Azodicarboxylic acid rearrangement

The cycloadducts 257 of esters of azodicarboxylic acid to 2,7-dimethyloxepin undergo a spontaneous Claisen rearrangement to form the dihydrocyclopropapyridazines 258 (equation 139)132. Homofulvenes 259 (R1, R2 = HorMe) react with dimethyl azodicarboxylate to form rearranged adducts 260 (equation 140)133. 

Treatment of 6-arylidenehydrazino-3-alkyl-5-nitrouracils 510 with etha-nolic KOH caused a benzylic acid type of rearrangement to give 511, which were alkylated to give 512, whose cyclization with diethyl azodicar-boxylate gave (80H1295) 513 by intramolecular cycloaddition through valence isomerization and then aromatization with diethyl azodicarboxylate (Scheme 107). 

When treated with benzoic acid in the presence of triphenylphosphine and diethyl azodicarboxylate, benzophenone oxime gave a high yield of f -benzoylbenzanilide (14), formed via rearrangement of the intermediate 0>benzoyloxime (15). Reaction of p>medioxyaGetophenone oxime with l,rsubstituted derivative (l ), whereas in the presence of allyl bromide... 

A combination of triphenylphosphine and diethyl azodicarboxylate (the Mitsunobu reagent) is useful for the rapid conversion of aromatic hydroxamic acids (211) to 0-(yV-arylcarbamyl)hydroxamates (212), products of the Lossen rearrangement. In some cases, a spontaneous second Lossen rearrangement occurs to give diarylureas (213), as shown in Scheme 33. The yields of (212) and (213) are 70-85%. The intermediacy of the phosphonium salts (214) has been suggested. 

Nucleophilic Attack at Other Atoms. A Lossen rearrangement occurs when aromatic hydroxamic acids are allowed to react with the triphenylphosphine-diethyl azodicarboxylate complex in the presence of ethanol, to give the hydroxamates (49). 

A device which has been frequently used to produce a starting material with just one acyl group in place is to carry out a Beckmann rearrangement on an ortho-hydroxyaryl ketone, the Beckmann product cyclising in situ when the conditions are acidic a modern version of this is illustrated below." " An excellent route to mono-acylated precursors utilises mixed anhydrides.A very mild method for the dehydrative ring closure of or /io-hydroxyarylamino amides, employed in solid-supported benzoxazole syntheses, utilises typical Mitsunobu conditions - triphenyl-phosphine and diethyl azodicarboxylate." ... 

Esterification ofttUylic alcohols. Esterification of allylic alcohols with benzoic acid using triphenylphosphine and diethyl azodicarboxylate proceeds with inversion and without allylic rearrangement. ... 

Cycloadditions. Addition of diethyl azodicarboxylate or related derivatives to polyenes proceeds easily. Further examples of this important route are shown in Scheme 12. The ease with which these adducts may undergo Claisen rearrangement has been further studied. " Rearrangement is facilitated by ring strain and also by electron release from N-substituents (48) is stable even at elevated temperatures. The rearrangement is acid-catalysed. 

The rearrangement of a penicillin sulfoxide ester to a A -cephem, originally accomplished using toluenesulfonic acid, has also been achieved with a variety of reagents [e.g., dipyridinium phosphate (Barton et al., 1972 Baldwin et al., 1973), diethyl azodicarboxylate (Tereo et al., 1972), a,a-azobis-N-methylformamide (Tereo et al., 1972), and diethylphos-phorocyanidate (Ninomiya et al., 1976)]. This latter reagent was disclosed as also yielding small amounts of the A - and exomethylenecephem isomers. 

Dealkylation of Amines. Treatment of a secondary or tertiary amine with diethyl azodicarboxylate in nonpolar solvents followed by acidic hydrolysis leads to the formation of mon-odealkylated amines. The mechanism of this reaction is believed to involve the formation of a triaza adduct (by Michael addition) followed by a two-step ylide rearrangement yielding an alkyl-substituted hydrazocarboxylate. Research on unsymmetrically substituted amines suggests that benzyl groups are more easily removed than alkyl groups methyl groups are the hardest to remove except in cyclic amines like iV-methylpiperidine (eq 3). The Al-dealkylation of imines has also been reported. ... 

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