Sulfonyl guanidines

In the first step, amines react with 3-(methylsulfanyl)-l,4,2-benzodithiazines to give the corresponding 3-amino compounds (see Section 1.4.6.1.3.1), which may be ring opened by further treatment with a second molecule of amine to afford 2-[(2-sulfanylphenyl)sulfonyl]guanidines... 

Starting from an intermediate l,4,2-benzodithiazin-3-amine, reaction with a different amine yields unsymmctrically substituted 2-[(2-sulfanylphenyl)sulfonyl]guanidines 3.53... 

This sequence is equally applicable to keto esters. Thus, condensation of guanidine with ethyl acetoacetate gives the pyrimidone, 134. Elaboration as above gives the pyrimidine, IJ5 acylation with the sulfonyl chloride (88) followed by hydrolysis yields sulfamerazine (107). Reaction of guanidine with beta dicarbonyl compounds gives the pyrimidine directly. Condensation of the base with acetonyl acetone affords the starting amine for sulfadimidine (108). ... 

For purification, the product is recrystallized from 15 times the amount of a 9 1 mixture of acetone and water. The resulting N -[p-amino benzene sulfonyl]-N -(4,5-dimethyl-oxa-zolyl-(2)] guanidine is obtained as colorless crystals having a MP of 233 to 236°C. 

Zhong HM, Greco MN, MaryanofF BE. Solid-phase synthesis of arginine-containing peptides by guanidine attachment to a sulfonyl linker. J Org Chem 1997 62 9326-9330. 

Thiadiazole 5,5-dioxides (274) have been prepared by the cyclization of A(-halomethyl-sulfonyl amidines and guanidines (273) (Equation (41)) <84CHEC-I(6)463>. 

The guanidine moiety was incorporated by dimethyl (2,2,5,7,8-pentamethylchromane-6-sulfonyl N-alkylated amino) dithiocarbonate[264] (Pmc-dithiocarbonate) 91 in two steps. One methylsulfanyl group was replaced by the primary amino group of Bzl-Norn-OBzl in the presence of excess DIPEA and the isothiourea obtained was reacted with silver nitrate under basic conditions to yield the intermediate sulfonylcarbodiimide which reacts immediately with ammonia to yield the guanidine Bzl-Narg(Pmc)-OBzl 91. 

Lam (4) determined that the presence of either 3-amino- or 3-hydroxyl-benzisoxazol-5-yl in pyrazole derivatives such l-(3,-aminobenzisoxazol-5 -yl)-3-methyl-5-[(2 -amino-sulfonyl-[l, l ]-biphen-4-yl)aminocarbonyl]pyrazole, (III), mimicked the factor Xa-inhibiting properties of guanidine. 

Sulfonyl resins (23) have been developed to prepare indoles via a palladium-catalyzed cyclization. Cleavage was carried out with TBAF with excellent yields and purities (85-100%) [78]. Likewise, a library of bivalent ligands (including guanidine, pyridinium and carboxylic and sulfonic acids constituents) for a protein receptor was prepared on nitrobenzenesulfonamide resin 24. Cleavage was achieved with sodium sulfide [79]. 

It may be prepared by eondensing /7-amino benzene sulfonyl ehloride with guanidine and hydrolysing the resultant in the presenee of sodium hydroxide. 

In fact, under homogenous reaction conditions it was found that the SET mechanism prevailed, affording phenylsulfonyl-derivative 108 as the major product. Similar reactivity patterns were observed in guanidine analogues, with sulfonylation of the 2-NH2 group occurring as the most common side product. 

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