Azides Curtius degradation

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. 

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. 

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 ... 

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... 

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). 

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

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). 

Curtius degradation of acyl azides a. acyl azide from hydrazide... 

Curtius degradation of acyl azides (obtained from acid chlorides)... 

Curtius degradation.3 The reaction of the carboxylic acid 1 with this azide in t-butyl alcohol gives the Boc-protected amine 2 directly. 

CURTIUS DEGRADATION Diphenylphosphinyl azide. CYANOSELENANYLATION Phenyl selenocyanate. 

The mono-esters thus prepared have been used by Bolm et al. for selective synthesis of two-stranded peptidic structures with parallel arrangement of the peptide strands [12]. They also enable easy access to unnatural /i-amino acids in enan-tiomerically pure form. The latter reaction sequence involves conversion of the carboxyl group to an acyl azide and subsequent Curtius degradation [11, 13, 14]. 

The Curtius degradation of acyl azides (Figure 14.43) expels molecular nitrogen and at the same time leads to the [1,2]-rearrangement of the substituent that is attached to the carboxyl carbon. It is the simultaneous occurrence of these two events that prevents the formation of an energetically unacceptably disfavored acylnitrene intermediate. The rearranged product is an isocyanate. 

The isocyanate can he isolated if the Curtius degradation is carried out in an inert solvent. The isocyanate also can be reacted with a heteroatom-nucleophile either subsequently or in situ. The heteroatom nucleophile adds to the C=N double bond of the isocyanate via the mechanism of Figure 8.12. In this way, the addition of water initially results in a carbamic acid. However, all carbamic acids are unstable and immediately decarboxylate to give amines (see Figure 8.5). Because of this consecutive reaction, the Curtius rearrangement represents a valuable amine synthesis. The amines formed contain one C atom less than the acyl azide substrates. It is due to this feature that one almost often refers to this reaction as Curtius degradation, not as Curtius rearrangement. 

Fig. 14.44. A one-pot diastereoselective degradation of a carboxylic acid to a Boc-protected amine via a Curtius rearrangement Boc refers to tert-butoxylcarbonyl. The mixed anhydride B is formed by a condensation of the phosphorus ) reagent with the carboxyl group. The anhydride B acylates the concomitantly generated azide ion forming the acyl azide A. A Curtius degradation converts A to C, and the latter reacts subse-guently with tert-butanol to the Boc-protected amine.

Figure 14.44 also shows how the Curtius degradation of an acyl azide can be combined with the addition of ferf-butanol to the initially obtained isocyanate. This addition gives a carbamate. In the present case a fert-butoxycarbonyl-protected amine ( Boc-protected amine ) is formed. 

Fig. 14.45. Transformation of an a-phosphonylcarboxylic acid ester (B) via the related carboxylic acid azide F and its Curtius degradation in ethanol to furnish an ethoxycarbonyl-protected a-aminophosphonic acid ester E. The N- and 0-bound protective groups of the latter compounds are cleaved off under acidic conditions. In this manner a-aminophosphonic acids are synthesized. They are interesting analogs of the biologically important a-amino carboxylic acids.

The Curtius degradation of acyl azides (Figure 11.39) consists of the thermolysis of the inner N=N double bond. This thermolysis expels molecular nitrogen and at the same... 

The isomeric 6-methyl-8-amino-ergolenes (LXXVIa) and ergolines (LXXVIIa) were produced by a modified Curtius degradation of d-lysergic acid azide, of d-isolysergic acid azide, or of the isomeric d-di-hydrolysergic acid azides (149). 

Numerous aminocyclopropanes have been prepared by the Curtius degradation (Scheme 1). The acyl azides (15) were obtained in many cases from the acid chloride (16) and sodium azide either in an organic solvent ( Dry Sodium Azide Procedure ) or in water ( Wet Sodium Azide Procedure ). A modified preparation was reported by... 

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