Addition elimination imino chloride

The pharmacological versatility of this general substitution strategy is further illustrated by diazonium coupling of 14 with 2-nitrobenzenediazonium chloride to produce biarylal-dehyde 18. Formation of the oxime with hydroxylamine is followed by dehydration to the nitrile. Reaction with anhydrous methanolic hydrogen chloride leads to imino ether and addition-elimination of ammonia leads to the antidepressant amid-ine, nitrafudam (20). ... 

The preparation of the A -desmethyl analogue, amoxapine (39-7), illustrates an alternate approach in which the oxygen ether linkage is formed last. Reaction of the imidazolide (39-2) from 2,4-dichlorobenzoic acid (39-1) and carbonyldiimidazole with ort/zo-aminophenol (39-3) gives the benzamide (39-4). This is then converted to its imino chloride (39-5) with the ubiquitous phosphorus oxychloride. Treatment of the product with piperazine leads to the amidine (39-6), probably by an addition-elimination sequence. Copper catalyzed displacement of chlorine by phenoxide closes the ring there is thus obtained amoxapine (39-7) [40]. 

Considerable effort has been expended in exploring the scope of ke-tenimine formation as it pertains to the introduction of 7(6)-methoxy substituents. Carrol et al. (1974) reported the facile construction of ke-tenimines derived from penicillin G and demonstrated deuterium incorporation at C-6 by base-catalyzed exchange of a related imino chloride. Workers at Sankyo later reported a method (Sugimura et al., 1976) by which an imine 145 was produced from an a-haloimino chloride (144) via base-catalyzed 1,4-elimination. The resulting imine was stereospe-cifically converted to methoxyketenimine 146 by the addition of meth-oxide anion (—78°C). Exposure to lithium methoxide at -20°C then led to iminoether 147, which was transformed to amide 148 by a new reaction with trimethylchlorosilane and I equiv of quinoline. 

Several papers report on the nucleophilic reactivity of dithiocarbamate ions towards alkyl halides, 1,2-dibromoalkyl compounds, alkyl and aryl chloroformates, chloroacetic acid, chloroacetates, 3-halo-genophthalides, sulphenyl chlorides, sultones, and trialkylam-monium compounds. Examples of a similar reactivity of dithiocarbazate anions have also appeared. " A series of papers deal with addition or addition-elimination reactions of dithiocarbamate - or dithiocarbazate anions with w-nitrostyrene, 2-thioxo-, 2-oxo-, and 2-imino-5-methoxycarbonylmethylidene-4-thiazolidones, dimethyl acetylenedicar-boxylate, and NN -dialkyl phenylpropiolamidines. S-Monoalkylated N-cyanodithioimidocarbonates (492) underwent oxidative ring-closure to give 3-halogeno-l,2,4-thiadiazole sulphides (493) on treatment with halogenating agents. ... 

Analogous metal complexes (60) and (61) have been obtained from reactions of the orr/io-metalated species (59) and the metal chlorides FeCb and InCb, respectively. Elimination of LiCl leads to the formation of a- metal carbon bonds, whereas additional metal coordination is provided by imino nitrogens. For complex (62) only a- metal carbon bonds are operative. The lengthening of the N(M)P bond lengths in (60) and (61) in comparison to the others in (61) and (62) (see Section 5) can be ascribed to the imino N-metal bonding. ... 

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