Thionyl chloride with nitro compounds

Activated compounds such as 5-nitropyrimidin-2-one and 1-methyl-5-nitro-2-pyridone form the 2-chloro analogs with thionyl chloride 223b. 312b displacement of the —O—SO—Cl group. In reactions... 

An unsuccessful attempt to repeat this reaction was made by Bird however, he was able to show that dibenzothiophene 5-oxide did, in fact, react with either thionyl chloride or phosphorus oxychloride to yield 2-chlorodibenzothiophene in good yield. Since all methods of nitration of dibenzothiophene yield a mixture of 2-nitrodibenzothio-phene and dibenzothiophene 5-oxide, which have identical melting points, it was concluded that the earlier workers had in fact been working with the sulfoxide and not the nitro compound. The reaction was rationalized as being a deoxygenative halogenation of a heterocyclic 5-oxide akin to the Meisenheimer reaction of A-oxides, which already had precedents in the sulfoxide field. Unfortunately the 2-chlorodibenzothiophene prepared by this route is contaminated with 2,8-dichlorodibenzothiophene which cannot be removed by crystallization. The best method of preparation of this compound is therefore via a Sandmeyer reaction on 2-aminodibenzothiophene. ... 

Several reactive chloro compounds have been used to attempt to effect the controlled monochlorination of aromatic amines. One such reagent is N-chlorosuccinimide, with which the chlorination of aniline, for example, can be largely restricted to monosubstitution, although a mixture of isomers (orthopara, 1.9 1) is obtained.24 One approach to the achievement of specific ortho chlorination is illustrated by the synthesis of o-chlorobenzanilide (Expt 6.61), readily hydrolysable to o-chloroaniline. The anilide is formed, by a type of Swi mechanism indicated below, when AT-phenylhydroxylamine is benzoylated and the product is treated with thionyl chloride.25 The reaction has been successfully applied to several substituted JV-phenylhydroxylamines, prepared by the controlled reduction of the corresponding substituted nitro compounds (cf. Expt 6.87). 

Melphalan and the racemic analog have been prepared by two general routes (Scheme I). In Approach (A) the amino acid function is protected, and the nitrogen mustard moiety is prepared by conventional methods from aromatic nitro-derivatives. Thus, the ethyl ester of N-phthaloyl-phenylalanine was nitrated and reduced catalytically to amine I. Compound I was reacted with ethylene oxide to form the corresponding bis(2-hydroxyethyl)amino derivative II, which was then treated with phosphorus oxychloride or thionyl chloride. The blocking groups were removed by acidic hydrolysis. Melphalan was precipitated by addition of sodium acetate and was recrystallized from methanol. No racemization was detected [10,28—30]. The hydrochloride was obtained in pure form from the final hydrolysis mixture by partial neutralization to pH 0.5 [31]. Variants of this approach, used for the preparation of the racemic compound, followed the same route via the a-acylamino-a-p-aminobenzyl malonic ester III [10,28—30,32,33] or the hydantoin IV [12]. 

The direct dehydration of aliphatic y3-nitro alcohols to nitro olefins is usually unsatisfactory. The latter compounds are obtained by method 24 or by treating the nitro alcohols with thionyl chloride and pyridine, ... 

Synthesis of the benzo[l,2-c 3,4-c ]bis[l,2,5]thiadiazole (509) required cyclization of diamine (508). Nitration of (505) led to 4-nitro-2,1,3-benzothiadiazole (506) in 95% yield. Amination of (506) with hydroxylamine in basic medium led to compound (507), immediately reduced to the diamino derivative (508). Ring closure of (508) with thionyl chloride and pyridine led to the benzo[l,2-c 3,4-c ]bis[l,2,5]thiadiazole (509) in 89% yield. Compound (509) has been successfully used in the synthesis of several fused tetracyclic compounds (Scheme 40) <75JHC829>. 

The nitro compound is also an ester which can be derived from an alcohol and an acid derivative. In this case, it would be best to synthesize the ester from the acid chloride, p-chlorobenzoyl chloride, and the amino alcohol in the presence of base. The base will prevent protonation of the amino group by the subsequently formed HCl. The nitro group can be given its proper para orientation by directly nitrating toluene. Subsequent oxidation of the methyl group and treatment with thionyl chloride will yield the acid chloride. The alcohol portion of the ester can be derived from the reaction of diethylamine with ethylene oxide. Thus, the synthetic scheme would be... 

The most appropriate technical synthesis of triazoxide [60], as described in Scheme 21.5, starts with phosgenation of 2-nitro-4-chloroaniline, followed by am-monolysis of the isocyanate. Cyclization of the formed arylurea occurs by treatment with aqueous sodium hydroxide to obtain the sodium salt of 3-hydroxy-7-chloro-l,2,4-benzotriazine-l-oxide. After acidification, the hydroxy group can be converted into the corresponding imidazolyl derivative after being transformed into the chloro compound with thionyl chloride. 

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