Curtius rearrangement from acid chlorides

The Curtius rearrangement, like the Hofmann rearrangement, involve migration of an -R group from the G-O carbon atom to the neighboring nitro gen with simultaneous loss of a leaving group. The reaction takes place on heat ing an acyl azide that is itself prepared by nucleophilic acyl substitution of m acid chloride. 

Curtius rearrangement of the heteroaroyl azides, obtained from the reaction of the carboxylic acid chlorides with sodium azide, provides a route to the amino-pyrroles and -indoles (e.g. B-70MI30504, B-77MI30506, 78CPB1054), which, because of the ease of synthesis of the carboxylic acids, is frequently preferable to reduction of the nitro compounds. 

In both of these reactions, the product amine is formed from a carboxylic acid derivative precursor that has one more carbon than the amine. In the Hofmann rearrangement, the precursor is an amide, which is treated with Br2, NaOH and H2O. In the Curtius rearrangement, the precursor is an acid chloride, which is treated with NaN3, then with H2O and heat. 

Warren, J. D., Press, J. B. Trimethylsilylazide/KN3/18-crown-6. Formation and Curtius rearrangement of acyl azides from unreactive acid chlorides. Synth. Commun. 1980, 10, 107-110. 

Another interesting aspect is the elegant one-step synthesis of manifold substituted isocyanates achieved simultaneously by Washburne et al. and Kricheldorf who both used acyl chlorides acid anhydrides and esters to prepare isocyanates (457) via a Curtius rearrangement. This synthesis is especially useful since it enables for instance long chain isocyanates to be obtained (from fatty acid chlorides) and perfluorated compounds If a perfluoro-... 

The sodium azide pathway (Pathway A), Figure 4, begins with a thionylchloride treatment of the free acid to form the acyl chloride. Subsequent treatment with sodium azide may involve a non-aqueous environment (1,2-dimethoxy ethane, "dry method"), or an aqueous medium ("wet method"). The organic azide is recovered from the reaction mixture and converted into the isocyanate by the Curtius rearrangement. This may be accomplished in solid form ("dry method"), or in a non-aqueous solvent like dioxane or DMF ("solution method"). 

Applications of the Gassman oxindole synthesis in total synthesis are uncommon. Savall and McWhorter prepared a 6,7-dihydroxyindole derivative, part of the potent antihelmintic compound paraherquamide A, by using a chlorosulfonium ion (15) obtained from ethyl methylthioacetate and sulfuryl chloride.The intermediate oxindole 23 was obtained in 80% crude yield. The starting aniline was obtained in good yield from 2,3-dimethoxybenzoic acid via a modified Curtius rearrangement. Removal of the thiomethyl functionality with Raney nickel gave the final product in 62% yield. 

Scheme 9.129. A representation of the formation of phenyUsocyanate (CjHsNCO) from the reaction between the acid chloride of benzenecarboxyhc acid (benzoyl chloride, CeHsCOCl) and sodium azide (NaNs) followed by rearrangement of the benzoylazide (C6H5CON3) (the Curtius reaction). ...

Lactone 286 was transformed into aminomonocarba-disaccharide 288 using a five-step procedure involving the Curtius rearrangement of acyl azide 287 formed from the appropriate acid chloride (Scheme 3,43), ... 

Carboxylic acid chlorides may be converted to isocyanates via the Curtius rearrangement of the acyl azide. A solution of tetrabutylammo-nium azide (prepared by CH Cl extraction from aqueous sodium azide and tetrabutylammonium hydroxide) in toluene or benzene reacts readily with acid chlorides to give acyl azides. These are heated in solution to afford the isocyanates and nitrogen (Eq. 6.63) [101]. 

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