Nagwa Rashed

Condensed 1,2,4-triazines. I: Fused to heterocycles with three-, four-, and five-membered rings

Publisher Summary Compounds containing the 1,2,4-triazine moieties are largely used as pharmaceuticals, dyes, pesticides, and herbicides. Great interest is directed to the synthesis of the title heterocycles having potentially useful biological properties. A large number of 1,2,4-triazines that are condensed with one or more heterocycles are well known and a wide variety of synthetic methods for their preparations are available. This chapter illustrates the triazines that are fused to heterocycles with three, four, and five-membered rings. It covers the survey of the literature of these condensed compounds from 1974 to 1992. The parent compound of this series has two Kekule structures. It can be fused with other heterocycles at its six different sites. The 1,2,4-triazine ring can also constitute a central unit in a condensed ring system, where two or more faces are included in fusions. It is noted that the heterocycles having fused benzene rings are categorized according to the heterocycle that is directly fused to the triazine ring.

Dimroth Rearrangement: Translocation of Heteroatoms in Heterocyclic Rings and Its Role in Ring Transformations of Heterocycles

Publisher Summary This chapter discusses the translocation of heteroatoms in heterocyclic rings and its role in ring transformation of heterocycles in dimorth rearrangement. The Dimroth rearrangement is an isomerization process whereby exoand endocyclic heteroatoms are translocated on a heterocyclic ring. It is also considered to be amidine rearrangement. This rearrangement may be classified into two main types. The translocation of heteroatoms in the first type can be between two rings of a fused system by three possible pathways: (1) an exocyclic heteroatom of a ring becomes endocyclic, (2) a heteroatom in a five-membered ring changes its location on the other ring, or (3) one of the heteroatoms of a five-membered ring becomes a substituent on the other ring and the other two heteroatoms of the same ring become a part of another five-membered ring on cyclization. The second major type involves the translocation of exo- and endocyclic heteroatoms on a single heterocyclic ring, an exoannular rearrangement, the mechanism of which has been studied since the early work on the subject. The rearrangement led to a translocation of the starred heteroatom. The Dimroth rearrangement can be catalyzed by alkali, acid, heat, or light.

1,2,4-Triazolo- and Tetrazolo[x,y-z]pyrimidines

Publisher Summary This chapter reviews the chemistry, biological significance, and uses of 1,2,4-triazolo- and tetrazolo-[x,y-zl pyrimidines. The arrangement of each ring follows the order of the site of fusion on the pyrimidine ring, denoted by the letter t, and the site of fusion on the triazole ring, denoted by the letters x and y . The classification of the subdivisions is dependent upon the extent of published work. There are four possible isomeric structures: (1) 1,2,4-triazolo[4,3-a] pyrimidines, (2) 1,2,4-triazolo[4,3-c]pyrimidines, (3) 1,2,4-triazolo[l,5-a] pyrimidine, and (4) 1,2,4-triazolo[1,5-c] pyrimidines. A characteristic feature triazolopyrimidines is the ease of a Dimroth rearrangement. 1,2-Diaminopyrimidines are general precursors, and they can be generated from 1-amino or 2-aminopyrimidines. The synthesis of 1,2,4-triazolo[4,3-a] pyrimidines ring system may be achieved by building the triazole onto a preformed pyrimidine ring. The synthesis from pyrimidines, triazoles, reactivity, physicochemical data, uses, and biological properties of all these rings are discussed in the chapter.

