Tetrazole acylation

Acidic ionizable center (negatively charged at physiological pH of about 7) (e.g., carboxylic acid, unsubstituted tetrazole, acyl sulfonamide)... 

Whether tetrazoles are acylated in the 1- or 2-position depends on the 5-substituent. 2-Acyltetrazoles are unstable (see Section 4.02.3.12.4) (77AHC(21)323) 1-alkylsul-fonyltriazoles are also unstable (see Section 4.02.1.2.3). 

Tefrazolo[2,3-e]isoxazole, 2-methyl-IR spectra, 6, 978 Tetrazol-5-one, 1-aryl-acylation, 5, 821 Tetrazol-5-one, 1,4-dimethyl-2-oxides synthesis, 3, 533... 

Tetrazole, trifluoroethanol, 24 h, 95% yield. These conditions will also cleave the A-trityl group. If deprotection is performed in the presence of an acylating agent, acylation proceeds directly. 

Aminosodium salt and acylated with 1 H-tetrazole-1 -acetyl chloride. The acetoxy group is then displaced by reaction with 5-methyl-1,3-4-thi-adiazole-2-thiol in buffer solution. The product acid is converted to the sodium salt by NaHCOa. 

Disubstituted tetrazoles are conveniently prepared from acyl hydrazines (98) and diazonium salts.166 The reaction proceeds through the intermediate tetrazenes (99) followed by cyclization to the tetrazole (100) (Scheme 13). The intermediate can be isolated under mildly basic conditions. Symmetrically 1,2-diacylated hydrazines yield 1-substituted tetrazoles through the elimination of one of the acyl groups.166 - 168 Diformyl-hydrazine is a very convenient starting material for 1-substituted tetrazoles.166, Unsymmetrically 1,2-diacylated hydrazine usually results in mixtures.169... 

Semiempirical calculations have been carried out for the transformation of N-acyl-tetrazoles into l,3,4-oxadiazoles.[144a]... 

Substituted tetrazoles reacting in the mass spectrometer with acyl ions afforded 2,5-disubstituted 1,3,4-oxadiazoles with nitrogen loss. Tandem mass spectrometry allowed for the collision-induced dissociation of the products. Chemical ionization was the better method to make the transformation. A scheme for the transformation of 5-substituted tetrazoles into 2,5-disubstituted 1,3,4-oxadiazoles was proposed (Scheme 1) <2001JMP1069>. The fragmentation patterns of monocyclic l,3,4-oxadiazolium-2-thiolates have been proposed by Ollis and Ramsden <1974J(P1)645>. 

The conversion of acyl isothiocyanates 47 with sodium azide leads to thiol-functionalized tetrazole derivatives such as 48 (Scheme 9) <1995PJC1022>. The reaction of 48 with chloro acetonitrile leads to an intermediate 49 that reacts in... 

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]. 

Cefpiramide (64) is a third generation cephalosporin with a l-methyl-[lH]-tetrazol-5-ylthio-methyl moiety at C-3 and an acylated p-hydroxyphenylglycine moiety at C-7. It includes in its activity spectrum reasonable potency in vitro against many strains of Pseudomonas. It can be synthesized in a variety of ways including condensation of cephalosporin antibiotic 63 with 6-methyl-4-(l-H)-pyridone-3-carboxylic acid in the form of its active N-hydroxysuccinimide ester (62) to produce cefpiramide (64) [20,21]. 

Ceforanide Ceforanide, (6R, 7R)-7[2-(a-amino-o-tolyl)acetamido]-3-[[[l-carboxymethyl-17/-tetrazol-5-yl]-thio]methyl]-8-oxo-5-thia-l-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid (32.1.2.27), is also structurally related to cefamandole, differing in that the acylating acid was o-aminomethylphenylacetic acid, and also in the presence of a carboxyl group in the methyl substituent of the tetrazol ring. It is also synthesized by methods analogous to the synthesis of cefamandole [124-128]. 

The amino group at tetrazole C-5 behaves as a normal nucleophile towards electrophilic acylating agents but acylation may also occur at the tetrazole N-1 or N-2 positions often giving ring degra-... 

The synthesis of valsartan (2) by Novartis/Ciba-Geigy chemists is highlighted in Scheme 9.5. Biphenylbenzyl bromide 18 is converted to biphenyl acetate 19 in the presence of sodium acetate in acetic acid. Hydrolysis of 19 followed by Swern oxidation delivered the biphenyl aldehyde 20, which underwent reductive amination with (L)-valine methyl ester (21) to give biphenyl amino acid 22. Acylation of 22 with penta-noyl chloride (23) afforded biphenyl nitrile 24, which is reacted with tributyltin azide to form the tetrazole followed by ester hydrolysis and acidihcation to provide valsartan (2). [See Biihlmayer et al. (1994, 1995).]... 

Aryloxy-tetrazole reagieren in siedendem Benzol mit Benzoyl-chloriden iiber die primaren 1-Acyl-tetrazole unter Stickstoff-Abspaltung zu 5-Aryl-3-aryloxy-l, 2,4-oxadiazoIen227 z.B. ... 

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