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New instances of nuclear chlorination of benzene derivatives by the action of cold aqueous sodium hypochlorite are reported. The reaction gives good yields of monochloro derivatives when the orientation is favourable.
It is known that certain cyclic compounds can be halogenated by the action of aqueous hypohalites. Chlorination of benzoic acid by aqueous sodium hypochlorite was studied by Smith12. He obtained a mixture of the three isomeric monochlorobenzoic acids as well as some dichloro acid. Salicylic acid undergoes chlorination in the same way. yielding a mixture from which some monochloro-salicylic acid can be isolated4.
Table I
Chlorination Products
| Starting material | Moles NaOCl |
Product |
Yield |
mp°C* |
Ref |
| Anisic acid | 2 |
3-chloro |
80% |
215 |
|
| Vanillic acid | 2 |
5-chloro |
85% |
242-244 |
|
| p-Hydroxybenzoic acid | 2 |
3,5-dichloro |
50% |
256-258 |
|
| m-Methoxybenzoic acid | 2 |
6-chloro |
60% |
170-171 |
|
| 2-OH-4-AcO-benzoic acid | 2 |
5-chloro |
40% |
176-177 |
|
| Piperonylacetic acid | 2 |
6-chloro |
80% |
177-178 |
|
| Anisylacetic acid | 1 |
3-chloro |
50% |
94-95 |
|
| Vanillin | 1.5 |
5-chloro |
90% |
164-165 |
|
| Piperonal | 1/2 |
6-chloro |
poor |
106-110 |
|
| 2,4-Dihydroxybenzaldehyde | 1.3 |
5-chloro |
80% |
156-157 |
|
| Phenoxyacetic acid | 4 |
2,4-dichloro |
75% |
138-139 |
|
| 2-Chlorophenoxyacetic acid | 2 |
2,4-dichloro |
80% |
138-139 |
|
| 2-Methylphenoxyacetic acid | 1 |
4-chloro |
85% |
118-119 |
* Melting points (of recrystallized product) are not corrected.
Nuclear chlorinated products have been prepared in the present work from various substituted benzoic acids, arylacetic acids, aryloxyacetic acids and arylaldehydes. using sodium hypochlorite as the reagent. The results indicate that this method of halogenation is more widely applicable than previously supposed.
The procedure is extremely simple. The substance is dissolved or suspended in dilute alkali and mixed with sodium hypochlorite solution. It is left for an hour at ordinary temperature with occasional stirring. The product is then removed.
Certain substances, in which the orientation is most favourable, give monochloro derivatives in almost theoretical yield. These include vanillin, anisic acid, and piperonylacetic acid. The position taken up by halogen is the same as in ordinary non-aqueous chlorination. There is apparently no oxidation of the aldehyde group in the reaction with vanillin.
A solution containing one mole of sodium hypochlorite per litre was prepared as the reagent6. A suspension of calcium hypochlorite may be used but gives slightly lower yields. The general method of chlorination is illustrated by the reaction of sodium hypochlorite solution with anisic acid as follows:
Anisic acid (3.8 gm., 1/40 mole) was dissolved in 150 mL of water and 25 mL of 4% sodium hydroxide solution. It was cooled to 20°C., and mixed with 50 mL (1/20 mole) of sodium hypochlorite solution. The temperature was maintained at 20° C. for one hour with occasional stirring. Upon acidifying, a precipitate of almost pure 3-chloroanisic acid was obtained. The yield was 3.9 gm. (80% of theory). After one crystallization from toluene it melted at 215°C.
The experiments are summarized in Table I.
5-Chlorovanillic acid
This product was also made by chlorinating vanillic acid in chloroform by gaseous chlorine. It is considered to be 5-chlorovanillic acid since bromination by the same procedure is known to give 5-bromovanillic acid. The melting point agrees with that given by Raiford and Potter10 for 5-chlorovanillic acid prepared from 5-chlorovanillin. The substance is readily soluble in ethanol and ether, slightly soluble in toluene and insoluble in chloroform and hexane.
Chlorination of p-hydroxybenzoic acid
A monochloro derivative could not readily be isolated.
2-Hydroxy-4-acetoxy-5-chlorobenzoic acid
β-Resorcylic acid itself did not react normally with sodium hypochlorite, but monoacetyl-β-resorcylic acid gave the monochloro derivative without difficulty. mp 176-177°C. This substance has not been reported hitherto. Upon hydrolysis, it yielded 2,4-dihydroxy-5-chlorobenzoic acid, mp 218°C11.
6-Chloropiperonylacetic acid
It did not depress the melting point of an authentic sample prepared by the method of Naik and Wheeler8. The substance is readily soluble in alcohol, ether, and acetic acid, and is moderately soluble in benzene and chloroform. It is insoluble in hexane.
5-Chlorovanillin
This substance was identified by mixed melting point with an authentic sample prepared by the method of Raiford and Lichty9. It crystallizes from water in small plates. It is soluble in alcohol, moderately soluble in benzene, and sparingly soluble in water.
6-Chloropiperonal
Piperonal gave a mixture of chlorinated products from which 6-chloropiperonal was isolated in poor yield, mp 106-110°C.
5-Chloro-2,4-dihydroxybenzaldehyde
This product is evidently the monochloro derivative prepared by Gattermann3, mp 157°C. The position of the chlorine group was established by Chakravarti and Ghosh1.