Sulfonyl isocyanates

Instead of amines, sulfonamides have also been used as starting materials, producing the highly reactive sulfonyl isocyanates, which have found apphcations in the manufacture of dmgs for diabetics and as drying agents (qv) (4,9,16). 

Tertiary amines have been shown to react with isocyanates ia an analogous fashion to form ureas (41—43). Similarly, a2iridines (three-membered rings containing nitrogen) are found to react with isocyanates to yield cycHc ureas. Tertiary amines have also been shown to form labile dipolar 1 1 adducts with isocyanates reminiscent of salt formation. In contrast, formaldehyde acetal aminals form iasertion products with sulfonyl isocyanates (44,45). 

A large number of Diels-Alder-type reactions, involving both aromatic and sulfonyl isocyanates, have been reported. Heterodienes having high electron density ate found to add to isocyanates to form sis membered heterocycles as shown in Figure 2 (48—50). 

Fig. 2. Diels-Alder-type reactions of aromatic and sulfonyl isocyanates.

Reductive ring opening of the [i-lactam 10 (X = O), obtained by [2 + 2] cycloaddition of chloro-sulfonyl isocyanate and tetraphenylcyclopentadiene followed by treatment with /7-cresol, with sodium hydride in anhydrous tetrahydrofuran yields 3,5,6,7-tetraphenyl-2//-azepin-2-one (11, X = O).41 Surprisingly, similar treatment of the reduced /Mactam 10 (X = H2) is reported to yield 3,5,6,7-letraphenyl-2//-azepine (11, X = H2), the first monocyclic 277-azepine to be isolated and characterized. Physical data for this compound, however, are inconclusive and attempts to reproduce this synthesis have failed.291... 

Because of their many side reactions, sulfonyl isocyanates, and especially the highly reactive chlorosulfonyl isocyanates, have been only sporadically employed (21HCA861). 

This reaction is typical for the synthesis of sulfonylureas it is mildly exothermic and proceeds smoothly in a variety of inert aprotic solvents. The product is usually obtained in very high yield, as a fine crystalline precipitate. The sulfonyl isocyanates are readily prepared from the substituted benzene sulfonamides by reaction with phosgene, Fig. 3, in the presence of an alkyl isocyanate, for example, butyl isocyanate in an inert solvent at 120 to 140°C according to the general procedure of H. Ulrich and A. A. R. Sayigh (Ref. 3). 

When the dramatic improvement in activity was found with the 4,6-dimethylpyrimidine heterocycle, sulfonylureas of this system were prepared from the three isomeric tolyl sulfonyl isocyanates. The para compound, which was a literature compound (Ref. 9), was devoid of activity whereas, the meta compound was found to have substantial activity. When the ortho tolyl compound was prepared, another major boost in activity was observed (Figure 10). 

Thioxo-1,2,4-dithiazolidines can be obtained from thioxo-l,2,4-thiadiazolidines by Dimroth rearrangement (Scheme 47) or reversibly by addition and elimination of acetone (Scheme 22). 1,2,4-Dithiazole type products are also obtained from thiocarbonyl isothiocyanates (154) by reaction with CI2 <84CHEC-I(6)897>, PhMgBr, Sj, or CS2. Other routes include reactions of carbonyl isothiocyanates and thiocarbonyl isocyanates with P4S10 or Sg <84Chec-I(6)897> and sulfonyl isocyanates with dialkyl thioketenes. Phenylisothiocyanate heated with N,C-disubstituted oxaziridines affords 3,5-diimino-l,2,4-dithiazolidines (226, 227). Other miscellaneous syntheses of 1,2,4-dithiazoline derivatives include cyclization of A7-thioacyl hexafluoroacetonimine to 5,5-bis(trifluoromethyl)-... 

Several examples of l,2,4-thiadiazetidin-3-one derivatives have been prepared from the addition of Y triene iminosulfur compounds to sulfonyl isocyanates. The reaction sequence is complex and apparently involves addition, loss of f-butyl isocyanate and subsequent addition to a second molecule of iminosulfur compound. One intermediate has been trapped, and the final product structure was firmly established by X-ray determination to be the 3-one derivative shown in Scheme 136 (78AG(E)677, 80CB2434). 

Thienyl- and 3-thienyl-(tributyl)stannanes react with chlorosulfonyl isocyanate at 20°C to give the corresponding sulfonyl isocyanates by ipso-substitution (Scheme 78). The yields are > 90% (93JOC7022). 

Addition of potassium chloride may be omitted if the chloro-sulfonyl isocyanate is free of sulfur trioxide. Otherwise, traces of sulfur trioxide will give rise to a yellow or brown coloration of the reaction mixture and to formation of small amounts of byproducts which, because of their emulsifying activity, may interfere with further processing. 

Some intramolecular [2+2] cycloadditions of sulfonyl isocyanate-olefins have been studied by Metz et al. [116]. These authors found that the intramolecular reaction depicted in Scheme 36 was calculated to be endergonic at the B3LYP/6-31G and B3LYP(PCM)/6-31G levels, the corresponding free activation energies being in the... 

Scheme 37 Stepwise mechanism computed for the reaction between ethenol (147) and chloro-sulfonyl isocyanate (148)...

All these substances are very sensitive to hydrolysis (89). Functionalization at the nitrogen also takes place in the reaction of the silver salt with CISO2NCO. The sulfonyl isocyanate obtained does not show typical isocyanate reactions. It solvolyzes with H20 or CH3OH without forming intermediates to (CF3SC)4NH. However, with moist air partial hydrolysis leads to the corresponding sulfonamide according to Eq. (8). A number of acyl derivatives were synthesized via Eq. (9). The oxalyl... 

Synthesis of heterocycles, from acyl and sulfonyl isocyanates ... 

The reactions of metal substituted carbodiimides 20 with arenesulfonyl chlorides or arene-sulfonyl isocyanates produce metal substituted N-sulfonylcarbodiimides 21 (R3M=Me3Si, Et3Ge, Bu3Sn X=C1, NCO). ... 

The reaction with aromatic isocyanates such as toluene sulfonyl isocyanate also has been used and the disappearance of this group was followed by IR 119). The content of OH groups in HTPB has been determined by IR after conversion to phtalates 133). 

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