Aminoethanethiols

Reaction of 2-aminoethanethiol hydrochloride with hydroxymethylfurazan 61 in 48% aqueous hydrobromic acid (reflux, 24 h) gave a salt that on treatment with an equimolar amount of 3,4-dimethoxy-l,2,5-thiadiazole 1,1-dioxide and another amine gave compound 62 (84USP4471122) (Scheme 30). 

The N,S-chelate 2-aminoethanethiolate (aet-) forms stable cobalt(III) complexes, including clusters where the S can take on a bridging role. Reaction of [Co(NH3)5C1]2+ with Ni(aet)2 in water for several hours affords the black tetranuclear compound Co4(aet)8, which features act in simple chelate and bridging roles (245).1083 The simple monomeric complex [Co(aet)2(en)]+ has been reported 1084 when heated in water at 50 °C, the trimer Co Co(aet)3 2 is one product, with the central Co surrounded by six bridging S atoms. 

The demonstration of the formation of a hexanuclear zinc complex with the S-donor ligand 2-aminoethanethiolate, containing Zn3S3 and Zn4S4 cyclic units, contributes to the building up of a pattern of polynuclear complex formation based on coordination preferences of the metal ions involved (320) - reaction of Zn2+ with salicylideneamino ligands and pyrazine can give linear tetranuclear complexes (321). Another hexanuclear zinc complex appears in the section on supramolecular chemistry below (Section VII.D). 

Fife et ai, 1975. The reference reaction is attack by 2-aminoethanethiolate anion (pA, 8.3) onp-nitrophenyl N-methyl-N-phenylcarbamate, corrected to pK 8.7... 

The reaction mode depends mainly on the choice of the base and reaction conditions, but route B is usually more common. Thus, tetrahydro-l,4-thiazine derivative 157 the structure of which was proved by X-ray crystal structure analysis (Fig. 7) [22b] was obtained in the reaction of the chloro ester 1-Me with 2-aminoethanethiol (156) using K2CO3 or EtgN as a base in 43 and 20% yield, respectively (Scheme 49) [22b, 26]. In the latter case, the secondary amino group in the primary tetrahydrothiazine product 157 underwent Michael addition to a second molecule of 1-Me to give 2-[r-(spirocyclopropanetetrahydrothiazinyl) cyclopropyl]-2-chloroacetate 158 (14% yield). When KOH in the presence of di-benzo-18-crown-6 was employed, however, the seven-membered heterocycles 155 (42%) and 159 (48%) were obtained upon reaction of 1-Me with 1,3-pro-panedithiol and 2-aminoethanethiol, respectively (Scheme 49) [26]. 

Replacement of the OH groups of the salen ligands with SH produces a potentially tetradentate ligand, BAT-TM [tetramethylbis(aminoethanethiol)]... 

An S-acetylated 2-aminothiol was reacted with 2-chloroacyl chlorides (Equation 85) <1989JPS937>. The reactions of 2-aminoethanethiol with 2,3-butanedione <1998JFA2278>, alkynyl cyanide 279 <1993TL5681>, and cyclic hemiacylal 281 <1992FI(34)2131> are shown in Scheme 59. Mechanisms for the formation of products 277, 278, and 280 were suggested, but not however for the unexpected product from 281. 

Both 2-aminoethanethiol and 2-aminothiophenol can be reacted with the same chloroenamine 282 to give 121 and 122 (Scheme 60) <2005RJ0508>. 

Both 2-aminoethanethiol and 2-aminothiophenol were reacted with epoxyesters to give thiazin-3-ones (Scheme 71) <1999J(P1)149>. 

Published routes to pyrazino[2,3-3][l,4]thiazines, as reviewed in CHEC-II(1996) <1996CHEC-II(7)737>, involved the reaction of a 3-aminopyrazine-2-thiol with a biselectrophile and of a 3-chloropyrazin-2-amine with thioglycolate. In more recent work, the system is formed by condensation of a dichloropyrazine with a 2-aminothiophenol (Equation 182) <2002CPB922>. The same approach, using either 2-aminothiophenol or 2-aminoethanethiol, has been used to form oxadiazole-fused systems (Scheme 100) <1997CHE1352>. In studies toward the synthesis of ER-49890 151, benzannulated pyrazino[2,3-/ ][l,4]thiazines have also been accessed by an indirect sequence (Scheme 101)<2005H(65)403>. 

The condensation of 2-aminoethanethiol with a l,2-bis(electrophile) to give a mixture of perhydro-l,4-thiazino[3, 2-3][l,4]thiazine and 2,2 -bis(thiazolidine) was included in CHEC-II(1996) <1996CHEC-II(7)737>. The direct preparation of this target from glyoxal was not achieved, but this method has been used successfully for the preparation of 166 (Equation 192). 

Reactions of this type provide major routes to both the monocyclic system and to 1,5-benzothiazepines. In some cases the reactions are single-stage processes but in many cases the intermediate produced by the primary formation of the S—C bond can be isolated. Thus 2-aminoethanethiol reacts with a,/3-unsaturated or j3-halogeno ketones to give (408). Similarly reaction with a,/3-unsaturated acids, esters or acid chlorides and with 3-halogenopropionyl halides gives the 5-oxo derivative (409). 2-Aminoethanethiol also reacts with activated 2-chlorobenzophenones to give 1,4-benzothiazepines. 

The superoxo-containing species [(NC)6Co(/u.-02)Co(CN5]5 can be reduced with thiols such as 2-aminoethanethiol or L-cysteine (175), and the reduction reaction is catalyzed by copper(II) ions in aqueous solution. When copper(II) is present, the role of the thiol is to reduce cop-per(II) to copper(I), which then reacts with the superoxo species through an inner-sphere mechanism. Conversely, when the superoxo complex [(H3N)5Co(/x-02)Co(NH3)5]5+ is reduced with thiol (176), the reaction follows an outer-sphere mechanism, as would be expected. Ascorbic acid also reduces both complexes (177), but only the reduction of the cyano-containing complex exhibits copper(II) catalysis. 

Table 40 Some Oxovanadium(IY) Complexes Derived from Salicylaldehyde or Substituted Salicylalde-hyde with 2-Aminoethanethiol (83), 3-Aminothiophenol (84) or 2-Aminothiophenol (86) (on reflux)...

Aminoethanethiol reacts with ot, 3-unsaturated or (3-halo ketones to give (355). Similarly, reaction with a, (3-unsaturated acids, esters or acid chlorides, and with 3-halopropionyl halides, yields 5-oxo derivatives such as (356). Thioglycollic acid (HSCH2C02H) with 3-bromopropylamine gives (357). 

In lieu of preparing and handling large amount of ethylene sulfide, ethyl 2-mercaptoethylcarbonate (XII) has been employed uiib advantage in the mercaptoethylation of primary and secondary amines.8 Introduction of this carbonate into a refluxing solution ol amine in toluene promotes its decomposition to ethylene suJfi.K carbon dioxide and ethanol. The ethylene sulfide react with the amine to give the 2-aminoethanethiol (Eq, 47). 

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