Triazolo isomers

Amino-l,2,4-triazole undergoes a cyclocondensation with 3-etlioxyacrolein (7) to form 1,2,4-triazolo[l,5-a]pyrimidine (3) or its [4,3-u] isomer (5), according to whether it reacts as IH or 4H tautomer 2 or 4. Moreover, the pyrimidines 3 and 5 can interconvert by a Dimroth rearrangement. Since the H NMR spectrum 30a does not enable a clear distinction to be made AMX systems for... 

Assignment of the l,2,4-triazolo[l,5-c]pyrimidine structures to the products obtained from the previously described cyclizations and not the alternative [4,3-c] structures has been rationalized and corroborated on the basis of (a) preference of cyclization at the more nucleophilic triazole ring N2 rather than at its less nucleophilic N4 (65JOC3601 88JMC1014), (b) inability of the obtained products to undergo acid- or base-catalyzed Dimroth rearrangement, a property characteristic of the thermodynamically less stable [4,3-c] isomers (91JMC281), (c) comparison with unequivocally prepared... 

Similar to their [4,3-c] isomers [99AHC(75)243], 1,2,4-triazolo [l,5-c]pyrimidiiies displayed numerous biological and medicinal activities. In addition, the [1,5-c] isomers found useful agrochemical applications as herbicides. 

Treatment of 3-diazo-3//-[ 1,2,4]triazole with 1-morpholinocyclohexene or 1-piperidinyl cyclohexene gave triazolotriazine 818 (87JOC5538), and with 1,1-dimethoxyethane afforded a mixture of two isomers of triazolo[3,4-c]triazine 819 and triazo)o[5,l-r]triazine 820, respectively [90JCS(P2)1943]. Compound 819 was the major product and it converted on storage to 820 (Scheme 165). 

Nitration of a series of mesomeric betaines was extensively studied in connection with their potential use as explosives (Scheme 3). Nitration of l,2,3-triazolo[2,l- ]benzotriazole 74 can be achieved selectively, occurring first at the 7-position which is followed by nitration at the 3- and 5-positions. Thus, nitration with 45% nitric acid gives a mixture of 7-nitro derivative 75 (39%) and dinitro derivative 76 (58%), while 70% nitric acid yields a mixture of 3,7- (52%), 5,7- (23%), and 3,5-dinitro (5%) isomers 76-78. Clean trinitration to 3,5,7-trinitro-l,2,3-triazolo[2,l- ]benzotriazole 79... 

Alkylation or acylation takes place at the nitrogen in position 1 when l/7-[l,2,4]triazolo[4,3-A][l,2,4]triazole 9 is treated with methyl iodide or acetyl chloride, furnishing compound 10 or 11, respectively <1983S415>. The 7-methyl isomers 13 are obtained after conversion of compounds 9 into the 1-acetyl derivatives 11 followed by methylation with methyl trifluoromethanesulfonate to give the l-acetyl-6-aryl-7-methyl-3-methylthio-17/-[l,2,4]triazolo[4,3-A]-[l,2,4]triazol-7-ium-trifluoromethanesulfonates 12, which upon treatment with aqueous sodium carbonate afford the 7-methyl derivatives 13 <1985BCJ735>. 

Wiench et al. investigated chemical shifts of a set of positional isomers of azaindolizines <1994MRG373>. In Table 3, 13C and 1SN NMR chemical shifts of two related ring systems, the unsubstituted [l,2,4]triazolo[l,5- ]-pyrimidine A and [l,2,4]triazolo[3,2- ]pyrimidine B, are compared. 

Thermal cyclization of 3-guanidino-2,4-thioxoquinazoline (320) gave 2-amino-5-thioxo-l,2,4-triazolo[l,5-c]quinazoline (321) (80PHA582) the corresponding linear isomer, which might have been obtained through the... 

R1 = R2 = H) gave the triazolo[l,5-a]pyrimidines (125), but with 124 (R1 = R2 = Me) afforded the dioxo derivative 126, and with a-cyano- y-butyrolactones (127) or 2-amino-3-ethoxycarbonyl-5,6-dihydro-4//-thiopyran (129) gave the triazolopyrimidines 128 and 130, respectively (81JHC1287). Treatment of 4-ethoxymethylene-2-phenyl-5(4//)-oxazolone (131) with 5-amino-3-methylthio-l//-1,2,4-triazoles gave the triazolo[l,5-a]pyrimidi-none 132 and the [4,3-a] isomer 133 (93H955) (Scheme 24). 

Synthesis of copper and zinc complexes of 5,7-dimethyl-l,2,4-triazolo [l,5-a]pyrimidine has been reported [93AX(C)1902 94AX(C)510], Reaction of copper(II) thiocyanate with 5,7-dimethyl-l,2,4-triazolo[l,5-a]-pyrimidine (l) gave three different complexes two isomers of [Cu(NCS)2L2]2 and Cu(NCS)2L2 H20 (84IC2803). The mononuclear complexes, bis(thiocyanato-N)bis(6-methyl-l,2,4-triazolo[l,5-a]pyrimidine-jV-3)copper(II) and the polynuclear pseudo-layered complexes, bis(thio-cyanato-A0bis(5-methyl-l,2,4-triazolo[l,5-a]pyrimidine-A -3)copper(II) were prepared (89POL2313). 

