Application of Azide-Tetrazole Tautomerism and Arylsulfanyl Group Dance in the Synthesis of Thiosubstituted Tetrazoloquinazolines

Abstract

Nucleophilic aromatic substitution reaction between 4-aryl­thio-2-chloroquinazolines and NaN3 takes place with an unusual sulfanyl group dance and leads to the formation of 5-(arylthio)tetrazolo[1,5-c]-quinazolines, which do not form the azide tautomer and do not undergo CuAAC reactions with alkynes. On the other hand, 5-azidotetrazolo[1,5-a]quinazoline (formally described as 2,4-diazidoquinazoline) undergoes regioselective nucleophilic aromatic substitution with thiols at C5 and forms 5-(alkyl/arylthio)tetrazolo[1,5-a]quinazolines, the structure of which has been proved by X-ray crystallography. The latter exist in tautomeric equilibrium with their 2-azidoquinazoline form, which provides possibility for copper-catalyzed azide–alkyne 1,3-dipolar cyclo­addition reaction, leading to the 4-alkyl/arylthio-2-(1H-1,2,3-triazol-1-yl)quinazolines.

SnAr Reactions of 2,4-Diazidopyrido[3,2-d]pyrimidine and Azide-Tetrazole Equilibrium Studies of the Obtained 5-Substituted Tetrazolo[1,5-a]pyrido[2,3-e]pyrimidines

“…Indeed, SNAr reactions in 2,4-diazidopurines V [21][22][23] and deazapurines VI [24,25] take place at the C-2 position (Figure 1c). However, this is not the case with quinazoline VII [26,27] and pyrido [2,3-d]pyrimidine VIII [28], where a conventional C-4 addition is observed.…”

“…13 Methanolic ammonia (100 µL, w = 25%) was added to a solution of 2,4-diazidopyrido [3,2d]pyrimidine (2) (50 mg, 0.235 mmol, 1 eq) dissolved in DCM (1 mL) in a 10 mL glass vial and reaction mixture was stirred overnight. After the reaction completion (HPLC monitoring), crude mixture was evaporated under reduced pressure and crystallized from pyridine to yield brown crystals (27 Cyclopentanol (24 mg, 0.28 mmol, 1.2 eq) was added to 2,4-diazidopyrido [3,2-d]pyrimidine (2) (50 mg, 0.23 mmol, 1 eq) and K 2 CO 3 (39 mg, 0.28 mmol, 1.2 eq) solution in MeCN (1 mL) under a N 2 atmosphere and the resulting reaction mixture was stirred at 80 • C for 3 days. Water (10 mL) was added to the reaction mixture and extracted with DCM (3 × 5 mL).…”

Regioselective quinazoline C2 modifications through the azide–tetrazole tautomeric equilibrium

“…While arylsulfanyl group rearrangement reactions have been documented by us for modifying 2,4-substituted quinazolines [ 17 – 18 ], and sulfonyl group rearrangement has been applied to functionalize purines [ 19 ], the literature lacks information on sulfonyl group migration in quinazolines. Notably, this transformation has not been previously reported, despite its potential utility in the synthesis of drugs such as terazosin and prazosin [ 20 ].…”

2,4,6,8-Tetraazidopyrimido[5,4-d]pyrimidine: a novel energetic binary compound

“…Recently, our group has developed several novel synthetic methodologies for functionalization of fused pyrimidines, exploring the synthetic utility of azide as a functional group and azide-tetrazole tautomeric equilibrium thereof. [17][18][19][20][21][22][23] While studying diazidopyridopyrimidines, 24,25 we ought to design a similar heterocyclic azide with explosive properties.…”