Condensed 1,2,4-Triazines: II. Fused to Heterocycles with Six- and Seven-Membered Rings and Fused to Two Heterocyclic Rings

Publisher Summary This chapter deals with condensed ring systems of 1,2,4-triazines with six and seven-membered heterocycles, and condensed ring systems with triazine in the center. The chapter considers the order of increasing number of heteroatoms in the fused ring and each is followed in turn by a heterocycle fused to a benzene ring. Each fused ring system is arrangedaccording to the order of fusion on the triazine ring. Specifically, the chapter describes pyrido[1 ,2,4]triazines, pyrano[ 1 ,2,4]triazines, diazino[1,2,4]triazines, [ 1 ,2,4]triazino-oxazines, [ 1 ,2,4]triazino-thiazines, triazino[ 1 ,2,4]triazines, triazino-oxadiazine, triazino-thiadiazine, triazino-dioxazines, and heterocyclo-triazino heterocycles. With regard to pyrido[l,2,4]triazines, it is observed that there are eight theoretically possible pyridotriazines. Four of them possess bridgehead nitrogen with faces b , c , d , and f common to the triazine ring. The other four isomers have face e in common. Their UV spectral properties are generally dependent on the position of the pyrido N -atom.

C-(polyacetoxy)alkyloxadiazolines and related compounds

Abstract The (phenylacetyl)hydrazones of d -galactose, d -glucose, d -mannose, d -arabinose, l -arabinose, d -xylose, and l -sorbose were prepared. The d -galactose and d -arabinose derivatives were converted into their per- O -acetylated derivatives ( 8 and 9 , respectively). The acyclic structure of 8 was proved from its direct preparation by the condensation of(phenylacetyl)hydrazine with penta- O -acetyl-aldehydo- d -galactose. Cyclization of 2,3,4,5,6-penta- O -acetyl- aldehydo - d -galactose (phenylacetyl)hydrazone with boiling acetic anhydride yielded a mixture of two products that could be separated by fractional recrystallization, to give 3-acetyl-5-benzyl-2-(polyacetoxy)alkyl-1,3,4-oxadiazolines; a mechanism for the reaction was proposed. The n.m.r. and mass spectra of some of these derivatives were discussed.

Reaction of dehydro-d-erythorbic acid and its aryl analogs with ortho-diamines

Abstract Condensation of 3-( d - erythro -2,3,4-trihydroxy-l-oxobutyl)-2-quinoxalinone and its 6-chloro derivative (obtained by the reaction of d - erythro -2,3-hexodiulosono-1,4-lactone with ortho -diamines) with aryl- or aroyl-hydrazines gave 3-[l-(phenylhydrazono)- d - erythro -2,3,4-trihydroxybutyl]-2-quinoxalinone (5) and relatives. Whereas boiling acetic anhydride causes the loss of two molecules of water per molecule of such hydrazones, affording, the 3-[5-(acetoxymethyl)-l-arylpyrazol-3-yl]-2-quinoxalinones, identical with those obtained from the l - threo isomer, alkali causes the loss of only one molecule, affording, the corresponding flavazoles. Periodate oxidation of 5 gave 3-[l-(phenylhydrazono)glyoxal-l-yl]-2-quinoxalinone, which afforded the corresponding mixed bis(hydrazones). A similar sequence of reactions was conducted with the aryl analogs, 4-phenyl-2,3-dioxobutano-1,4-lactone and its p -chlorophenyl derivative, whereby the 3-[2-aryl-l-(arylhydrazono)-2-hydroxyethyl]2-quinoxalinones, were prepared; these were transformed into 3-(α-hydroxybenzyl)-flavazoles that gave monoacetyl derivatives.

Novel Regioselective Hydroxyl-Alkylation of 4,5-Diphenylimidazole-2-Thione and A Competitive Intramolecular Ring Closure of the S-Hydroxyalkyl-Imidazoles to Imidazo[2,1-b]Thiazines and Thiazoles. Role of Catalyst, Microwave Irradiation, and Solid Support

