Aminothiols acidity

Isoamyl nitrite/trichloroacetic acid 3,4-Dihydro-3,l92-benzothiadiazin-4-ones from o-aminothiolic acids... 

Potassium hydroxide o-Aminothiolic acids from 3,l-benzoxazine-2,4-diones s. 27, 293 KOH c... 

Other Radioprotective Chemicals. The bis-methylthio- and methylthioamino-derivatives of 1-methylquinolinium iodide and l-methylpyridinium-2-dithioacetic acid provide reasonable protection to mice at much lower doses than the aminothiols, which suggests a different mechanism of action (139). One of these compounds, the 2-(methylthio)-2-piperidino derivative of the l-methyl-2-vinyl quinolinium iodide (VQ), interacts with supercoUed plasmic DNA primarily by intercalation. Minor substitutions on the aromatic quinolinium ring system markedly influence this interaction. Like WR-1065, VQ is positively charged at physiological pH, and the DNA-binding affinities of VQ and WR-1065 appear to be similar. 

Several Pd11 complexes with thiolate or thioether derivative ligands have been studied to be applied in the hydroxycarbonylation reaction.394 Aminothiolate complexes of palladium with PPh3 catalyze the conversion of styrene to 2-phenylpropionic acid in high yield and excellent regioselectivity.644 Under mild conditions and in the presence of a catalytic amount of an S, TV-chelated palladium or//zo-amino-arenethiolate complex, styrene reacts with CO and oxalic acid or water to selectively give 2-phenylpropanic aid in high yield.645... 

The unexpected 1,5-benzothiazepine derivatives 135, with an exocyclic substituted double bond at the 4-position, were obtained in moderate yields (e.g. 135, R = 4-Me, 51%) on reaction of 134 with the aminothiol 136 in acetic acid. The structure of the products was confirmed by detailed ID and 2D NMR experiments <06H(68)1319>. 

The successful application of sulfanyl amines in the diastereoselective and enantioselective synthesis of as-3,4-disubstituted /3-sultams has been reported (Scheme 56). The protocol is based on the oxidation of the 1,2-aminothiols 178 with hydrogen peroxide and ammonium heptamolybdate. Chlorination of the resulting /3-aminosulfonic acids was achieved using phosgene. The /3-aminosulfonyl chlorides 179 obtained were cyclized under basic conditions and without epimerization to yield the t -3,4-disubstituted /3-sultams 180 (>96% de, ee) (Table 13) <2005S1807>. 

Thus we designed and synthesized a bicyclic pyridoxamine derivative carrying an oriented catalytic side arm (16) [11], Rates for conversion of the ketimine Schiff base into the aldimine, formed with 26 (below) and a-ketovaleric acid, indolepyruvic acid, or pyruvic acid, were enhanced 20-30 times relative to those carried out in the presence of the corresponding pyridoxamine derivatives without the catalytic side arm. With a-ketovaleric acid, 16 underwent transamination to afford D-norvaline with 90% ee. The formation of tryptophan and alanine from indolepyruvic acid and pyruvic acid, respectively, showed a similar preference. A control compound (17), with a propylthio group at the same stereochemical position as the aminothiol side arm in 16, produced a 1.5 1 excess of L-norvaline, in contrast to the large preference for D-amino acids with 16. Therefore, extremely preferential protonation seems to take place on the si face when the catalytic side arm is present as in 16. 

Pyrimido[4,5-6][l, 4]thiazine can be obtained by a versatile and convenient method reported by Sako, Maki et al. <9iJCS(Pl)2675> treatment of 5-hydroxyuracil (253 X = 0) and 5-hydroxy-isocytosin (253 X = NH) with TV-bromosuccinimide in ethanol followed by the thermal condensation with (i- and y-aminothiols such as 2-aminothiophenol, cysteamine, L-cysteine, and d,l-homocysteine resulted in the formation of the pyrimido[4,5-6][l,4]thiazines (256). This new method for the construction of pyrimido[4,5-6][l, 4]thiazine ring systems was shown to involve the condensation of 5,6-diethoxy-5-hydroxy-5,6-dihydropyrimidin-4(3//)-one intermediates (255) with / -and y-aminothiols which is accelerated in the presence of an acid catalyst (Scheme 42). 

Pyrimido[4,5-6][l,4]thiazines (262) have been prepared by cyclocondensation of the aminothiols (260) with methyl trifluoropyruvate (261) in benzene (89KGS1492), or with 4-substituted 3-halo-2,4-dioxobutyric acid esters (263) at pH 2-5 in DMF to give 6-carbethoxy-7-acyl derivatives of 5H-pyrimido[4,5-6][l,4]thiazines (264) (Equations (38) and (39)). 

One of the most valuable methods for the preparation of A2-thiazolines is of this class. The reaction of 2-haloalkylamines (334) with thioamides, metal thiocyanates or carbon disulfide give 2-alkyl- or -aryl- (335), 2-amino- (336), and 2-mercapto- (337) A2-thiazolines, respectively (Scheme 218) (17CB804). A method derived from the last procedure leads to a convenient synthesis of 2-phenyl-A2-thiazolines (340) under very mild conditions and consists of the condensation between a-aminothiols (338) and thiobenzoylmercaptoacetic acid (339 Scheme 219) (74TL1863) (this method could be better classified under Type E, Section 4.19.3.2.5). 

Thiazolidines undergo hydrolysis to aldehyde and aminothiol under acidic or basic aqueous conditions. The reaction involves C—S bond breaking and proceeds by the formation of an iminium thiolate zwitterion intermediate 520. The hydrolysis of thiazolidines to aldehydes is conveniently carried out under neutral conditions with the assistance of metal ions such as Hg(II) or Cu(II), e.g., <1997TL2459>. 

Isonicotinic thiamide (270)127 is reduced as other thiamides319 the primary reduction product, the grem-aminothiol, R-CH(SH)NH2, is fairly stable in cold acidic solution, but decomposes on evaporation of the solvent to hydrogen sulfide and the pyridine-4-carbaldehyde. 

Fukuyama [5] obtained the thioester 35 from the reaction of the thiocarboxylic acid anion 34 with the / -lactone compound 17. After acidic deprotection of the Boc group, the thiazoline ring is successfully closed in benzene under Dean-Stark conditions (35 —> 33) in yields between 60 and 80 %. Ehrler [6] and Pattenden [7] choose a more classical way. They close the thiazoline ring by condensation of the aminothiol hydrochloride 5 x HCl with a nitrile. The yields are generally modest (45 and 55 %) except in one case [6]. Installation of the necessary nitrile function hinders its repetitive use, as this procedure causes a considerable loss of material. Heathcock [8] and Ehrler [6 choose the thiol-amide 37 as a key compound. Titanium tetra-... 

Reaction of 5-bromo-6-chloroisocytosine 115 (Scheme 41) with 2-amino-ethanethiol derivatives has been extensively studied by Maki and coworkers [62,63] aimed at the synthesis of folic acid analogues. Treatment of 115 with amino-thiol 116 (R = R = H) in ethanol at reflux temperature in the presence of phosphate buffer at pH 7 provided bicyclic product 121 (R = R = H) in 50% yield. An analogous reaction of aminothiols 116 (R = CH2OH, R = H) and 116 (R = H, R = CH2OH) provided products in 37 and 67% yield, respectively. The mechanism of the reaction is indicated in the scheme. 

Complex aminothiol 123 in reaction with 122 under similar conditions afforded the thio-analogue 124 (X = S) of tetrahydrofolic acid 125 (X = NH) in 45% yield (Scheme 42). 

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