2,1,3-Benzothiadiazol-2,2-dioxid

Friedel-Craft acetylation of385 followed by bromination yields 5-(2-bromoacetyl)-1,3-dibenzyl-1H, 3H-2,1,3,-benzothiadiazole-2,2-dioxide (387). Reaction of 387 with N-benzylated amines followed by reduction with hydrogen produces (388). No significant increase in heart rate, blood pressure, left ventricular pressure and bronchodilator activity was observed when the thiadiazoles 388 were tested in dogs. 

The 1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxides (376 R=H,Me,Cl) react with cyclohexylamine to give (R1NH)2S02 (R1=cyclohexyl). 

The title other methods does not mean that these methods are unimportant, but rather includes a few specific approaches to the synthesis of biaryls. First of these involves the benzynes as reactive species, capable to react with a number of arenes, including themselves, to give the respective biaryls in various yields [94-97]. As the benzyne precursors, benzenediazonium carboxylate (59a) [94], diphenyIiodonium-2-carboxylate (521) [96], benzothiadiazole dioxide (522), and 1-aminobenzotriazole (523) have been used. More conveniently, the benzynes have been in situ generated upon the treatment of anthranilic acid (58) with alkyl nitrites (via 59a), Scheme 50. 

Another heterocyclic molecule that can serve as a benzyne precursor is benzothiadiazole-1,1-dioxide, which decomposes with elimination of sulfur dioxide and nitrogen. ... 

C. 1,2,3-Benzothiadiazole 1,1-dioxide. Caution 1,2,3-Benzo-thiadiazole 1,1-dioxide in the solid slate can explode spontaneously, particularly on being warmed, jolted, or scratched. For most purposes it need not be isolated, but can be used in solutions, which are relatively safe. Any operations involving the solid material should be done very carefully, using good shielding. 

Benzothiadiazole 1,1-dioxide slowly decomposes even at 0°, hence it should always be used on the day on which it is made. For most purposes it is not necessary to isolate the dioxide the ether solution can be used, or solutions in other solvents can be prepared by adding the other solvent and distilling off the ether under reduced pressure (bath temperature 0°). In this way larger amounts of the dioxide than are described in this procedure can be handled without danger. 

Benzothiadiazole 1,1-dioxide can be conveniently assayed and characterized without isolation by forming its adduct with cyclopentadiene.5 The following procedure illustrates characterization, for assay the same procedure can be applied to an aliquot, with all amounts scaled down in proportion. The dried ether extract of 1,2,3-benzothiadiazole 1,1-dioxide prepared from 1.43 g (0.0080 mole) of sodium 2-aminobenzene-sulfinate is concentrated to about 20 ml at 0°, and 20 ml. of acetonitrile at —20° is added. Twenty milliliters of cold, freshly prepared cyclopentadiene6 is added The mixture is kept overnight at —10° to 0°. Solvent and excess cyclopentadiene are removed by evaporation at 0° under reduced pressure to leave 1.20-1.28 g. (64-68% based on sodium 2-aminobenzenesulfinate) of crude 1-1 adduct, mp. 87° (dec.). For purification it is dissolved in 20 ml. of methylene chloride, 70 ml. of ether is added, and the solution is kept at —70°. Adduct decomposing at 90° crystallizes recovery is about 75%. From pure, crystalline 1, 2, 3-benzothiadiazole 1,1-dioxide the yield of adduct is 92-98%. 

Purer product can be obtained by reducing 1,2,3-benzothiadiazole 1,1-dioxide with zinc and acetic acid to 1,2,3-benzo-thiadiazoline 1,1-dioxide, which is oxidized back with lead tetraacetate.5... 

Benzothiadiazole 1,1-dioxide has been prepared only by the present method.5... 

Benzothiadiazole 1,1-dioxide decomposes smoothly in solution at 10° to give dehydrobenzene ( benzyne ), nitrogen, and sulfur dioxide.5,7 In this way, as well as by the thermal... 

