Hydrazides rearrangement with acid

The tendency of compounds RCN3=X to cyclize depends on the nature of X. When it is oxygen only open chain compounds are detected , and similarly for hydrazidic acids, RCNg=NNHAr, attempts to synthesize the cyclic form were failures . The latter type of compounds rearranged on treatment with acid to form semi-carbazides with retention of configuration. Guanyl azides can be isolated in open chain forms that cyclize on heating (reaction 94). 

Carboxylic acid hydrazides from carboxylic acid esters GOOR -v CONHNHg with cis-frans-rearrangement s. 17, 413... 

The thermal decomposition of acyl azides into isocyanate intermediates is known as Curtius rearrangement reaction (Scheme 5.2) [27, 28]. Conventionally used general methods to synthesize aroyl azides are limited to diazotization of hydrazides and reactions of NaNs with acid chlorides, mixed anhydrides, and Al-acyl benzotriazoles [35-38]. However, these procedures involve highly reactive chemicals which put significant limitations on functionalities of the substrate. The development of methodologically new, highly functional-group tolerant, catalytic routes to aroyl azides is particularly desirable. 

Benzofuran isocyanate was prepared by Curtins rearrangement from 2-benzo-furoyl azide with acid hydrazide under microwave irradiation (Wang et al., 2006). A series of asymmetric semicarbazides was synthesized by reactions of 2-benzofuran isocyanate. This method gives high yield under mild conditions compared to the conventional method. 

Chai et al. (2013) reported the synthesis of a series of styrl substituted semicarbazides by reaction of trans-styiyl isocyanate, which was prepared by Curtius rearrangement of ciimamoyl azide, with acid hydrazides under microwave irradiation using a one pot procedure. Comparing to the conventional method, this method was advantageous, because of mild conditions, easy handling, and high yield. 

Scheme 166 shows application of this methodology for preparation of hydrazide 1007. Thus, the reaction of acid 1004 with 1-hydroxybenzotriazole and EDC [l-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride] gives ester 1005 that can be separated and characterized, but it rearranges slowly to isomeric form 1006 in solutions. However, both derivatives, 1005 and 1006, are found to be equally reactive toward hydrazine and afford hydrazide 1007 in 98% isolated yield <2002JOC9471>. 

Spirocyclic oxindole 60 was synthesized by [3,3]-sigmatropic rearrangement of the Af-phenyl-O-acylhydroxamic acid 58 (equation 19). The potassium enolate formed by treatment of 58 with potassium hexamethyldisilazide at low temperature rearranged to 59, which easily cyclized to the spirocyclic oxindole 60. Spirooxindoles were previously synthesized by Wolff and Taddei. The spirooxindole 60 was formed in 51% yield from cyclohexanecarboxylic acid after heating the preformed lithium salts of phenyl hydrazide 61 to 205-210 °C. 

Curtius rearrangement of a-oximino acid azides is reported as a new method of synthesis for 3-substituted 5-hydroxyoxadiazoles. In this method, the oxime of an a-ketoester is converted to the acid hydrazide, which in turn is converted to the azide by reaction with nitrous acid 115a). 

Goodman and Chorev 75 found that the required a-aminoacyl azides 14 are best prepared by reaction of the mixed anhydride of the amino acid with sodium azide. This method led to slightly better yields than the nitrosylation of TV-formylaminoacyl hydrazide. Curtius rearrangement of the a-aminoacyl azide 14 yielded the isocyanate 16, which was subsequently trapped as 17 or 18 as shown in Scheme 2. Comparable yields were obtained by nitrosylation with tert-butyl nitrite. 76 Other methods of acyl azide formation have rarely been employed for PMRI-peptide synthesis. Only Fincham et al. 11 reported the use of trimethylsilyl azide to synthesize an acyl azide en route to a PMRI-peptide. 

If primary or secondary amines are used, AT-substituted amides are formed. This reaction is called aminolysis. Hydrazines yield the corresponding hydrazides, which can then be treated with nitrous acid to form the azides used in the Curtius rearrangement. Hydroxyl amines give hydroxamic acids. 

An ester group at C-3 or C-5 is not different in function from any ester in aliphatic or aromatic compounds. The ester can be converted into an amide or a hydrazide, or it may be hydrolyzed. The hydrazide can be converted into an acid azide and rearranged to an isocyanate which in turn will form a carbamate or can be hydrolyzed to an amine. However, the amine group can be replaced with chlorine by diazotization in hydrochloric acid, not an ordinary pattern of behavior (76AHC(20)65) although similar reactions do occur in the 1,2,4-triazole ring system. 

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