Yu. I. Ryabukhin

Chemistry of 1,3-Thiazin-4-ones and Their Derivatives

Publisher Summary 1,3-thiazin-4-ones (TAs) have been the subject of intensive work owing to the uniqueness of their chemistry and the significant biological activity of many of these compounds. Traditionally, the methods of TA syntheses have been classified according to the number of atoms included in the fragments used for the construction of the heterocyclic ring. However, both the availability and structure of the starting materials are undoubtedly important in choosing a synthetic method. The chapter describes each class of TA by starting with the structures of the initial compounds and then illustrates analogous reactions in general schemes. The reactivity of TAs may be considered in two ways. The first consists in describing all the reactions of each separate class of compounds. The second approach is based on the classification into types of reactions of different compounds. The latter approach allows to focus on general and specific peculiarities of transformations and to compare the chemical behavior of various groups of TA derivatives. Progress in the chemistry of 1,3-thiazin-4-ones is mainly attributable to their applications in the pharmaceutical area. In the search for new drugs, the most intensive investigation has focused on the modification of substituents in the thiazinone ring and in the syntheses of thiazinones fused with heterocycles.

Synthesis of bis(o-hydroxyphenyl)-1,3,5-triazines, 1,2,4-triazoles, and oxadiazole by recyclization of the o-hydroxyphenyl-4-oxo-1,3-benzoxazinium cation

The acidic cyclization of disalicylamide gave 2-(o-hydroxyphenyl)- and 2-(o-acetoxyphenyl)-4-oxo-1,3-benzoxazinium perchlorates, by reaction of which with hydroxylamine, hydrazines, benzamidine, guanidines, and S-methylisothiourea bis(o-hydroxyphenyl)-1,2,4-oxadiazole, triazoles, and sym-triazines were synthesized. Mono- and bis (o-acetoxyphenyl) triazoles were obtained.

Photochromic and thermochromic spirans: VII. Spiro(4-oxo-3,4-dihydro-2H-1,3-benzoxazin-2,2?-[2H]benzophyrans)

New spiropyrans of the 4-oxo-3,4-dihydro-2H-1,3-benzoxazine series, individual representatives of which have photochromic properties, were obtained by condensation of 2-alkyl-4-oxo-1,3-benzoxazinium perchlorates with aromatic o-hydroxy aldehydes in acetic acid and subsequent treatment of the 2-(o-hydroxystyryl) derivatives with pyridine or triethylamine. The structures of the synthesized compounds were confirmed by the PMR, IR, and UV spectroscopic data.

Synthesis and study of the structure of o-hydroxyaryl-1,2,4-oxadiazoles

The reaction of 4-oxo-1,3-benz- and -naphthoxazinium perchlorates with hydroxylamine leads to 5-(o-hydroxyaryl)-1,2,4-oxadiazoles rather than to 3-(o-hydroxyaryl)-1,2,4-oxadiazoles, as was previously assumed. The structure of the compounds obtained was proved by alternative synthesis, as well as by mass spectrometry and comparison of the experimentally found and calculated dipole moments and Kerr constants of the possible structures of the o-hydroxyaryl-1,2,4-oxadiazoles.

Synthesis of derivatives of 1,2,4-oxadiazole, 1,2,4-triazole, and 1,3,5-triazine

Diuretics [1], analgesics, and antispasmolytics [2], as well as herbicides [3], fungicides [4], and nematocides [5], have been found among 1,2,4-oxadiazoles, 1,2,4-triazoles, and 1,3,5-triazines. For the purpose of synthesizing similar heterocycles conraining the pharmacophoric 3-chloropropyl group, the previously unknown synthon 2-(3-chloropropyl)-4-oxo-l,3benzoxazinium perchlorate (VIII) was synthesized, and its reactions with 1,2and 1,3-dinucleophiles [hydroxylamine (I), hydrazine hydrate (II), phenylhydrazine (III), guanidine (IV), and S-methylisothiourea (V)] were investigated. The compounds synthesized I X XIII have promise not only as biologically active substances, but also as starting substances for the synthesis ofoxadiazoles, triazoles, and triazines with other pharmacophoric fragments by means of the exchange of the chlorine in the 3-chloropropyl substituent for amino, hydroxy, and other functional groups. The acylation of salicylamide (VI) with y-chlorobutyryl chloride in the solution in chloroform in the presence of pyridine as a catalyst and an acid-binding agent led to the synthesis of N-(3-chlorobutyryl)salicylamide VII. It can be seen that the reaction proceeds analogously to [2] by the O-N rearrangement o f t he initially formed O-acyl derivative of salicylamide VI. The acid cyclization of the amide VII using 70% HCI04 in the solution of acetic anhydride and glacial acetic acid [6]

Molecular and crystal structure of 1-phenyl-3-methyl-5-(o-hydroxyphenyl)-1,2,4-triazole

A choice between the possible mechanisms of the recyclization of 4-oxo-1,3-benzoxazine salts due to reaction with phenylhydrazine was made based on the x-ray structure of 1-phenyl-3-methyl-5-(o-hydroxyphenyl)-1,2,4-triazole.

Acylation of salicylnitrile and salicylaldoxime as a method for the synthesis of 4H-1,3-benzoxazin-4-onium salts

Methods were developed for the synthesis of 4H-1,3-benzoxazin-4-onium salts by acylation of salicylnitrile and salicylaldoxime with acid anhydrides and chlorides are acids in the presence of perchloric acid or tin perchlorate.

Recyclization of 4-oxo-1,3-benzoxazinium perchlorates to 4-substituted 5-(o-hydroxyphenyl)-1,2,4-oxadiazolium salts

It was observed that N-substituted salts I are converted to the previously unknown oxadiazolium perchlorates II in 3650% yields by the action of hydroxylamine. Perchlorates II cannot be obtained by alkylation of the corresponding oxadiazoles of the III type, which were described in [1]. Thus the isomeric (with respect to salt IIa) perchlorate IV is formed when III is heated in dimethyl sulfate with subsequent dilution of the mixture with ether and treatment of the oily methylsulfonate with HC104 in AcOH. This reaction pathway is explained by the fact that the electron density on the N(2 ) atom of oxadiazole III is significantly higher than on N(4 ) [2] and by the fact that the N(4 ) atom is chelated by an intramolecular hydrogen bond.

Synthesis and transformations of 4(5H)-oxazolones and their salts (review)

The literature data on the synthesis and transformations of 4(5H)-oxazolones and their salts are correlated. An evaluation of the possibilities of the preparative utilization of the examined reactions is given.

Recyclization of 4-oxo-1,3-benzothiazinium salts. Synthesis of o-mercaptophenyl-1,2,4-triazoles and metal chelates based on them

A method based on the reaction of 4-oxo-1,3-benzothiazinium perchlorates with hydrazines is developed for synthesizing 5-(o-mercaptophenyl)-1,2,4-triazoles. Their complexes with Ni(II), Co(II), and Zn(II) are prepared. The o-mercaptophenyltriazoles are capable of undergoing oxidative dimerization to give disulfides.