Curtius rearrangement, preparation

In these cases the acyl azides formed have been used to prepare amines via Curtius rearrangement. The acyl chloride or azide intermediates can. however, also be reacted with amines or alcohols to form amides or esters. 

The Curtius rearrangement in acetic anhydride of the azide (8) prepared from 4-carboxythiazole yields 4-acetamidothiazole (Scheme 8) (47). The same reaction starting with ethyl-2-methyl-4-thiazolyl carboxy-late, failed to give the 4-aminothiazole (48). Heterocyclizations are more convenient synthetic methods (Chapter II. Table 40). 

The preparation and properties of these tertiary aminimides, as weU as suggested uses as adhesives (qv), antistatic agents (qv), photographic products, surface coatings, and pharmaceuticals, have been reviewed (76). Thermolysis of aminimides causes N—N bond mpture foUowed by a Curtius rearrangement of the transient nitrene (17) intermediate to the corresponding isocyanate ... 

A third approach to 3-amino-/3-lactams is by Curtius rearrangement of the corresponding acyl azides. These are readily prepared from r-butyl carbazides, available via photochemical ring contraction of 3-diazopyrrolidine-2,4-diones in the presence of f-butyl carbazate (c/. Section 5.09.3.3.2). Thus treatment of (201) with trifluoroacetic acid followed by diazotiz-ation gives the acyl azide (202) which, in thermolysis in benzene and subsequent interception of the resulting isocyanate with r-butanol, yields the protected 3-amino-/3-lactam (203) (73JCS(P1)2907). 

The Hofmann and Curtius rearrangements have been applied to 2-thienylacryl amides for the preparation of 2-thiophene acetaldehydes. The Hofmann rearrangement proceeds also with 3-thenamides but fails with 2-thenamide. ... 

The Curtius rearrangement can be catalyzed by Lewis acids or protic acids, but good yields are often obtained also without a catalyst. From reaction in an inert solvent (e.g. benzene, chloroform) in the absence of water, the isocyanate can be isolated, while in aqueous solution the amine is formed. Highly reactive acyl azides may suffer loss of nitrogen and rearrange already during preparation in aqueous solution. The isocyanate then cannot be isolated because it immediately reacts with water to yield the corresponding amine. 

The Curtius rearrangement is a useful method for the preparation of isocyanates as well as of products derived thereof. The substituent R can be alkyl, cycloalkyl, aryl, a heterocyclic or unsaturated group most functional groups do not interfere. 

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. 

How would you prepare o-methvlbenzylamine from a carboxylic acid, using both Hofmann and Curtius rearrangements ... 

The Curtius rearrangement procedure described here is a modification of one reported by Winestock. The submitters have found this procedure to be considerably more reproducible when N,N-diisopropylethylamine is substituted for triethylamine. The procedure described for the preparation of trans-2,4-pentadienoic acid is a modification of an earlier one by Doebner. The submitters have found this method to give reproducibly higher yields, and to be more convenient, than other commonly used procedures for preparing this material. The use of dichloromethane as the extracting and crystallizing solvent greatly simplifies the isolation of polymer-free samples of the crystalline acid. 

Employing this method, enantioenriched phenol esters 68, amides 69, and carbamates 70 (after Curtius rearrangement of the intermediate acyl azide) were prepared in yields often greater than 90% with ee-values reaching up to 97% (generally 80-95%, see Fig. 37). 

Another examination involves a synthesis of thienobenzazepines based on the formation of key intermediate 6 prepared according to the method of McDowell and Wisowaty (Scheme 6.2). ° Selective reduction of this intermediate using zinc dust in 28-30% ammonia solution afforded the benzoic acid 7, which upon subsequent Curtius rearrangement and aluminum trichloride-mediated cyclization furnished the oxo-azepine 8. While this synthetic approach gave the tricycle in a few synthetic transformations, many of the same concerns as above exist when considering large scale preparation of 8 the use of large amounts of zinc, sodium azide, and aluminum trichloride. 

This version of the Curtius rearrangement has been applied to the synthesis of amino acid analogs and structures containing amino acids. Several m-2-aminocyclopropane carboxylate esters were prepared by selective hydrolysis of cyclopropane-1,2-dicarboxylates, followed by reaction with DPPA.267... 

The pyrido[3, 4 4,5]furo[3,2-A]indole 24 can be prepared by Curtius rearrangement of 3-[5-(2-nitrophenyl)-2-furyl]-propenoic azide 25, followed by reduction of the nitrophenyl functionality of the product 26, chlorination of the tetracyclic product (PCI5), then reduction (Zn/AcOH) to give the parent compound 24 <1987CCC192> (Scheme 7). 

The bisamide odorine-roxburghilin and its dihydro derivative have been synthesized twice via Curtius rearrangement of a proline azide (127). The two syntheses followed similar lines and differed only in the preparation of the azide and in the solvent for rearrangement (104, 105). The stereospecificity of the Curtius rearrangement was an important argument for the determination of the absolute configuration of odorine (Scheme 23). 

The application of the Hofmann and Curtius rearrangement to the preparation of 2-thienvb)cetaldehyde (55) was studied, utilizing the degradation employed by Weerman. These reactions could be represented as follows ... 

Curtius rearrangement of the appropriate carboxylic azides has been used to prepare 3-, and 5-amino-1,2,4-oxadiazoles <66JCS(C) 1522>. 

Benzhydroxamic chloride reacts with sodium cyanamide (153) in dry acetone to give (154), a compound which has alternatively been prepared by Curtius rearrangement of the azide (155)... 

The pyrido[3,2-rflpyrimidines 370 were prepared from 2,3-pyridinedicarboxylic acid anhydride 366 by the action of boiling MeOH to give the stable isomer of half-ester 367. Subsequent treatment with ethyl chloroformate in presence of EtsN and NaNs formed the azide 368 that was transformed by Curtius rearrangement into the isocyanate 369. Reaction of 369 with a series of amino acids under mild conditions gave adducts 370 (Scheme 12) <2003TL2745>. 

Preparation of sy/n-diphenylureas by the Curtius rearrangement of m-and p-substituted benzazides in toluene [96]. 

Heteroaromatic vinyl isocyanates have been used as a source of bicyclic pyridones. In the preparation of the l-methylpyrazolo[4,3-c]pyridone 153 the isocyanate 152b, obtained by Curtius rearrangement of the corresponding acid azide 152a, was heated at 220°C in diphenyl ether to furnish the product in good yield.143,144 Several 2-alkyl derivatives were also prepared.144... 

Eloy and Deryckere have applied their synthesis of isocarbostyrils (69HCA1755) to the preparation of thieno[2,3-c]- and thieno[3.2-c]-pyridines (Scheme 65) (70BSB301). Thermal-cyclization of 3-thienylvinyl isocyanate prepared from the corresponding azide (269) by Curtius rearrangement yields thieno[2,3-c]pyridin-7-one (270), which is transformed to (259) following usual methods. 

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