C-Alkyl-l,2,4-triazolo[4,3-a]pyrimidines are distinguished from their respective [l,5-a]isomers by their UV absorption at longer wavelength. The UV spectra (at pH 2 and pH 10) have been used to differentiate the isomeric 5- and 7-hydroxy-l,2,4-triazolopyrimidines this differentiation may be confirmed by the IR stretching frequency of the CO group. The isomeric A-alkyl-l,2,4-triazolopyrimidines are more readily distinguished by their IR spectra (68T2839). H and 13C NMR and UV spectroscopy have been... 

Cyclization of 5-methoxy(nitro)-4-hydrazinopyrimidines (485) with tri-ethyl orthoformate gave the l,2,4-triazolo[4,3-c]pyrimidine intermediate 486, which cannot be isolated due to its conversion to its [1,5-c] isomer 487 by a Dimroth rearrangement. However, the 5-benzyloxypyrimidine derivative, under the same conditions, afforded a mixture of the 8-benzyloxy derivatives of both [4,3-c] and [l,5-c]isomers 486 and 487, respectively (86TL3127 89JHC687 90H277) (Scheme 95). 

Apparently triazolo[4,3-c]pyrimidine rearranges readily into the more stable isomer triazolo[l,5-c]pyrimidine. A detailed study on related systems showed that electronic and steric factors are mainly responsible for this rearrangement (78AJC2505 90T3897 92KGS225) (Scheme 102). 

Reaction of 4-chloro-5-methyl-6-phenyl-2-pyrimidinamine (566) with formylhydrazine yielded a mixture of triazolo[4,3 c]pyrimidine (567) and its [l,5-c]isomer 568 (83USP4405780), and boiling 566 with formylhydrazine in DMF containing a 3-A molecular sieve afforded 567 (81GEP3029871) (Scheme 110). 

The rearrangement of the triazolo[4,3-c]pyrimidines, e.g., 24, to their [2,3-c) isomers has been hypothesized as going through a neutral covalent hydrate followed by ring fission.35 Kinetic evidence has been... 

Dissolution of 7V-[3-phenyl-5-(l,2,4-triazolyl)]benzohydrazonoyl bromide hydrobromides 183 in 80% acetone-water (v/v) at 0°C yielded the [1,2,4]triazolo[3,4-c]-l,2,4-triazole 184 and the hydrazide 185 (65TL841). However, solvolysis of 183 in the presence of base at low temperature yielded a mixture of 184 and their isomers 186 (65TL841). 

A number of novel fused 1,2,4-triazole were reported and these include [l,2,4]-triazole[l,3]-thiazinoquinolines (118, 119) and their positional isomers [95MI297], The electrocyclization of N-aziridinylimino carbodiimides generated by dehydration of urea (120), produces 5,6-dihydro-7H-imidazol[l,2-b][l,2,4]triazoles (121) and 5,6-dihydro[l,2,4]triazolo[5,l-t/]-[l,3,5]oxadiaze-pines [95TL2815], The mechanisms of each transformation is discussed. 

The condensation of 3-(substituted)-l,2,4-triazoles with an A-cyanocarbonimidate at high temperatures gives (1,2,4]triazolo 1,5-a [ 1,2,3]triazines (34) which are converted to other such products by standard metatheses. At lower temperatures l,2,4Jtriazolo[4,3- ][l,3,5]-triazines (35) can also be obtained which rearrange to the more stable (1,5-a] isomers on heating. Cyclisation of the hydrazides (36) also leads to [1,5-a] fiised triazines (Scheme 20) [95JCS(P1)801],... 

Methylation of 7-amino-l,2,3-triazolo[4,5-d]pyrimidine (8-azaadenine) (140) with dimethyl sulfate afforded the N-3 and N-9 methylated isomers 141 and 142, respectively, which upon further methylation with methyl iodide or benzenesulfonic acid methyl ester gave 3,7- and l,9-dimethyl-8-azaadeninium salts 144 and 145, respectively. Thermal decomposition of the dimethyl derivatives led to a transmethylation to give 6-methylamino-9-methyl-8-azapurine (143), whose methylation afforded 1- and 7-methyl-6-methylamino-9-methyl-8-azapurinium salts 146 and 147 (80ZOR2204) (Scheme 28). 

The amination of 5-phenyl-l,5-dihydro[l,2,3]triazolo[4,5- /]-l,2,3-triazole (31) with o-(mesityl-sulfonyl)hydroxylamine afforded two V-aminated products distinguishable on the basis of their l3C NMR spectra (Equation (1)). The major product (46%), showed one carbon signal other than those from the phenyl ring and was therefore assigned as the symmetrical 2-amino derivative (32). The minor product showed two l3C signals in addition to those from the phenyl ring and was believed to be represented by structure (33) or (34) (33) is the preferred isomer on the basis of the similarity of its NMR spectrum to that of known l-acetyl-5-phenyltriazolotriazole. 

---