Dehydrochlorination, acid chlorides

Phthalic anhydride is reacted with phenylacetic acid to form 3-benzylidenephthalide which is then hydrogenated to 2-phenethylbenzoic acid. Conversion to the acid chloride followed by intramolecular dehydrochlorination yields the ketone, 5H-dibenzo[a,d] cyclohepten-5-one. The ketone undergoes a Grignard reaction with 3-(dimethylamino)propyl chloride to give 5-(7-dimethylaminopropylidene)-5H-dibenzo[a,d] cycloheptene. 

Arylsydnone-4-carbonitrile oxides, which are generated in situ by thermal dehydrochlorination of the corresponding hydroximic acid chlorides, undergo 1,3-dipolar cycloadditions with sydnone-4-carbonitriles to give 3-aryl-4-[5-(3-arylsydnonyl)-l,2,4-oxadiazol-3- yl]sydnones 228 (392). 

Intramolecular [2 + 2]cycloadditions benzofurans. On dehydrochlorination with triethylamine in refluxing C6H6, these acid chlorides are converted into (o-acylphenoxy)ketenes, which undergo a [2 + 2]cycloaddition reaction to form p-lactones, which are converted to benzofurans by spontaneous decarboxylation in 53-82% yield.1... 

Chlorination of aldoximes. NCS converts aryl aldoximes to hydroxamic acid chlorides without significant chlorination of the aryl group. This reaction has been used for a novel synthesis of nitrile oxides. Thus reaction of salicylaldoxime (1) with NCS followed by dehydrochlorination with pyridine generates a nitrile oxide, which is trapped by styrene to give the isoxazoline 2. The N-O bond can be cleaved by catalytic hydrogenation to 3, which is converted into the chalcone 4 on elimination of water. This product can be converted by classical methods to the flavanone 5 and the flavone 6. An analogous route can be used to synthesize 2-... 

Other acid chlorides of the type RCH2COCl can be similarly dehydrochlorinated. For example, caproyl chloride (1.2 moles) was converted into di-w-amyl ketone, b.p. 98-102°/15 mm., in 60-71.5% yield. In this case, it was found preferable to remove the amine salt from the reaction mixture by washing with 2% sulfuric acid. The butylketene dimer was then extracted from the reaction mixture by washing with 5% sodium hydroxide solution the alkaline solution was acidified with sulfuric acid and steam-distilled. The oily layer in the distillate was separated and fractionated. 

The submitters have shown that these reactions proceed by dehydrochlorination of the acid chloride to the ketene, which is then trapped by... 

Dehydrobromination, of 2 bromo-dodecanoic acid, 37, 29 of 10,11-dibromohendecanoic acid with sodium amide, 32, 104 of 9,10-dibromooctadecanoic acid with sodium amide, 37, 77 Dehydrochlorination, of acid chlorides,... 

The formation of ferf-butyl ester 54 may be rationalized by N-chlorination of the pyrazolidinone 50 to give N-chloropyrazolidinone 51. 1,4-Dehydrochlorination of intermediate 51 involving ring-opening by bond breaking steps a (steps a alone would lead to acid chloride 52) and concomitant deprotonation h generates the ketene intermediate 53. Addition of the previously formed ferf-butyl alcohol to ketene 53 provides the otherwise not readily available ferf-butyl ester 54 (87%). 

Dehydrochlorination of acid chlorides of type RCH2COCI by proton sponge 1 in order to produce monoketenes is not directly realized232,233, but proceeds in the presence of benzoylquinine (BQ) as a shuttle base . The in situ generated ketenes were used further for the synthesis of optically active /3-lactams 258 (Scheme 48). Additionally, a method providing fraws-isomers of 258 with the help of diamine 1 has recently been elaborated234. 

In a flow system, at 200-250 C, phosgene combines with ethene over activated charcoal to give 1,2-dichloroethane, with an activation energy calculated to be 29.6 kj mol [1CI88,ICI89,ICI90]. A small quantity of chloroethene is formed at temperatures as low as 100 C from the simultaneous decarbonylation and dehydrochlorination of the intermediate acid chloride [ICI90] ... 

A related [4 + 4] annulation strategy relies on the base-promoted 1,4-dehydrochlorination of a,P-un-saturated acid chlorides the transformation outlined in Scheme 29 (reported by Dreiding and cowor-kers) illustrates this approach. In some cases it is possible to effect all thiee steps — ketene generation, [2 + 2] cycloaddition, and Cope reanangement — in a single synthetic operation. ... 

Esterification of tropic acid with acetyl chloride gives tropic acid acetate which on chlorination with thionyl chloride yields the corresponding acid chloride. The resulting product on treatment with 4-((ethylamino) methyl-pyridine and subsequently with an appropriate dehydrochlorinating agent gives rise to tropicamide acetate. Saponification of this compound affords the desired official product. 

This dehydrochlorination occurs readily in the presence of a tertiary amine, such as triethylamine, and the reaction is similar to the dehydrochlorination of carboxylic acid chlorides to ketenes However, in the dehydrochlorination of the N-allylimidoyl chloride (CLXIX) with triethylamine, rearrangement to the nitrile CLXX occurs... 

Addition of chlorine to the exomethylene moiety in (48) under irradiation followed by dehydrochlorination with DBN gave 3-chloromethyH-oxacephem (75) in 86% yield. Methoxylation of (75), as reported in the previous section, was followed by a substitution reaction at the C-3 position with heterocyclic thiolates, to obtain 3-heterocyclicthiomethyl derivatives (76) in about 90% yield. The side-chain cleavage by the conventional method proceeded with little epimerization at C-7 giving exclusively the 7a-methoxy-7p-amino-l-oxacephem nucleus (77). Acylation with an appropriate acid chloride followed by deprotection with aluminum chloride or stannic chloride in anisole [32] afforded the representative oxacephem antibiotics, latamoxef (11a) [15], flomoxef (11b) [16] and 2355-S (11c) [17] in high yields. 

Leckta et al. recently described an efficient procedure for the in situ generation of reactive monosubstituted ketenes through dehydrochlorination of acid chlorides promoted by NaH/15C5 in THE. This new methodology was applied to a cost-effective, catalytic asymmetric synthesis of P-lactams and a-chloroesters, pharmaceutically useful classes of compounds (Eq. 18). 

Trifluoroacetonitrile AT-oxide, generated in situ by dehydrochlorination of the corresponding hydroxamic acid chloride with triethylamine, has been trapped with several dipolarophiles (see Scheme 22) it failed to attack perfluorobutyronitrile, in contrast to benzonitrile JV-oxide (see Scheme 23), and apparently gave unidentified high-boiling material rather than a furoxan in the absence of a suitable dipolarophile. Trifluoromethyltetrazolato-complexes prepared via 1,3-dipolar cycloadditions between trifluoroacetonitrile and azido-complexes of Group IB metals (e.g. see Scheme 24) have received attention (seep. 349). ... 

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