Azides acyl, thermolysis

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). 

Thermolysis of acyl azides and subsequent cyclization to give aziridines has been reported by Egli and Dreiding [39]. Heating of acylazide 34 (Scheme 3.11) in an autoclave afforded aziridine 35 in 74% yield [39]. 

Section A of Scheme 10.15 contains a number of examples of Curtius rearrangements. Entry 1 is an example carried out in a nonnucleophilic solvent, permitting isolation of the isocyanate. Entries 2 and 3 involve isolation of the amine after hydrolysis of the isocyanate. In Entry 2, the dihydrazide intermediate is isolated as a solid and diazotized in aqueous solution, from which the amine is isolated as the dihydrochloride. Entry 3 is an example of the mixed anhydride procedure (see p. 948). The first stage of the reaction is carried out in acetone and the thermolysis of the acyl azide is done in refluxing toluene. The crude isocyanate is then hydrolyzed in acidic water. Entry 4 is a reaction that demonstrates the retention of configuration during rearrangement. 

Figure 4.8 Thermolysis of an acyl azide to produce an isocyanate.

The tetrazole procedure that has been proved to be of value in the thiazolo[3,2-6][l,2,4]triazole series (see Section VIII) has also been applied in this field. V-Acylated 2-aminothiadiazoles 193 on treatment with phosphorus pentachloride (120°C) and subsequently with sodium azide (aqueous acetone) yield tetrazoles 194. Thermolysis in tetraline (160-180°C) gives the heterocycles 195 in moderate yields [85IJC(B)908 WFA953]. 

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]. 

The nitrene 28 is not produced from the azide precursor, but from heterocycles via photolysis and thermolysis as shown in Sch. 11 [20]. Iminoacyl nitrenes react intramolecularly giving benzimidazoles with good yields (Sch. 11), and, dependending on the precursor used and the reaction conditions, varying amounts of carbodiimides are obtained. The reactivity of the acyl nitrenes is influenced by the substituent connected to the acyl group (see Sch. 10), however all acyl nitrenes are quite reactive and therefore rather unselective. Apart from cycloaddition reactions with Tt-bonds, insertion reactions into a-bonds, additions to lone pair electrons of... 

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... 

Common methods for generating nitrene intermediates are the photolysis and thermolysis of azides. Generation of nitrenes from acyl azides can only be effected photochemically thermolysis of an acyl azide gives the corresponding isocyanate. 

Although thermolysis of triazoline can also, in certain cases , lead to aziridines, mixtures with azomethines usually result, and the photochemical process is preferable. The triazolines formed from acyl ° or sulphonyl azides are unstable and the corresponding aziridines can be obtained directly. The reaction of norbomene and benzoyl azide at 40° yielded the aziridine (128) directly... 

The decomposition of diazotates may also be induced by Lewis acids. Solution of (152) in hexamethylphosphoric triamide are slowly decomposed by excess lithium azide or lithium chloride with the formation of inverted 2-octyl azide and chloride, respectively, along with retained 2-octanol1491. Diazotates are readily decomposed by acylation. Although the intermediate diazoesters (125) should be identical with those generated by thermolysis of nitrosoamides, differences in stereochemistry and product distribution were noticed which may be due to the heterogeneity of the diazotate system149-15 D... 

Acylnitrenes are formed by photolysis of acyl azides and react intramolec-ularly to form lactams.149 154 Evidence was adduced that it is a singlet nitrene which cyclizes to the lactam 108 on photolysis of the sulfilimine 107.155 Thermolysis gave only mesityl isocyanate (109).155 Isocyanates often,156 but not always157 accompany photolyses of acyl azides but generally this is thought to be a nonnitrene process (see below, however). 

PHOTOLYSIS AND THERMOLYSIS OF ACYL AZIDES PROPERTIES OF ACYLNITRENES... 

Construction of the l-thia-2,4-diazine 1,1-dioxide system by employing the Curtius rearrangement is also a useful approach. Thermolysis of acyl azides 194 (R = Pr", Bn, Ar) in benzene, chloroform, or xylene solution leads to the intermediate isocyanate 195, which cyclizes to give the isolated product 196 (Scheme 15) <2000EJM751, 1999BMC2811, 1997H(45)1767>. N-Alkylation of compounds related to 196 is addressed in Section 9.05.6.2.2. 

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