1-Chloro-1,2,4,6-thiatriazine

Chloro-1,2,4,6-thiatriazines (16) readily form the thiatriazinyl radical, for example, on treatment with triphenylantimony. These radicals associate in the solid state to form cofacial dimers (80JOU1303, 85JA1346>. Persistent thiatriazinyl radicals have also been produced by treating chlorothiatriazines with sodium or with triphenylverdazyl (83SUL143>. 

Of the thiatriazines, the 1,2,4,6-system has been the most studied. There has been particular interest in TV-alkyl-1,2,4,6-thiatriazine 1,1-dioxides because of their herbicidal, fungicidal, and histamine H2-antagonist activity (86TL123,87S170). The preparation of l-chloro-l,2,4,6-thiatriazines (576) by reaction of imidoylamidines (575) with an excess of sulfur dichloride was reported (80JOU1303). 

Sulfonyl diisocyanate gives the thiatriazine 778 on treatment with ammonia <1958CB1200>. A convenient and versatile reaction leading to aryl derivatives of l-chloro-l,2,4,6-thiatriazine 779 involves heating an arylamidine with trichlorocyclotrithiazene, (NSCIA in refluxing acetonitrile <1985JA1346>. 

Several 1,2,4,6-thiatriazine 1,1-dioxides have been synthesized from other thiatriazine derivatives by nucleophilic substitution of 3- and/or 5-oxo, -thio, -chloro, -methoxy, -aryloxy, and -thiomethyl by ammonia or amines (84JHC1553 85TL11O1, 85TL1105). Other nucleophilic substitutions have been claimed to give derivatives such as 153 (83GEP3134145), 154 (76CB2107), and 155 (83GEP134141). 

A simple synthesis of 1,3,5-trichloro-l A4,2,4.6-thiatriazine (1) is by treatment of sodium or tetraalkylammonium dicyanamide with thionyl chloride.910 Originally, this reaction was described in 1970 and the product was thought to be jV -chloro-A/-(chlorosulfanyl)-/V-cyano-carboximidic chloride.60 The reaction is carried out with a great excess of thionyl chloride in the presence of a catalytic amount of dimethylformamide. The first reaction step consists of the formation of the thionyl chloride-dimethylformamide complex and reaction with the dicyanamide anion. The second step is a further sulfinylation with elimination of sulfur dioxide.32... 

Chloro-l A6,2,4,6-thiatriazine 1-Oxides from 4//-1,2,4,6-Thiatriazine Oxides... 

Only one example is known of the conversion of 4/f-l, 2,4,6-thiatriazine 1-oxides to the corresponding 1-chlorothiatriazine 1-oxides. Oxidative chlorination of 3-phenyl-5-(trichloromethy 1)-4//-thiatriazine 1-oxide with fer -butyl hypochlorite or /V,/V-dichloroLosylamine gives the corresponding 1-chloro compound 5.47,62 1-Chlorothiatriazine 1-oxides such as 5 are stable crystalline compounds. 

Radicals are obtained from l-chloro-l,2,4,6-thiatriazines reacting with triphenylantimony.61 The solid phase of the radicals exists in the form of a cofacial dimer,48 nitrosyl tetrafluorobo-rate or hexafluorophosphate convert this dimer into the thiatriazinium salts 5. 

The reaction of 3,5-dichloro-A,A-diisopropyl-1 /.4,2,4,6-thiatriazin-l -amine (2) with butyllithi-um gives only dibutyl ketone, probably formed from the ring-transformation product benzoni-trile via butyllithium addition to the ketone imine.45 Reaction of phenylmagnesium bromide with 2 gives 3-chloro-Al,Af-diisopropyl-5-phenyl-lA4,2,4,6-thiatriazin-l-amine (3) in 30% yield.45... 

Chlorine atoms in the 1-position of thiatriazines are readily attacked by secondary amines. Amines with high nucleophilicity and, generally, primary amines cleave the thiatriazine ring system at the endocyclic S - - N bond. Only one case is known in which an excess of secondary amine leads to 1,3-disubstituted thiatriazinamines.28 Even silylated amines react in the first reaction step in the 1-position. 5-Chloro-A,./V-dialkylthiatriazine-l,3-diamines do not react with amines or silylated amines. Compounds of type 2 react selectively with amines to give 1-amino-substituted thiatriazines 3.30,31,47... 

In the 3,5-dichlorothiatriazines 8, one of the remaining chlorine substituents can be displaced by another nucleophile,43 e.g. an amine, to give the corresponding 5-substituted 3-chloro-A,A -dialkylthiatriazin-l-amines 9.30-71 Further substitution, even with silylated amines at moderate temperatures for 24 hours, is not observed. Only with anisidine or toluidine does compound 8a give red unstable trisamino-substituted thiatriazines with R2 = R3 = NHTol,... 

