S. Kozlov and I. A. Shur
Catalytic Synthesis of 4-Methyl-2-phenyl-5,6-benzoquinoline and 2,4-Diphenyl-5,6-benzoquinoline and Their Derivatives
(Presented by Academician A. A. Balandin, 14 VI 1958)
As is known, the synthesis of 5,6-benzoquinoline and its derivatives is carried out by the usual methods for the synthesis of quinoline compounds \((^1)\). Among the known methods, the most convenient way to obtain 2-phenyl-5,6-benzoquinoline and its derivatives is the Debner method \((^{2,3})\), which is based on the condensation reaction of 2-naphthylamine and various aromatic aldehydes with pyruvic acid. The 2-phenyl-5,6-benzoquinoline-4-carboxylic acid formed in this reaction and its derivatives, on heating, are readily decarboxylated, being converted into 2-phenyl-5,6-benzoquinoline and its derivatives.
However, the Debner method cannot be regarded as perfect, since the synthesis of the quinoline base is carried out in two stages, which complicates the reaction and lowers the yield of the final products.
Recently, a new method has been developed for the synthesis of 2-phenyl-5,6-benzoquinoline and its derivatives by catalytic condensation of 2-naphthylamine and various aromatic aldehydes with acetylene \((^{4,5})\).
It should be noted that the synthesis of 4-methyl-2-phenyl-5,6-benzoquinoline and 2,4-diphenyl-5,6-benzoquinoline and their derivatives has been developed quite insufficiently \((^1)\). We know only the works of John and Nazick \((^6)\), who, by heating benzalacetone and 2-naphthylamine in a sealed tube, obtained 4-methyl-2-phenyl-5,6-benzoquinoline in low yield, and the work of Dzevonsky \((^7)\), who carried out the synthesis of 2,4-diphenyl-5,6-benzoquinoline by condensation of 1-benzoyl-2-aminonaphthalene with acetophenone.
It is known that the 5,6-benzoquinoline nucleus is part of physiologically active ergot alkaloids and of other plants. In this connection, it may be assumed that a number of 5,6-benzoquinoline derivatives should also possess bactericidal properties. Therefore the development of new methods for the synthesis of 4-methyl-2-phenyl-5,6-benzoquinoline and 2,4-diphenyl-5,6-benzoquinoline and their derivatives should be of scientific and practical interest.
In setting up the present work, we were guided by theoretical considerations that had been set forth earlier by one of us \((^8)\). We assumed that Schiff bases, under appropriate conditions, should condense with acetone and acetophenone, forming beta-arylaminoketones as intermediate products, which after cyclization should be converted into diphenyl derivatives of quinoline. This reaction should proceed especially readily with the products of the interaction of acetophenone with Schiff bases obtained from 2-naphthylamine and aromatic aldehydes, in view of the exceptional ability of compounds of this type to cyclize in the alpha position of the naphthalene nucleus \((^1)\).
The experiments carried out by us confirmed the correctness of these ideas. Indeed, under appropriate conditions Schiff bases from 2-naphthylamine and aromatic aldehydes—benzaldehyde, o-, m- and p-nitrobenzaldehydes, p-dimethylaminobenzaldehyde—enter into reaction
Table 1
| Substance and its empirical formula | Melting point, °C: obtained | Melting point, °C: lit. data | Melting point, °C: hydrochloride salt | Melting point, °C: picrate | Product yield, % | N, %: calcd. | N, %: found | N, %: found | Pt-platinates, %: calcd. | Pt-platinates, %: found |
|---|---|---|---|---|---|---|---|---|---|---|
| 4-Methyl-2-phenyl-5,6-benzoquinoline, C$_{20}$H$_{15}$N | 152—155 | 152 | 265 | 224 | 41,2 | 5,21 | 5,25 | 5,03 | 20,16 | 20,27 |
| 4-Methyl-2-(4-methoxyphenyl)-5,6-benzoquinoline, C$_{21}$H$_{17}$NO | 124 | — | 240 | 225 with decomp. | 20,0 | 4,53 | 4,79 | 4,81 | 19,56 | 19,58 |
| 4-Methyl-2-piperonyl-5,6-benzoquinoline, C$_{21}$H$_{15}$NO$_2$ | 161—162 | — | 275 | 203 with decomp. | 23,5 | 4,47 | 4,24 | 4,53 | 18,84 | 19,04 |
| 4-Methyl-2-(3-nitrophenyl)-5,6-benzoquinoline, C$_{20}$H$_{14}$N$_2$O$_2$ | 178 | — | 231—233 | 220 | 47,4 | 8,92 | 9,23 | 9,13 | 18,80 | 18,53 |
| 4-Methyl-2-(4-nitrophenyl)-5,6-benzoquinoline, C$_{20}$H$_{14}$N$_2$O$_2$ | 192 | — | 237—238 | 228 | 34,4 | 8,92 | 8,75 | 8,89 | 18,80 | 18,63 |
| 2,4-Diphenyl-5,6-benzoquinoline, C$_{25}$H$_{17}$N | 144—145 | 144 | 231 | 40,0 | 4,23 | 4,22 | 4,25 | 18,20 | 18,50 | |
| 2-(4-Methoxyphenyl)-4-phenyl-5,6-benzoquinoline, C$_{26}$H$_{19}$NO | 154—155 | — | 210 | 235 with decomp. | 32,5 | 3,88 | 3,70 | 3,78 | 17,24 | 17,50 |
| 2-(3-Nitrophenyl)-4-phenyl-5,6-benzoquinoline, C$_{25}$H$_{16}$N$_2$O$_2$ | 231 | — | 226 | 204 | 50,0 | 7,45 | 7,51 | 7,72 | 16,79 | 16,88 |
| 2-(4-Nitrophenyl)-4-phenyl-5,6-benzoquinoline, C$_{25}$H$_{16}$N$_2$O$_2$ | 254 | — | 252 | 218—220 | 40,5 | 7,45 | 7,42 | 7,57 | 16,79 | 16,80 |
| 2-(4-Dimethylaminophenyl)-4-phenyl-5,6-benzoquinoline, C$_{27}$H$_{22}$N$_2$ | 180 | — | decomp. | decomp. | 42,0 | 7,43 | 7,43 | 7,53 | — | — |
with acetone and acetophenone, forming 2,4-diphenyl-5,6-benzoquinoline and 4-methyl-2-phenyl-5,6-benzoquinoline and their p-methoxy, p-dimethylamino-, and m- and p-nitro derivatives. Most of these compounds were obtained by us for the first time. As the active catalyst in this reaction we used 2-naphthylamine hydrochloride.
