1.2.4- Triazole 1-methyl-, ring synthesis

Ring closures of 3-mercapto-4-amino[l,2,4]triazole with benzoin or related compounds is also a well-established approach for the synthesis of the title compounds (with Table 5, entry 5, (tosyloxy)methyl 2-hetarylketones were used). These procedures are summarized in Table 5. 

The starting material for the synthesis of the 4-substituted derivatives 176 was the tautomeric 4(7)-nitrobenzo-triazole 173, which upon methylation with dimethyl sulfate in aq NaOH afforded the 4-nitro-2-methylbenzotriazole 174. The H NMR spectrum of the purified reaction mtKture after methylation showed the existence of all three triazole ring iV-methylated isomers in equal amounts. Compound 174 was isolated by virtue of its insolubility in cone HCl. Purity of products was confirmed by gas liquid chromatography (GLC). 

It has further been observed69 that methyl substituents in the benzo ring may undergo the Anil Synthesis. Thus, 2-(/>-tolyl)-5-methylbenzo-triazole (158) reacts with 2 moles of the anil derived from benzaldehyde and p-chloroaniline to yield 2-(stilben-4-yl)-5-styrylbenzotriazol (159).69... 

The synthesis of a new series of tetrahydro-oxazolo[4,5-d]-1,2,3-triazoles (102) has been reported. The triazolium imide 1,3-dipole (104) reacted with ( )-cinnamaldehyde in refluxing ethyl methyl ketone. It is significant that it was to the C=0 bond of the a,/ -unsaturated aldehyde that the cycloaddition took place, yet analogous addition to benzaldehyde or aliphatic ketones was not possible. The primary products of the cycloaddition reaction (105) underwent a sigmatropic rearrangement to furnish the new ring system (102) as shown in Scheme 23 <90JCS(P1)2527>. 

The cycloadducts of cyclooctatetraene and its substituted derivatives with 4-phenyl- and 4-methyl-37/-triazole-3,5(4//)-dione and diethyl diazenedicarboxylate are intermediates in the synthesis of polycyclic structures5 10 l2 23. Furthermore, pyrolysis of the diethyl diazenedicarboxylate cycloadduct 12 affords diethyl 1.2.4a,8a-tetrahydro-l,2-cinnolinedicarboxylate with undetermined stereochemistry of the ring fusion23. 

The behaviour of alkyl groups situated on the triazole ring is comparable with those of benzene thus their oxidation followed by decarboxylation has been much used in synthesis. Derived functions such as CH2X (X = OH, hal) also behave as expected cf. 55JA1538), but acetoxylation (Scheme 43) of 4-hydroxy-3-methyl-l,2,4-triazole (125) with acetic anhydride to give (126) is remarkable (70JPR610). 

A number of polymerizable ultraviolet stabilizers have been synthesized and their homo- and copolymerization studied. The initial work consisted of the synthesis of vinyl derivatives of methyl salicylate (three isomers), 2, -dihydroxy-benzophenone, and ethyl a-cyano-p-phenylcinnamate. More recently, vinyl derivatives (two isomers) and one isopro-penyl derivative of 2(2-hydroxyphenyl)2H-benzotriazole have been prepared. A number of benzotriazoles with more than one benzotriazole ring in the molecule, or compounds with both benzo(or aceto)phenone and 2(2-hydroxyphenyl)2H-benzo-triazole groups in one molecule, have also been synthesized. Acryloyl and methacryloyl derivatives of benzotriazole-substituted polyphenols have been prepared and homo- and copolymerized. 

In the synthesis of 173, the relative stereochemistry is set in the addition of a 4-(l-metallo-ethyl)-5-fluoropyrimidine derivative to l-(2,4-difluorophenyl)-2-(17/-l,2,4-triazol-l-yl)-l-ethanone 174 (Scheme 12.27). The diastereocontrol of this can be controlled by pyrimidine substitution pattern and reaction conditions of the metalation step. Good diastereoselectivity (12 1) is obtained using an zinc derivative of 175. After removal of the chlorine from the pyrimidine ring, of the desired stereoisomer of 173 is isolated via a diastereomeric resolution using salt (l/ )-10-camphorsulfonic acid (10-CSA). Synthetic routes to the pyrimidine partner have also been evaluated. Shown in Scheme 12.28, the initial six-step route from 5-fluorouracil 177 can be replaced by a four-step process, involving fluorination of methyl 3-oxopentanoate and cyclization with formami-dine acetate. ... 

---