Degradation Curtius

Curtius degradation represents an interesting method for their one-step conversion into enan-tiomerically pure amines of the structure R RkTH—NH2. 

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These compounds are easily prepared from the appropriate 2-aminothiazole and acyl chloride (see Section III.2.D) or by general heterocydization methods. Acyl chlorides may be replaced by the corresponding anhydrides (471). Acids themselves may be used as acylating agents provided that the imidazole-triphenyl phosphine mixture is used as a catalyst (472). The Curtius degradation of 247 yields 2-acetamido-4-phenylthiazole (248) (Scheme 149) (473). 

Current Patents Curry and curry powder Curry powder Curtain spin process Curtius degradation Curved laminates Curvilinear regression Curvularia falcata Curvularia lunata var. aeri Curvularia trifolii Curzate... 

Special reactions of hydrazides and azides are illustrated by the conversion of the hydrazide (205) into the azide (206) by nitrous acid (60JOC1950) and thence into the urethane (207) by ethanol (64FES(19)105Q) the conversion of the same azide (206) into the N-alkylamide (208) by ethylamine the formation of the hydrazone (209) from acetaldehyde and the hydrazide (205) and the IV-acylation of the hydrazide (205) to give, for example, the formylhydrazide (210) (65FES(20)259). It is evident that there is an isocyanate intermediate between (206) and (207) such compounds have been isolated sometimes, e.g. (211). Several of the above reactions are involved in some Curtius degradations. 

Pyrimidine-5-carboxamide, 4-amino-purine synthesis from, 5, 582 Pyrimidine-5-carboxamide, 4-amino- N- pheny synthesis, 3, 122 Pyrimidinecarboxamides Curtius degradation, 3, 82 dehydration, 3, 82 Hofmann degradation, 3, 82 hydrolysis, 3, 81 reactions, 3, 81 synthesis, 3, 127 Pyrimidinecarboxamides, thio-synthesis, 3, 128... 

Pyrrole-2-carboxamide, N,N-dimethyl-conformation, 4, 194 Pyrrole-3-carboxamide, N,N-dimethyl-conformation, 4, 194 Pyrrolecarboxamides synthesis, 4, 242 Pyrrole-2-carboxamides synthesis, 4, 148, 360 Pyrrolecarboxylhydrazides Curtius degradation, 4, 362 Pyrrole-2-carboxylic acid, l-benzyl-3-hydroxy-ethyl ester... 

Putrescine dihydrochloride has been prepared by the Hofmann degradation of adipamide 3.. s by the Curtius degradation of adipyl hydrazide through the urethane by the Curtius degradation of adipyl azide obtained from adipyl chloride and sodium azide by the Schmidt degradation of adipic acid with hydrogen azide by the reduction of succinonitrile, succinaldoxime, or 7-phthalimidobutyronitrile with sodium and from N-ben-zoyl-7-iodobutylamine ... 

Prior to the 1947 report by Cook and Heilbron on their novel synthesis, 5-aminothiazoles were mostly unknown in the literature. Previous syntheses included the Curtius degradation of ethyl thiazole-5-carboxylates which did not have general applicability there was also difficultly in obtaining the necessary starting materials. During a study on penicillin, Cook and Heilbron found that the reaction between methyl dithiophenylacetate and ethyl aminocyanoacetate gave what was initially believed to be ethyl phenylthionacetamidocyanoacetate 4. However further studies proved the compound to be 5-amino-4-carbethoxy-2-benzyl-thiazole 5, which was basic. 

Early attempts to prepare 5-amino- and 5-acylaminobenzofuroxans by hypochlorite oxidation of the corresponding o-nitroanilines met with failure. Pyrolysis of the appropriate azide, however, gives 5-dimetliylamino- and 5-acetamidobenzofuroxan, whereas urethans of type (33) are produced by Curtius degradation of the 5-carboxylic acid. Controlled hydrolysis of the acetamido compound and the... 

Several reactions of quinoxalinecarboxamides and related derivatives have been discussed already the Hofmann or Curtius degradation to quinoxalinamines (Section 6.3.1), hydrolysis to quinoxalinecarboxylic acids (Section 7.1.1), and... 

Aminopyrazole has been prepared by a Curtius degradation of pyrazole-3(5)-carboxylic acid hydrazide,2 3 by saponification and decarboxylation of ethyl 3-aminopyrazole-4-carboxy-late 4 obtained from ethyl ethoxymethylenecyanoacetate and hydrazine, and by the present procedure.6,6... 

Currie, J. N., 11 8 Curry powder, 23 166-167 Curtain coating, 7 20-21 method summarized, 7 5t shear rates, 7 32t Curtain spin process, 17 473-474 Curtius degradation, 2 573 Curved surgical needles, 24 206-207 Curve-fitting procedures, 14 237 Cusping, in fine art X-radiography,... 