The mechanism of these reactions may be expressed by the following equation:
\[ \begin{gathered} \text{[structural scheme]} \\ \ce{N=CH-C6H4R} \quad \xrightarrow[\ce{CH3-CO-R'}]{} \quad \ce{NH-CH-C6H4R} \quad \xrightarrow{} \quad \text{[benzoquinoline structure]} + \ce{H2O} + \ce{H2}, \end{gathered} \]
where
\[ \begin{aligned} R &= \ce{H-};\ p\text{-}\ce{CH3O-};\ m\text{- and }p\text{-}\ce{NO2};\ p\text{-}\ce{(CH3)2N-};\\ R' &= \ce{CH3};\ \ce{C6H5};\ p\text{-}\ce{CH3O-C6H4};\ m\text{-},\ p\text{-}\ce{NO2-C6H4}. \end{aligned} \]
The reaction mechanism indicated above was confirmed experimentally by specially designed experiments. For this purpose we developed a new variant of the synthesis of beta-2-naphthylamino-beta-phenylpropiophenone, which was subjected to cyclization into 1,3-diphenyl-5,6-benzoquinoline.
Description of the Method
The synthesis of 4-methyl-2-phenyl-5,6-benzoquinoline and its derivatives was carried out as follows. A reaction mixture consisting of 0.05 g-mol of Schiff base, 0.05 g-mol of acetone, 10–20 ml of alcohol, and 1.0 g of 2-naphthylamine hydrochloride is heated on a water bath for 15–30 min. After cooling, the precipitate that separates is filtered off, treated with aqueous ammonia, and crystallized from alcohol and toluene.
To obtain 2,4-diphenyl-5,6-benzoquinoline and its derivatives, a reaction mixture consisting of 0.05 g-mol of Schiff base, 0.05 g-mol of acetophenone, and 1.0 g of 2-naphthylamine hydrochloride, without solvent, is heated to 160–180° for 15 min. The subsequent workup is carried out as in the preceding case. The results obtained by us and the constants of the substances synthesized by us are given in Table 1.
Thus, in the present work we succeeded in developing a new, highly accessible and convenient method for the synthesis of 4-methyl-2-phenyl-5,6-benzoquinoline and 2,4-diphenyl-5,6-benzoquinoline and their derivatives, and in synthesizing ten compounds of this series, eight of which had not previously been described. It is quite clear that the introduction into this reaction of other Schiff bases and the replacement of acetone and acetophenone by other ketones opens new routes to the synthesis of varied and numerous derivatives of 5,6-benzoquinoline.
Perm Agricultural Institute
Received
24 IV 1958
CITED LITERATURE
- R. Elderfield, Heterocyclic Compounds, IL, 4, 1955, p. 476.
- O. Döbner, Ber., 27, 352 (1894).
- O. Döbner, P. Kuntze, Lieb. Ann., 249, 109 (1888).
- N. S. Kozlov, O. K. Kozminykh, ZhOKh, 27, 1628, 3122 (1957).
- N. S. Kozlov, O. K. Kozminykh, DAN, 114, No. 4, 785 (1957).
- H. John, Fr. Hoziczka, J. prakt. Chem., (2), 111, 65 (1925).
- K. Dziewonski, L. Kwiecinski et al., Bull. Intern. Acad. Polon., cl. sci. math. nat. A., 329 (1934); Chem. Abstr., 29, 1084 (1935).
- N. S. Kozlov, ZhOKh, 7, 1860 (1938).
- R. Ciusa, L. Musaja, Gazz. Chem. Ital., 69, 796 (1929).
- E. A. Robinson, M. T. Bogert, J. Org. Chem., 1, 65 (1936).