1.3.4- Thiadiazines, fused

CS607). Compounds 10b and 70 with keto esters afford thiadiazines fused... 

Special mention should be made of bentazone, 3-isopropyl-l//-2,l,3-benzothiadiazin-4-one 2,2-dioxide (74) (Section II,C,2,b) (66GEP1542838). Basagran, the biologically active form of bentazone, is nowadays employed extensively as a selective postemergence herbicide in numerous crops. As already mentioned (Section II,C,2,b), a wide variety of thiadiazines fused to heterocyclic systems have been synthesized in the search for herbicides and success is frequently claimed in the patent literature. 

For the benzo-fused derivative of the parent 1,2,6-thiadiazine 1,1-dioxide, the aromatic tautomer 125a (Scheme 35) was found to be the most stable (82JOC536). 

Tautomeric equilibrium in amino-substituted 1,2,6-thiadiazine 1,1-dioxides fused with five- or six-membered nitrogen heterocycles has been extensively studied by Goya and colleagues. No amino group participation in tautomeric equilibria in these systems has been observed. 

To a mixture of 3.0 grams of N,N -diacetyl-o-anilamide and 20 ml of acetic acid Is added a previously prepared solution of 1.5 grams of chlorine in 31 cc of acetic acid. The reaction mixture is allowed to stand at room temperature for 3 hours and is then evaporated to dryness on a steam bath under reduced pressure. The resulting solid residue is recrystallized from ethanol, yielding the intermediate N,N -diacetyl-2-sulfamyl-4-chloroaniline. The intermediate compound is fused in an oil bath at 250-260°C for 15 minutes, cooled and the product so obtained is crystallized from 80% ethanol yielding 3-methyl-7-chloro-1,2,4-benzo-thiadiazine-1,1-dioxide, MP 330°C. 

Reiter and co-workers found in the course of their extended research on fused [l,2,4]triazines <1994JHC997> that the N-protected methylthiotriazine derivative 110 when reacted with carbon disulfide under strongly basic conditions yields a mixture of two products 111 and 112. When this mixture was treated with dibromomethane, product 113 was easily removed from the reaction mixture, and workup of the mother liquor allowed the isolation of the [l,2,4]triazolo[l,5-c][l,3,5]thiadiazine derivative 114 in 49% yield (Scheme 21). The same authors carried out ring closure of the ring-closed semithiocarbazide 115 to the triazolothiadiazine derivative 118 as shown in Scheme 21 <1997JHC1575>. The starting compound was treated with triethyl orthoformiate. The authors assume that first intermediate 116 is formed which cyclizes to a second intermediate 117 and, finally, ethanol elimination yields the isolated product 118. 

Ring closure to [l,2,4]triazolo[3,4- ][l,3,5]thiadiazines by utilizing the Mannich reaction has been published by a Chinese team <1999SC2027, 2001SC2841, 2001JF1C929> (Scheme 23). 5-Aryl-substituted 3-mercapto[l,2,4]tri-azoles 123 were treated with formaldehyde and primary amines under acidic conditions to yield the fused thiadiazines 124. The reaction was interpreted to proceed via formation of intermediate 125 upon the reaction of 123 with a... 

The compilation of ring systems in Scheme 1 consists of all the ring systems discussed in this chapter. The first three lines of structures are fused oxadiazines, dithiazines, and thiadiazines, these ring systems are followed by various fused... 

For ring closure to //-fused [l,2,4]thiadiazines, two approaches were published during recent years. Chern et al. <1998JME3128> reported that derivatives 186 containing allylamino or allylsulfanyl group in position 3 of the... 

Two different c-fused [l,2,4]thiadiazines were synthesized nearly at the same time, and the syntheses are shown in Scheme 30. Boverie et al. <2001JPL973> reported a procedure for the imidazole ring closure, which is fairly... 

More intensive investigations have been carried out with synthesis of t-fused [l,3,5]thiadiazines, and the transformations are shown in Scheme 32. 

The synthesis of this ring system by condensation of 3,4,5-triamino-l,2,6-thiadiazine-l,1-dioxide with formic acid equivalents to give the fused imidazole ring dates back to the review by Montgomery and Secrist <1984GHEC(5)607>. This methodology was extended to cyclocondensation reactions of 3,4,5-triamino-l,2,6-thiadia-zine-1,1-dioxide with electrophiles such as methyl chloroformate and carbon disulfide to yield 6-oxo 98 and 6-thioxo 99 derivatives of 4-aminoimidazo[4,5-d-l,2,6-thiadiazine-2,2-dioxide respectively (Scheme 72) <1999BMC1617>. 

Functional derivatives of 1,3,4-thiadiazines and of fused systems on their base, synthesis and properties 91KGS1443. 

The same type of synthesis affords pyrazino[2,3-e]-1,2,4-triazines (329) and (330) from the diamino precursor (328), by reaction of the latter with glyoxal or phenylglyoxal, respectively. Product (329) is a dihydrate. The fully aromatic intermediate could not be isolated. Formation of (330) involves not only covalent solvation, but also an unusual TV-methylation of the presumed first-formed intermediate, and the suggested mechanism is outlined in Scheme 24 <86JHC33,93H(36)2577>. Reversing the order of polarities of the components allows [4 + 2] cyclization of pyrimidine (331) with orr/io-phenylenediamine (332), giving the benzo fused pyrazino[2,3-c][l,2,6]thiadiazine (333) (a [l,2,6]thiadiazino[3,4-6]quinoxaline]) (Equation (52)) <72ZN(B)1471>. 

Bifunctional nucleophilic compounds can add to TV-alkylpyrazinium salts, and the benzo fused pyrazino[2,3-e][l,3,4]thiadiazine (471) as well as the benzo fused pyrazino[2,3-e]-l,2,4-oxadiazine (472) can be made by this method (Scheme 40). A closely related reaction is exemplified by the preparation of the pyrazino[2,3-e]-1,2,4-triazine (473) (Equation (94)) <87KGS557, 87KGS1118). The pyrimido[5,4-c][l,2,5]oxadiazine (475) can be prepared by treatment of the uracil derivative (474) with isoamyl nitrite (Equation (95)). Presumably the reaction proceeds by cyclization of an initially formed 5-nitrosopyrimidine intermediate (64ZC454). 

JCS(P1)1747>, and also the benzo fused pyrazino[2,3-< ][l,3,4]thiadiazine (500) (Equation (106)) <89JIC124>, more properly named as a thiadiazine[5,6- ]quinoxaline. 

Reaction of pyridine-derived aminosulfonamides 489 and 491 with urea or guanidine gives access to the fused 1,2,4-thiadiazine 1,1-dioxides 490 (Scheme 256) and 492 (Scheme 257), respectively <1999T5419, 2002JME90, CHEC-III (9.05.9.2.3)331>. 

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