Pyrazolo pyrimidines tautomerism

Pyrazolo[3,4-d]pyrimidine, 4-amino-tautomerism, 5, 310 Pyrazolopyrimidinediones synthesis, 5, 324 Pyrazolopyrimidines acidity, 5, 309 anions... 

Pyrazolopyrimidines, amino-acidity, 5, 309 alkylation, 5, 310 N-oxide synthesis, 5, 324 synthesis, 4, 525 5, 328 Pyrazolopyrimidines, dimethyl-synthesis, 5, 316 Pyrazolo[ 1,5-a]pyrimidines electrophilic attack, 5,311 synthesis, 5, 271, 320, 331 Pyrazolo[ 1,5-c]pyrimidines electrophilic attack, 5, 312 Pyrazolo[3,4- d]pyrimidines nucleophilic attack, 5, 313 synthesis, 5, 161, 272, 323, 334 tautomerism, 5, 309 Pyrazolo[4,3-d]pyrimidines alkylation, 5, 310 synthesis, 5, 272... 

Potentially tautomeric pyrimidines and purines are /V-alkylated under two-phase conditions, using tetra-n-butylammonium bromide or Aliquat as the catalyst [75-77], Alkylation of, for example, uracil, thiamine, and cytosine yield the 1-mono-and 1,3-dialkylated derivatives [77-81]. Theobromine and other xanthines are alkylated at N1 and/or at N3, but adenine is preferentially alkylated at N9 (70-80%), with smaller amounts of the N3-alkylated derivative (20-25%), under the basic two-phase conditions [76]. These observations should be compared with the preferential alkylation at N3 under neutral conditions. The procedure is of importance in the derivatization of nucleic acids and it has been developed for the /V-alkylation of nucleosides and nucleotides using haloalkanes or trialkyl phosphates in the presence of tetra-n-butylammonium fluoride [80], Under analogous conditions, pyrimidine nucleosides are O-acylated [79]. The catalysed alkylation reactions have been extended to the glycosidation of pyrrolo[2,3-r/]pyrimidines, pyrrolo[3,2-c]pyridines, and pyrazolo[3,4-r/]pyrimidines (e.g. Scheme 5.20) [e.g. 82-88] as a route to potentially biologically active azapurine analogues. 

Four NH-tautomeric forms are possible for pyrazolo[3,4-d]pyrimidine (3-6). In the solid state as well as in neutral media this compound was shown to exist as 3. In basic media, the mesomeric anion 300 is the predominant species. In acidic solutions, 301 predominates as the monocation (58JCS2973). 

The tautomeric equilibrium between IH- and 2//-formycin (7-amino-3)8-D-ribofuranosyl-l//-pyrazolo[4,3-d]pyrimidine) has a constant ratio N(2)H/N(1)H = 0.2 and an enthalpy difference estimated at 1 kcal mol". The tautomeric interconversion is catalyzed by (3 x 10 Msec" ) and by OH" (5 X 10 M" sec" ). No other catalytic pathway such as water catalysis or tautomerization via tautomeric cations contributes significantly to the interconversion. Protonation on the pyrazole ring of formycin does not occur significantly (80JA3897). 

The C n.m.r. spectra of formycin, formycin B, and certain pyrazolo[4,3-f/]-pyrimidines have been examined in DMSO and HMPT, and as a function of temperature, in order to probe the prototropic tautomerism of the pyrazole portion of the heterocyclic system. Only the 1-NH % 2-NH prototropic process was observed, and the proportion of the 2-NH tautomer (a higher energy species than the 1-NH tautomer) was shown to depend on the substituent present at C-7 of the pyrimidine portion of the heterocyclic system. 

Acylation and metallation studies on monomers, dimers, trimers, and tetramers containing linked thiophen, pyridine, pyrimidine, furan, benzofuran, benzothiophen, and indole moieties have been published/ Deuteriation, halogenation, and diazo-coupling reactions of 2-oxo- and 2-thioxo-l,2-dihy-dropyrimidinium salts have been studied and compared with results for 2,2-dialkyl-1,2-dihydropyrimidinium and 2,3-dihydro-1,4-diazepinium salts in order to demonstrate the effect of an adjacent 0x0- or thioxo-group on the properties of a 1,5-diazopentadienium system/ Vilsmeier formylation of, and tautomerism in, 2-hydroxypyrazolo[5,l-h]quinazolone and l-phenylpyrazolo[5,l-A]-quinazoline-2,9-dione have been studied/ The pyrazolo[3,4-c]pyrazole (71) has been methylated and acetylated, the major products being (72)/ ... 

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