Oxalyl Chloride reactions with carbonyl groups

Reactions with Carbonyl Groups. Unsaturated 3-keto steroids give the corresponding 3-chloro derivatives with oxalyl chloride (eq 18). Prolonged heating can give rise to... 

These cyclizations normally involve a carbonyl group. The enamine 109 undergoes a reaction with oxalyl chloride to give an intermediate product 110, which is then cyclized upon treatment with HC1 leading to the angular tricyclic compound 111 in excellent yield (Scheme 11) <1995EJM525>. 

The energetic 1,3,4-oxadiazole (22) is synthesized from the reaction of the tetrazole (20) with oxalyl chloride. In this reaction the tetrazole (20) undergoes a reverse cycloaddition with the expulsion of nitrogen and the formation of the 1,3-dipolar diazoalkane (21) which reacts with the carbonyl groups of oxalyl chloride to form the 1,3,4-oxadiazole rings. 

The reaction sequence proposed in Scheme 12 is consistent with the approach of the reagent from the least hindered a-face of the penicillanate and interaction of the diazo-group predominantly with the re-face of one of the carbonyl groups of the oxalyl chloride thus, resulting in the formation of spiro product 43, 44 by displacement of nitrogen. 

Acylation of the C3 position can also be accomplished with acid chlorides, as illustrated in the synthesis of indole 7.34, a drug for the treatment of depression. Reaction of indole 7.31 with oxalyl chloride affords C3-substituted product 7.32 even though the benzene ring is very electron-rich. Conversion to amide 7.33 is followed by reduction with lithium aluminium hydride which removes both carbonyl groups, affording the target indole 7.34. 

COOH — —CHO. This conversion can be effected in one flask by treatment of the carboxylic acid with N,N dimethylchloromethyleniminium chloride (prepared from DMF and oxalyl chloride) and pyridine to form a betaine, which is then reduced to the aldehyde by the hydride in the presence of a catalytic amount of Cul at — 78° The reaction is applicable to aliphatic and aromatic acids, and can tolerate halo, cyano, ester, and even carbonyl groups. Yields are usually —65-80%. 

Removal of the ester Et group with Me SiBr, followed by treatment of the product (112 d) with oxalyl chloride led to the cyclic phosphonic chloride (112 e) as stereoisomeric mixture further reaction with PhSH under basic conditions gave (112 f), also as a mixture of stereoisomers. The (2 ) form of (112 f) reacted with vinylmagnesium bromide to give the 2-vinyl derivative, a step which failed, however, with the (2B) epimer. Attempts to oxidatively cleave the vinyl group and so generate a compound having a carbonyl... 

The additional carbon atom required for building the five-membered ring D is then added by means of methyl-magnesium bromide (16-4). The ester at future C15 is reduced to a carbinol by reaction with lithium aluminum hydride. Swern oxidation (dimethyl sulfoxide and oxalyl chloride) next serves to oxidize each of the two resulting hydroxyl groups to carbonyl functions (16-5). Dieckmann-like base-catalyzed condensation then closes the five-membered ring... 

In spite of the usefulness of these complexes, it is generally not possible to cause the satisfactory reaction with transition metals in the metallic state [86] under mild conditions due to their poor reactivity. We have reported that activated metallic nickel, prepared by the reduction of nickel halide with lithium, underwent oxidative addition of benzylic halides to give homocoupled products [45]. We reported that carbonylation of the oxidative adducts of benzylic halides to the nickel proceeded smoothly to afford symmetrical 1,3-diarylpro-pan-2-ones in moderate yields, in which the carbonyl groups of alkyl oxalyl chlorides served as a source of carbon monoxide [43] see Equation 7.5. 

A very useful group of procedures for oxidation of alcohols to ketones have been developed that involve dimethyl sulfoxide (DMSO) and any one of a number of electrophilic molecules, particularly dicyclohexylcarbodiimide, acetic anhydride, trifluoroacetic anhydride, oxalyl chloride, and sulfur trioxide. The initial work involved the DMSO-dicyclohexylcarbodiimide system.The utility of the method has been greatest in the oxidation of molecules that are highly sensitive to more powerful oxidants and therefore cannot tolerate alternative methods. The mechanism of the oxidation involves formation of intermediate A by nucleophilic attack of DMSO on the carbodiimide, followed by reaction of this species with the alcohol. A major part of the driving force for the reaction is derived from the conversion of the carbodiimide to a urea, with formation of an amide carbonyl. ... 

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