Addition, acetic acid to bicyclo[2.2.1]-hepta-2,5-diene to give nortri-cyclyl acetate, 46, 74 1,2,3-benzothiadiazole 1,1-dioxide to cyclopentadiene, 47, 8 benzyne to tetraphenylcyclopentadie-none, 46,107 Br, F to 1-heptene, 46,10 carbon tetrachloride to olefins, 46, 106... 

Benzophenone 46, 36 solvent for Diels Alder reactions at elevated temperatures, 46, 44 1,2,3 Benzothiadiazole 1,1 dioxide, 47,4... 

Compounds of special interest whose preparation is described include 1,2,3-benzothiadiazole 1,1-dioxide (a benzyne precursor under exceptionally mild conditions), bis(l,3-diphenylimida-zolidinylidene-2) (whose chemistry is quite remarkable), 6- di-melhylamino)julvene (a useful intermediate for fused-ring non-benzenoid aromatic compounds), dipkenylcyclopropenone (the synthesis of which is a milestone in theoretical organic chemistry), ketene di(2-melhoxyethyl) acetal (the easiest ketene acetal to prepare), 2-methylcyclopenlane-l,3-dione (a useful intermediate in steroid synthesis), and 2-phenyl-5-oxazolone (an important intermediate in amino acid chemistry). 

It is known that benzenediazonium-2-carboxylate decomposes to give benzyne via the zwitter-ion (128) 161>. We therefore checked that benzyne is involved in our reactions by carrying out reactions with cinnamaldehyde using benzyne generated from benzothiadiazole-1,1-dioxide 162), diphenyhodonium-2-carboxylate i 3,164)( weil as fr0m anthranilic acid165). Flavene was isolated from each reaction and hence our reactions do involve aiynes and are not arynoid 13 8). 

Diamino-2,l,3-benzothiadiazole 82 affords [l,2,5]selenodiazolo[3,4-i ]-2,l,3-benzothiadiazole 83 quantitatively on treatment with selenium oxychloride in refluxing chloroform-pyridine <2004JHC955>. This was an improvement of the previous method using selenium dioxide (62% yield) <1984ZNB485>. 6-Isoprenyl-477-imidazo[4,5-< ]-benzothiadiazolone 84 was obtained when 4,5-diaminobenzothiadiazole was reacted with methyl acetoacetate in xylene at reflux (Scheme 10) <1997H(45)19>. 

Somewhat less common is the preparation of the analogous. S -oxidcs and. S, .S -dioxidcs. Recently, l,3-dihydro-2,l,3-benzothiadiazole 2,2-dioxides 201 <1999JA10281> and 202 <2004BML5045> were prepared from the corresponding 1,2-diamines using sulfamide (Equation 44). 

Cyclopentadiene, adduct formation with 1,2,3-benzothiadiazole 1,1-dioxide, 47, 8... 

The electronegative influence of the thiadiazole system greatly increases the acidity of substituents (Table 2). The effect is further enhanced in the 1-monoxide and 1,1 -dioxide analogues. The ionization constants of 4- and 5-hydroxy-2,l,3-benzothiadiazoles were determined in water <70AC(R)80l>. 

Photolysis of 2,1,3-benzothiadiazole-l-oxide produces l,3-dihydro-2,l,3-benzothiadiazole-2,2-dioxide, shown by flash photolysis to be formed via hydration of the 2-oxide intermediate... 

The syntheses from [4+1] atom fragments, in which the Group 16 heteroatom is introduced between two nitrogen atoms, are the most widely applicable and versatile methods available for construction of the 1,2,5-thiadiazole ring system. These methods have been applied to the synthesis of monocyclic and polycyclic aromatic forms of these ring systems in addition to the direct formation of 1-oxides and 1,1-dioxides, 2-oxides, quaternary salts, and reduced forms. The earliest use of the [4+ 1] synthesis dates back to 1889 when Hinsburg prepared 2,1,3-benzothiadiazole (I) from o-phenylenediamine and sodium bisulfite. 

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