Conversion to carbamates. Cyclic carbamates derived from sugars and related compounds have repeatedly been encountered, the first being an inosamine derivative, obtained by Curtius degradation of dihydroshikimic acid.82,83... 

Although excellent yields of the unsaturated amides and urethans could be obtained, hydrolysis of the urethans gave poor yields of the aldehyde. The application of the Curtius degradation resulted in excellent yields of the various intermediates and a fair yield of the aldehyde. It appears that the presence of the heterocyclic moiety renders these aldehydes less stable than the corresponding aldehydes in the benzene series. Possibly the electron rich thiophene ring bestows a higher reactivity on the hydrogen atoms of the methylene carbon. 

Cope and LeBel (60JA4656) prepared the cis laetone 81 from eyclo-pentane-c -l,2-dicarboxylic anhydride and converted it to the hydrazide 82. Curtius degradation of 82 gave the cyclic urethane 83. 

Anhydride 150 and trimethylsilyl azide in dioxane yielded an acyl azide, which by thermolysis, and Curtius degradation spontaneously furnished the isocyanate 151 (72CB3958 74CB3533). Anhydride 152 was formed by silyl ester cleavage on hydrolysis [73MI2 90JCS(P1)375]. 

Curtius degradation of the acyl azide and subsequent transesterification with tert-butanol and hydrolysis resulted in the A/-BOC amino acid 156. Compound 156 was readily cyclized with thionyl chloride, resulting in anhydride 157 diendo, R = H, Me diexo, R = H) in one step. In the cyclization step, acid chlorides were formed first and thereafter an intramolecular cyclization took place with loss of hydrogen chloride (93BSB227,93T1985). 

Several derivatives of lH-cycloprop[/]indene have been synthesized. The di-fluoro compounds 212 (X = 0,S) were obtained by the cycloaddition route from 188 in analogy to the synthesis of 191 and 192. The cycloaddition of diene 213 to 1,2-bromochlorocyclopropene (27) provided 214, which was aromatized to 217. Twofold Curtius degradation of 214 afforded the ketone 215. While attempted aromatization of 215 with base afforded no cycloproparene, the corresponding alcohol 216 reacted with base to 218 in acceptable yield. The alcohol 218 is also accessible from 219. ... 

Two examples illustrate the formation of amino groups at 1- or 2-positions of dibenzopyridoazepines the route from carboxylic acid 354c by Curtius degradation through mixed anhydride to yield amine 391... 

Amino or A-BOC-amino pyrazines have been produced by Curtius degradation of pyrazinecarbonyl azides in 7-butanol (Equation 30) <1999JA8783>. 

Indanone was first prepared by distillation of the calcium salt of o-phenylenediacetic acid2 3 and, more recently, by the action of acetic anhydride on its potassium salt.4 It has been obtained by the dilute sulfuric acid-catalyzed hydrolysis and decarboxylation of 2-iminoindan-l-carboxylate6 and ethyl 2-indanone-l-carboxylate.6 2-Indanone is commonly obtained by acid-catalyzed dehydration of an indene glycol,7 8 as illustrated in this preparation. Indene glycol has been obtained from indene via the bromohydrin.9-12 The most recent preparation of 2-indanont is by Curtius degradation of 2-indenecarboxylic acid.13... 

The C-2 or C-3 amino derivatives of pyrroles can be obtained by reduction of nitro or nitroso pyrroles or by Curtius degradation of pyrrolecarboxylhydrazides. A few ring closures give 2-aminopyrroles directly (see Section 3.06.2.3, for example), but these are rather specialized (B-77MI30608). 

Amines have been prepared on insoluble supports by Hofmann degradation of amides [222] followed by hydrolysis of the intermediate isocyanates (Figure 10.5). One reagent suitable for this purpose is [bis(trifluoroacetoxy)iodo]benzene, which can be used both on cross-linked polystyrene [223] and on more hydrophilic supports such as polyacrylamides (Figure 10.6). Support-bound carboxylic acids can also be degraded via the acyl azides (Curtius degradation [224,225]) to yield isocyanates. 

Figure 10.5. Hofmann and Curtius degradation of support-bound amides and acids.

Support-bound aliphatic alcohols react smoothly with isocyanates in the presence of catalytic amounts of a base to yield carbamates (Table 14.7). In an interesting variant of this reaction, isocyanates were generated in situ by Curtius degradation of acyl azides (Entry 2, Table 14.7). 

Support-bound isocyanates can be conveniently prepared from carboxylic acids by Curtius degradation. Because the reaction of the intermediate acyl azides with alcohols to yield esters is slow, Curtius degradation can be conducted in the presence of alcohols to yield carbamates directly (Entries 4 and 5, Table 14.8). 

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