Under both conventional method (CM) and microwave (MW) irradiation (MWI) conditions, alkylation of 4,5-diphenylimidazole-2-thione (1) with halogeno-alkanols 2 or 5, chloroglycerol 11 and 2,3-O-isopropylidene-1-O-(p-tolylsulfonyl)-glycerol (8) in presence of sodium ethoxide or sodium acetate in alcohol afforded regioselectively the corresponding S-alkylated analogues 3, 6, 9, and 12; they also were obtained using MW in absence and presence of bentonite as solid support with no change in regioselectivity. In the presence of potassium carbonate in DMF, the bisalkylated analogues 4, 7, 10, and 13 were obtained except in case of compound 13 where it was accompanied with the imidazothiazine 14. A convenient approach for imidazo-[2,1-b]thiazines and thiazoles 14–16 could be achieved by intramolecular dehydrative ring closure of the S-hydroxyalkylated imidazoles 3, 6, and 12 using potassium carbonate in DMF under both conventional and microwave methods. Isopropylidenation of 12 and 13 and deprotection of 9 and 10 also were investigated.

2,3,4-Furantriones

Publisher Summary This chapter focuses on the synthesis of heterocycles from 2, 3, 4-furantriones (2, 3-dioxobutyrolactones). It describes the synthesis of the furantriones and also considers their nitrogen derivatives, which retain the furanone ring and are mostly the starting precursors for the heterocycles in the third and fourth parts. The heterocycles that retain the furanone ring and those that are produced by its rearrangement are also dealt with respectively. The synthesis of compounds possessing the furantrione ring is based essentially on the ready oxidation of the hydroxy tetronic acids. The chapter discusses the nitrogen derivatives of furantriones. The heterocycle may be fused to the furanone ring at various positions. Thus, the fusion may be on C-5 and C-4, C-4 and C-3, or C-3 and C-2. Otherwise the heterocycle may be linked to the C-5 of the furanone ring. Heterocycles from rearrangement of the furanone ring are also discussed.

Synthesis of 5‐Aryl‐3‐Glycosylthio‐4‐Phenyl‐4H‐1,2,4‐Triazoles and Their Acyclic Analogs Under Conventional and Microwave Conditions

Under microwave irradiation (MWI), 4‐phenyl‐5‐substituted‐4H‐1,2,4‐triazole‐3‐thiol derivatives 7 and 8 were synthesized in a good yield by intramolecular cyclization of the aroyl phenyl thiosemicarbazides 5 and 6. The respective triazolylglycosides (Str‐glycosides) 12–17 were obtained by reaction of triazoles 7 and 8 with glycosyl halides 9–11 in dry acetone in the presence of potassium carbonate as base under both conventional and MWI conditions. Alkylation of 7 and 8 with haloalchols 18–20 in boiling ethanolic solution containing sodium ethoxide as a base gave the corresponding alkylated analogs 21–26. MWI conditions led to higher yield in shorter reaction time than the conventional method. Treatment of 26 with tosyl chloride gave the unexpected product 29 and not 27 or 28. Oxidation of 26 with sodium metaperiodate afforded triazole 8 and not the aldehyde 30. Attempted glycosylation and alkylation of the phenolic OH group in triazole 8 were unsuccessful; this was proved by theoretical calculations using the AM1 semi‐empirical method.

Acyclo C-Nucleoside Analogs. Regioselective Annellation of a Triazole Ring to 5-Methyl-1,2,4-Triazino[5,6-b]Indole and Formation of Certain 3-Poly Hydroxyalkyl Derivatives

ABSTRACT Cyclodehydrogenation of the ethylidene derivative of (5-methyl-1,2,4-triazino[5,6-b]indol-3-yl)hydrazine (1) gave the angular isomer, 1,10-dimethyl-1,2,4-triazolo[3′,4′:3,4][1,2,4]triazino[5,6-b]indole (4). The linear isomer, 3,10-dimethyl-1,2,4-triazolo[4′,3′:2,3][1,2,4]triazino[5,6-b]indole (7) could be prepared regioselectively by the cyclodehydration of the acetyl derivative of 1. The cyclodehydrogenation was extended to the monosaccharide derivatives of 1. The role of the N-methyl group on the site of annellation has been discussed.