Pyrazolo thiazoles

The 2-thienylthiourea (245) on oxidation with bromine in acetic acid gave the thieno[3,2-djthiazole (247). It has been suggested that the intermediate electrophilic sulfenyl bromide adds to the 2,3-bond of the thiophene ring to form (246) when then loses HBr to give (247) (71AJC1229, 78JHC81). Pyrazolo(3,4- /]thiazoles are formed in a similar fashion (76GEP2429195). 

The synthesis of pyrazolo[4,3-rf]-l,2,3-triazine starting from a pyrazolo-3-carbaldehyde derivative has been reported <00JIC168>. Azolo-l,2,4-triazine derivatives have been prepared via the reaction of functionalized thiazole derivatives with several heterocyclic diazonium salts <00JCR(S)206>. The reaction of 1,2,4-triazolium salt 67 with alkene 68 gives the pyrrolo[2,l-/][l,2,4]triazine 69 <00H(53)213>. 

Oxidation of sulfur atom of pyrazolo[l,5-c]thiazole 64 into sulfoxide 65 followed by Pummerer-type dehydration furnished the transient nonclassical pyrazolo[ 1,5-c]thiazole, the thiocarbonyl ylide 67, which could react with various dipolarophiles such as Ar-pheny 1 ma 1 eiinide (Equations 27 and 28) <2000T10011>. In an excess of oxidizing agent, pyrazolo[l,5-c]thiazole 64 was readily converted to sulfone 66 (Equation 27) <2001J(P1)1795>. 

Acetic anhydride-promoted ring-closure reaction of 2-phenylimino-thiazoles 259 and 2-amino-benzoimidazolium salts 261 give the corresponding imidazo[2,l+]thiazolium 260 and imidazo[l,2- ]benzimidazole 262 compounds (Equations 114 and 115) <1997CHE728, 1999PCJ361 >. A similar cyclocondensation was reported for the elaboration of pyrazolo [l,5- ]benzimidazoles <2004RJ0221>. 

A tandem reaction between ethyl 1-pyrazolacetate 282, carbon sulfide, and iodomethane was developed for the preparation of pyrazolo[5,l+]thiazole derivatives 283 (Equation 124) <2000SC763>. 

Aminorhodanines 284 reacted with ethyl 2-bromo-3,3-diethoxypropionate to provide 2,3-dihydro-pyrazolo[5,1 -b -thiazoles 285. The mechanism proposed for the cyclization involved via a sequential condensation-sulfur extrusion reaction (Equation 125) <1994JHC1719>. 

Heating 4-azidothiazoles having an imino or aldehyde group at the 5-position affords fused pyrazolo- and isoxazolo[3,4-d]thiazoles (Equation (7)). When an alkenyl group is in 5-position of the triazole ring, 4//-pyrrolo[2,3-[Pg.454]

The 2-thienylthiourea (287) with bromine in acetic acid gives the thieno[3,2-d]thiazole (288) (71AJC1229,78JHC81). Pyrazolo[3,4-t/Jthiazoles are formed similarly (76GEP2429195). 

As shown in Scheme 8, a common ketone precursor led to the pyrazolo[4,3- ]- and thiazolo[5,4- ]-fused 1,4-benzoxazines (96) and (97) <87JMC580>. For the synthesis of compound (96) the ketone was condensed with HC02Et and subsequently cyclized with hydrazine. For the synthesis of the thiazole (97) a-bromination of the ketone was followed by condensation with thiourea. The linear tricyclic structures (96) and (97) were supported by H and 13C NMR spectroscopic analyses. 

The method has been used to prepare pyrrolo[2,1 -6 ]thiazoles, pyrrolo[ 1,2-a]imidazoIes, pyrrolo[l,2-6]triazoles, li/-pyrazolo[l,5-6]imidazoles, imidazo[2,l-6]thiazoles, imi-dazo[2,1 -b 1,3,4]oxadiazoles, imidazo[2,1 -b 1,3,4]thiadiazoles, imidazo[2,l-6]-... 

The sulfenyl bromide would add to the 2,3-bond followed by elimination of HBr. The method has been used for the preparation of thieno[3,2-d]thiazoles (78JHC81) and pyrazolo[3,4-d]pyrazoles (76GEP2429195) (equation 58). 

---