1,3,4-Thiadiazole 2-dimethylamino

Reaction of a hydrazide (128) with phosgeneiminium chloride (115) led to the 2-dimethylamino-l,3,4-oxadiazole (129) in 90% yield (75AG(E)806). The 1,3,4-thiadiazole system was also obtained in an analogous reaction in which the dithioimidate (130) underwent reaction with the thiohydrazide (131). Depending on the nature of X in (131), the 2-substituent in the resultant 1,3,4-thiadiazole (132) may be varied (80ZC413). Although (130)... 

Tetramethylthiuram disulphide (TMTD) has proved to be a useful reagent for the thiocarbamoylation of amine containing compounds. Thus, reaction of a series of hydrazones of aromatic aldehydes with TMTD in a 1 1 ratio gave amongst other products, 4,4-dimethylthiosemicarbazide 86 and 5-dimethylamino-l,3,4-thiadiazole-2-thiol 85. It was confirmed that 86 was an intermediate in the synthesis of 85 as treatment of 86 with TMTD gave 85 in 85% yield <00RCB344>. 

The last example for the synthesis of this ring system discussed in this section is somewhat different from the previous ones as it presents formation of a positively charged thiadiazolo[3,2-tf][l,3,5]triazinium salt as published by Okide 1994JHC535 the 2 amino 5 alkyl[l,3,4]thiadiazole 167 was reacted with l chloro l,3 bis(dimethylamino) 3-phenyl-2-azaprop-2-enylium perchlorate (a reagent which was synthesized by the same author earlier <1992JHC1551>) to give the quaternary salt 168 in moderate yield (45%) (Scheme 32). 

Ammonium 2,4,6-tris(dioxoselena)hexahydrotriazine-l,3,5-triide Benzo-l,2,3-thiadiazole, 2199 Benzo-l,2,3-thiadiazole 1,1-dioxide, 2191 Bis(S,S-difluoro-N-sulfimido)sulfur tetrafluoride, 4381 Bis(dimethylamino) sulfoxide, 1757... 

Older literature has been reviewed <84CHEC-1(4)545>. The energy barrier to internal rotation of the dimethylamino group in 1,3,4-thiadiazoles is greater by 1.7-2.9 kJ mol than for the corresponding... 

Further extension of this synthesis to guanidines leads to 3,5-diamino-l,2,4-thiadiazoles. Examples are so far confined to the conversion, by the usual procedure, of 2V,2V-disubstituted guanidines into 5-amino-3-dialkyl(or diphenyl)amino-l,2,4-thiadiazoles (66).84,87 In general, this variant of the reaction proceeds less uniformly than with amidines or iso(thio)ureas, and is performed without isolation of the intermediate AT-halogenoguanidines. In some cases (e.g. dimethyl and cyclopentamethylene homologs) the yields are low, and guanidine is formed as a by-product. The 3-dimethylamino homolog (66 R = R ... 

Acetamide replaces a halogen atom (in 166, B = Ph) by the ace-tamido group (50-60% yield), while dimethylformamide yields 5-dimethylamino-3-phenyl-1,2,4-thiadiazole quantitatively.188... 

Acetylation of 5-amino-3-dimethylamino-l,2,4-thiadiazole yields the expected 5-acety-lamino derivative but no product was obtained when sulfonylation was attempted. 3-Amino-5-phenyl-l,2,4-thiadiazole (15 R = Ph) forms the expected derivatives (138), (139) and... 

The alkylated derivative (357) or (356 R = Me) reacts with sodium azide with elimination of sulfur and formation of 3,5-bis(dimethylamino)-l,2,4-thiadiazole (358) in 75% yield (Scheme 129) (71JOC3465). 

Reaction of a hydrazide with dichloromethylene-dimethyliminium chloride (also known as phosgeneimonium chloride) 597 led to the 2-dimethylamino-l,3,4-oxadiazole 598 (Scheme 268) <1973AGE806>. The 1,3,4-thiadiazole 601 was made by an analogous reaction from 599 and 600 (Scheme 269). 

As a rule, oxadiazoles and thiadiazoles are not nitrated. Reports on the production of 2-nitro-5-amino-l,3,4-thiadiazole during the nitration of 2-amino-l,3,4-thiadiaz-ole [274] proved erroneous [275], The compound obtained in this case was 2-nit-ramino-l,3,4-thiadiazole [275], There is only a single paper on the nitration of derivatives of 1,3,4-oxa- and 1,3,4-thiadiazoles [276], 2-Dimethylamino-l,3,4-oxa-and 2-dimethylamino-l,3,4-thiadiazoles react with the nitrating mixture with the formation of 2-dimethylamino-5-nitro derivatives. Aryl-substituted oxadiazoles and thiadiazoles are nitrated in the phenyl ring [277, 278],... 

Thiadiazol 3-Amino-5-dimethylamino- E8d. 136 (3-NH2 - 5-NR2 -1,2,4-dithia-zolium -i-NaN3)... 

The reactions of 3-amino-5-methylisoxazole with l,3-bis-(dimethylamino)-2-azapropene 27 (94JHC535), isocyanate (87JHC501), and trichloromethylsulfenyl chloride (75JOC2600) gave isoxazolo[2,3-a]l, 3.5-triazincs 28, 29, and isoxazolo [3,2-c]thiadiazoles 30, respectively (Scheme 14). 

Flash-vacuum pyrolysis at 550 °C/0.08 Torr of 2-(dimethylamino)-5-phenyl-6//-l,3,4-thiadi-azin-6-ones results in thermal fragmentation with formation of the corresponding N,N-dimethyl-5-phenyl-l,3,4-thiadiazol-2-amine together with dimethylcyanamide and benzo-nitrile.92... 

Similarly, thiazol-2-amine, 5-ethyl-l,3,4-thiadiazol-2-amine, 5-methylisoxazol-3-amine. 1,2,4-triazol-3-amine and benzimidazol-2-amine give the corresponding heterocyclic systems on reaction with 2-aza-l-chloro-l,3-bis(dimethylamino)-3-phenylpropenylium perchlorate.490... 

A comparison, by variable temperature NMR measurements, of the energy barrier to internal rotation of the dimethylamino group in five-membered heterocyclic structures has included the study of 5-dimethylamino-1,2,4-thiadiazole.260 The compound is iso-7t-electronic with 4-dimethylamino-pyrimidine, and is comparable in the positions of its nitrogen atoms. The observed closeness of their energy barriers reflects the analogies between cyclic isosteric compounds in which a sulfur atom replaces a —CH=CH— group. A variety of other aspects opened up by these measurements have been discussed.260... 

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