4-Amino-1-arylpyrazole durchThorpe-Cyclisierung

Microwave-assisted preparation of 4-amino-3-cyano-5-methoxycarbonyl-N-arylpyrazoles as building blocks for the diversity-oriented synthesis of pyrazole-based polycyclic scaffolds

“…15 Condensation of 1,3-diketones with hydrazine derivatives, known as the Knorr reaction ( path a, Scheme 2) [16][17][18] or 1,3dipolar cycloaddition of nitrile imines with alkynes ( path b, Scheme 2) [19][20][21] are the most popular methods. [23][24][25][26] Although this latter strategy appears highly attractive, very few examples have been reported and, due to the poor yields observed, its scope has never been fully explored. [23][24][25][26] Although this latter strategy appears highly attractive, very few examples have been reported and, due to the poor yields observed, its scope has never been fully explored.…”

“…[23][24][25][26] Recently, phase-transfer conditions were used to improve the yield and shorten the reaction time to 2-2.5 h. 29 With the same objective, we were wondering whether this Thorpe-Ziegler cyclization could be further optimized owing to microwave activation ( Table 2). According to previous reports, cyclization occurs with activated methylene reagents (ethyl or methyl bromoacetate, chloroacetonitrile) under basic conditions (K 2 CO 3 , TEA) in DMF at 90°C within 6-7 h to give the corresponding aminopyrazole in 22-80% yield.…”

“…In the particular case of 4-amino-3-cyano-N-arylpyrazoles (R 2 = CN, R 3 = NH 2 , R 4 = EWG), the access to the pyrazole ring involves a Thorpe-Ziegler cyclization 22 of dicyanohydrazone intermediates with activated methylene reagents ( path c, Scheme 2). [23][24][25][26] Although this latter strategy appears highly attractive, very few examples have been reported and, due to the poor yields observed, its scope has never been fully explored. Our first goal was therefore to re-investigate this Thorpe-Ziegler reaction in order to develop a general and efficient method allowing the access to the targeted 4-amino-3-cyano-N-arylpyrazoles.…”

“…According to previous reports, cyclization occurs with activated methylene reagents (ethyl or methyl bromoacetate, chloroacetonitrile) under basic conditions (K 2 CO 3 , TEA) in DMF at 90 °C within 6-7 h to give the corresponding aminopyrazole in 22-80% yield. [23][24][25][26] Recently, phase-transfer conditions were used to improve the yield and shorten the reaction time to 2-2.5 h. 29 With the same objective, we were wondering whether this Thorpe-Ziegler cyclization could be further optimized owing to microwave activation (Table 2). It is now well established that microwaves can greatly speed up reactions, thus lowering any possible degradation, and consequently improve the overall yield.…”

Substituted 3,4‐Diamino‐thieno[2,3‐b]pyrroles

“…C 50,48 H 4,89 N 13,59 S 10,32 Gef. C 50,59 H 5,03 N 14,20 S 10,19 IH-NMR (DMSO-d,), 6 = 5,50 (s, 3H, CH,); 5,67 (s,3H,CH,);4,33 (8, 2H, CH,); 4,0 (m, 2H), 4,06-6,06 (m, 3H, Allyl-H); G,57 ppm (s, 2H, NH,). 3a aus 'La: I n einer Losung von 0,l g Na in 20 ml abs.…”