1.3- Azoles ring synthesis

Tolylaulfonylmethyl isocyanide is a useful and versatile reagent in organic chemistry. It has been used for the synthesis of several azole ring systems by base-induced addition of its C—N=C moiety to various... 

To decrease the reaction time required for the conventional treatment (from 2 up to 48 h) and to improve the conversion level of the reaction, microwave irradiation was successfully applied for obtaining 4-thiazolidinones substituted with azole ring. Siddiqui et al. [174] reported the efficient microwave-assisted solid-supported approach for one-pot diastereoselective synthesis of some analogs of fungitoxic dibenzyles. 

As it has been shown, there are many ways to assemble the 1,4-(oxa/thia)-2-azole ring. Most of them are performed by inter- or intramolecular cyclization of suitable acyclic precursors. Some of them are found to be suitable for the synthesis of various ring systems, by using readily available, and properly modified reactants. Of particular importance are the following (a) the cyclizations of sulfenamides leading to (oxa/thia)azolium salts (Scheme 33) (b) the cyclization of hydroxamic acids (Scheme 39) (c) the dipolar cycloaddition methodology (Scheme 40) (d) the cyclizations of chlorosulfenyl chlorides (Scheme 46) and (e) the cyclizations of chloromethane sulfonamides (Schemes 47 and 48). Other cyclizations reported are preparative ways used mainly for the synthesis of specific compounds and the scope of these reactions has not been widely studied. 

Chimichi et al. have reported the synthesis and spectroscopic data for all four thiazolopyridine isomers in order to examine how the differently substituted fused five-membered heterocycle influences the chemical and spectroscopic properties <1997MRG601>. The unambiguous assignment of the chemical shifts of these systems was reported and coupling constants showed that azole ring fusion on the pyridine system is responsible for a significant... 

Synthesis of pyrido[ 1,2-bJquinazolines through formation of the azole ring from properly substituted quinazoline precursors is also known (61AP556). Thus, the cyclodehydrobromination of the 2-(4-bromo-butyl)quinazolin-4-one (445) with alkali was claimed to give only the linearly annulated 1,2,3,4-tetrahydropyrido[ 1,2-6]quinazolin-4-ones (446) (61AP556). Oxidation of the 3-amino-2-(butyn-l-yl)quinazolin-4-ones (447) with lead tetraacetate led to intramolecular addition of the produced /V-nitrene intermediate to the triple bond to give 449 [86JC S(P 1) 1215]. 

Historically, the first example of l,4-(oxa/thia)-2-azole rings was described by Musante, in the late 1930s, who first correctly suggested the 5-imino-2-phenyl 1,4,2-oxathiazole structure 1 to the product obtained from the reaction of ammonium thiocyanate and benzhydroximoyl chloride <1938G331>. Also, the preparation and some properties of dioxazolones 2 described by Beck should be mentioned <1951CB688>, and also the synthesis of the first nonconjugated dioxazole derivative 3, from hydroxamic acid and benzophenone diethylacetal, described by Exner <1956CLY779>. 

Several reports concerning the synthesis of oxa/thia-2-azole rings by transformations of other heterocyclic rings appeared in CHEC-II(1996) <1996CHEC-II(4)535>. All new reports are classified in accordance with the size of the ring to be transformed. 

The usual ring synthesis route for benzo-l,3-azoles... 

The ring synthesis of the tetrahydro-1,3-azoles is simply the formation of N,N-, N,0-or A, S-analogues of aldehyde cyclic acetals the ring synthesis of the 4,5-dihydro-heterocycles requires an acid oxidation level in place of aldehyde. A good route to the aromatic systems is therefore the dehydrogenation of these reduced and partially reduced systems. Nickel peroxide, " manganese(IV) oxide, copper(II) bromide/ base, and bromotrichloromethane/diazabicycloundecane have been used. The example shown uses cysteine methyl ester with a chiral aldehyde to form the tetrahydrothiazole. 

Similarly to PEG 400 (Scheme 43), glycerol was also found to serve as a good solvent for the azole ring closure thiocarbonylation in the microwave-assisted synthesis of 76 (Scheme 93) [68]. 

H-Benzo[a]carbazole, 4,4a,5,l 1,1 la,l Ib-hexahydro-synthesis, 4, 283 Benzo[b]carbazole, N-acetyl-photochemical rearrangements, 4, 204 Benzo[/]chroman-4-one, 9-hydroxy-2,2-dimethyl-synthesis, 3, 851 Benzochromanones synthesis, 3, 850, 851, 855 Benzochromones synthesis, 3, 821 Benzocinnoline-N-imide ring expansion, 7, 255 Benzocinnolines synthesis, 2, 69, 75 UV, 2, 127 Benzocoumarins synthesis, 3, 810 Benzo[15]crown-5 potassium complex crystal stmcture, 7, 735 sodium complex crystal stmcture, 7, 735 Benzo[ 18]cr own-6 membrane transport and, 7, 756 Benzo[b]cyclohepta[d]furans synthesis, 4, 106 Benzocycloheptathi azoles synthesis, 5, 120... 

Pyrimido[4,5-6]quinolinium salts pseudo bases - ring opening, 3, 208 Pyrimido[4,5-6]quinolinium salts, 4-chloro-hydrolysis, 3, 214 Pyrimido[4,5-6]quinolinones synthesis, 3, 228 Pyrimido[4,5 -6]quinolin-5-ones synthesis, 3, 221-222 Pyrimidothiadi azoles reactions, 6, 533 Pyrimidothiazines synthesis, 4, 527 Pyrimidothiazinones mass spectra, 2, 23... 

The synthesis and chemistry of pyrazoles, imidazoles, and 1,2,3-triazoles were actively pursued in 2006. A review on the cross-coupling reactions on azoles with two and more heteroatoms for pyrazoles and imidazoles has been published <06EJO3283>. Publications relating to 1,2,4-triazole and tetrazole chemistry were not particularly well represented this year. The solid-phase and combinatorial chemistry of these ring systems have not been investigated compared to past years. No attempt has been made to incorporate all the exciting chemistry or biological applications that have been published this year. 

Attempts to directly iodinate quinoxaline failed, and the synthesis of 2,3-diphenyl-5,8-dibromoquinoxaline is somewhat more involved (Scheme 9) [61]. Starting from ort/zo-phenylenediamine, reaction with SOCI2 gives benzothia-diazole in high yield. Bromination in HBr furnishes 4,7-dibromobenzothiadi-azole, which can be alkynylated or directly reduced [62]. Reduction of the dibromide with sodium borohydride leaves the halide substituents unmolested but opens the ring to furnish l,4-dibromo-2,3-diaminobenzene. Reaction of this intermediate with a 1,2-dione furnishes a 2,3-disubstituted 5,8-dibromo-quinoxaline. Pd-catalyzed alkynylation finishes the sequence off and removal of the TMS groups yields the desired 5,8-diethynylquinoxaline monomers (Table 9, entries 13,14). 

The synthesis of fluoroazoles usually involves a chiral epoxide ring opening by the azole, as exemplified by the synthesis of albaconazole (Figure 8.24). 

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