1-Substituted tetrazole 3-oxide

Three 2-substituted tetrazole 1-oxides 550 representing the parent structure 548 (Scheme 163) have been reported (1913G71, 1983BAU181, 1984BAU142) (Scheme 165). These N-oxides are hygroscopic and crystallization with 0.5 mol of water has been observed. IR and H NMR data have been reported (1984BAU142). 

The 2-substituted tetrazole 1-oxides 550 were prepared from the corresponding hydroxytetrazoles 549 by methylation with trimethyloxonium tetrafluoroborate in CH2C12 at 20°C (1984BAU142) or by benzoylation of 1-hydroxytetrazole 549 (1913G71) (Scheme 165). Since N-alkylation and... 

The 2-substituted tetrazole 1-oxides 550 were readily deoxygenated by treatment with P + HI (1984BAU142). 

In the course of a series of studies on oxidations of /Tlactam-substituted tetrazoles carried out by a Hungarian research group <1999T8457>, cyclization to some fused tetrazolo[l,2-tf]pyrazines has been observed. The results are shown in Scheme 21. 

Thus, the substituted tetrazoles 113 upon oxidation with lead tetraacetate gave rise to the fused tetrazoles 114, in most cases in high yields. Tetrazole derivatives 115, bearing an anisidine side chain, also underwent oxidative cyclization and afforded 10-methoxycarbonylmethyltetrazolo[l,5- ]quinoxaline 116 in good yield. This compound was obtained as a mixture of tautomers (with participation of the methylene hydrogen atoms) and the depicted tautomeric form 116 proved to be dominant. 

No 1-substituted tetrazole 2-oxides derived from structure 544 have been found in the literature (Scheme 161). 

A series of 2,5-disubstituted tetrazoles 546, which remained unchanged when treated with 3-chloroperbenzoic acid, dimethyldioxirane, or H202 in AcOH under microwave heating, could be oxidized at the 3-position by excess of HOF in MeCN at room temperature producing 1-substituted tetrazole 3-oxides 547 in excellent yields. The reaction was insensitive to electronic or steric effects imposed by the substituents. A methylthio substituent was oxidized completely to methylsulfone before oxidation of the tetrazole ring occurred (2010JOC3141) (Scheme 163). 

Upon heating to 129°C 3-substituted tetrazole 1-oxides 557 rearranged into 4-substituted tetrazole 1-oxides 559, see Section 6.6. 

Three 4-substituted tetrazole 1-oxides 560 (Scheme 171) derived from the parent structure 559 (Scheme 170) have been described. H NMR, C NMR, 14N NMR, and 15N NMR data have been obtained (1989BAU1488). Line broadening of NMR signals provided information about the rate constant of the equilibrium between the A/-oxides 554 and 559 observed at elevated temperatures. 

Alkyl-substituted tetrazole 1-oxides 560 have been prepared by alkylation of the corresponding 1-hydroxytetrazole 555 with methylvinyl ketone to give a mixture of N-oxide 560 and the O-alkylated isomer 556 (1989BAU1488). Methylation of the A/-hyd roxytetrazole 555 with trimeth-yloxonium tetrafluoroborate afforded a mixture of N-oxide 560 (Alk=Me), an isomeric N-oxide of unknown structure, and the 1-methoxytetrazole 556 (Aik=Me) (1984BAU142) (Scheme 171). 

In another approach 3-substituted tetrazole 1-oxides 557 were isom-erized to the 4-substituted analogues 560 by heating to 120°C for 2h (1984BAU142) (Scheme 172). 

Heating 4-substituted tetrazole 1-oxides 560 gives rise to an equilibrium mixture of 560 with the corresponding 3-substituted isomer 557 (1989BAU1488). 

Substituted tetrazole 1-oxides 557 were N-dealkylated by treatment with K0H+AgN03 in ethanol solution with formation of 1-alkoxytetra-zoles 556 (1989BAU1488). 

---