N,AVV, iV -Tetraalkyl-5-chloro-124,2,4,6-thiatriazine-l,3-diamines 9 General Procedure 45... 

Thiolates react in a nucleophilic displacement reaction with 3- and 5-substituted V V-dialkyl-thiatriazin-l-amines 8 or 9 giving alkyl- or arylsulfanyl-substituted A AHdialky thiatriazin-l-amines 16-18. The 3-[alkyl(aryl)sulfanyl]-5-chloro-A,vV-diisopropylthiatriazin-l-amines 17, prepared by an equimolar reaction between the dichloro compound 8 and thiolate, are unstable at elevated temperatures. 

In analogy to the reaction of 3,5-dichlorothiatriazine with thiolates, the same reaction type proceeds with sodium dithiocarbamate (X = S) to yield 3-chloro-Ar,Ar-dialkyl-5-(thiocarb-amoylsulfanyl)-lA4,2,4,6-thiatriazin-l -amines 19a-c as stable crystalline compounds. Further nucleophilic substitution is not observed.45... 

Chloro-5- (diethylamino)thiocarbamoyl]sulfanyl -Ar,yV-diisopropyl-124,2,4,6-thiatriazin-l-amine (19b) Typical Procedure 4S... 

In contrast to dithiocarbamoylthiatriazines vide supra), the reaction of 3,5-dichloro-JV,lV-diiso-propyl-1 A4,2,4,6-thiatriazin-l-amine with piperidinc-1-carbonylthiolate gives the extremely unstable, not isolable 3-chloro-Ar,A -diisopropyl-5-[(piperidinocarbonyl)sulfanyl]-l /4,2,4,6-thia-triazin-1-amine (compound 19d, Section 2.1.1.5.5.3.), which eliminates carbon oxysulfide giving the corresponding 3-chloro-Ar,Ar-diisopropyl-5-piperidino-124,2,4,6-thiatriazin-l-amine.43,45... 

The preparation of l-chloro-l,2,4,6-thiatriazines (51) by reaction of imidoylamidines (50) with excess of sulfur dichloride was reported in 1980 <80JOU1303>. 

Chloro- and fluorosulfonylcarbamoyl chlorides were found to react with aminotriazole (42) to give [l,2,4]triazolo[5,l-c][l,2,4,6]thiatriazine-l,1-dioxide (43) <77JCR(S)238>. A thiazole-fused thia-triazine-dioxide (45) was prepared from the aminothiazole derivative (44) by chloro-sulfonylisocyanate. The observed regioselectivity in this reaction was interpreted by the preference for nucleophilic addition at the more electrophilic isocyanate which was followed by the cyclization at the sulfonyl chloride <87JMC2058>. 

The 3,5-diaryl-l,2,4,6-thiatriazine 1-oxides 47 were converted to the 1-chloro derivatives 140 with sulfuryl chloride (Scheme 18). Treatment of 47 with MCPBA gave the unexpected 1,3,5-triazine product 141 and an unknown byproduct (m.p. >300°C) (Scheme 18). No 1,2,4,6-thiatriazine 1,1-dioxides were isolated. A mechanism for formation of 141 was proposed <2000T7153>. 

Reaction of 36 with 2 equiv of morpholine in toluene gave the 3 -morpholino derivative while treatment of 32 with excess of morpholine afforded 38 <1999IC3022>. Reaction of the 1 A -l-chloro-1 -oxo-l,2,4,6-thiatriazine 163 with diethylamine gave 164 (Equation 12) <2000T7153>. 

Equation 20) - only two examples (X=F, (CF3)2NO) (2) reaction of arylchloromethyl tolyl sulfoxides with S4N4 (Equation 25) - only 3,5-diaryl 1-oxide products, moderate yields, and many by-products (3) displacement of the chloro atoms of l,3,5-trichloro-lX, -l,2,4,6-thiatriazine (Equation (13) Schemes 22 and 25-28). Method (3) is the best and most general recent method, though (to date) restricted to heteroatom-linked substituents at C-3 and C-5. 

Alkyl-2-chloro- and -2-fluoro-sulphonylcarbamoyl chlorides (376), prepared simply from sulphamoyl halides RNHSO2X and phosgene in pyridine/ are useful precursors for the synthesis of 1,2,4,6-thiatriazine 1,1-dioxides, e.g. (377) and (378) (Scheme 85). ... 

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