Proceedings of the Scientific Section of the Toilet Goods Association published new progress about 1869-45-0. 1869-45-0 belongs to amides-buliding-blocks, auxiliary class Trifluoromethylated Building Blocks, name is 2,2,2-Trifluoro-N-(2-mercaptoethyl)acetamide, and the molecular formula is C4H6F3NOS, Related Products of amides-buliding-blocks.
Haefele, J. W. published the artcileSynthesis and properties of mercaptans having different degrees of acidity of the sulfhydryl group, Related Products of amides-buliding-blocks, the publication is Proceedings of the Scientific Section of the Toilet Goods Association (1959), 52-9, database is CAplus.
The title compounds were prepared as skin sensitizing materials (Voss, CA 53, 20529e). Mercaptoalkanoic acid amides were made by acylation of amines with the corresponding esters (method 1) or acid chlorides in which the SH group was protected as the Ac derivative (method 2). Another reaction used was the addition of AcSH to olefinic double bonds followed by ammonolysis with NH4OH. Thus, reaction overnight at room temperature of 180 g. Et thioglycolate with 111 g. methylamine in 375 ml. MeOH yielded 123.3 g. N-methylthioglycolamide, b5 91-4°, pK 8.05. Method (1) with increased reaction times and higher temperatures also gave: 73.3% N,N-dimethylthioglycolamide, b5 75-8°, pK 8.10; N-ethylthioglycolamide, 63.5%, b4 92-3°, pK 8.14 (disulfide m. 101°); N-isopropylthioglycolamide, 6%, b4 112° (disulfide m. 94°); N-amylthioglycolamide, 6%, b4 131° (disulfide m. 113°); N-hexylthioglycolamide, 70.5%, b2 134° (disulfide m. 109°); N-decylthioglycolamide, 72.0%, b0.5 163° (disulfide m. 118°); N-hydroxyethylthioglycolamide, 96.1% (81.5% purity), pK 8.10 (disulfide m. 86°); N-methoxyethylthioglycolamide, 51.3%, b2 115°, pK 8.10; N-(diethylaminoethyl)thioglycolamide, 36.6%, b2 122-5°; N,N-bis(2-hydroxyethyl)mercaptoacetamide, 86.0% purity; N-(1,1-dimethylolmethyl)mercaptoacetamide, 86.0% purity; N-(trimethylolmethyl)mercaptoacetamide, 66.0% purity; 2-mercaptopropionamide, 93% purity; thioglycolic hydrazide, 96.5% yield, m. 52-3°, pK 8.05 (disulfide m. 93-4°); 3-mercaptopropionamide, 91% purity; 2-mercaptopropionic hydrazide, 88% purity; 3-mercaptopropionic hydrazide, 96% purity. Acetylthioacetyl chloride (0.2 mole) (from the acid and SOCl2) and 0.2 mole Et glycinate were added simultaneously at a slow rate to a well stirred suspension of 87 g. CaSO4 and 100 g. K2CO3 in 400 ml. ether at 10-15° to yield after 3 hrs. crystalline Et N-(acetylthioacetyl)glycinate, m. 78.5° (ether); this (0.032 mole) with 0.09 mole aqueous NH4OH gave 100% conversion to the free thiol. Tetra-O-acetylglucosamine and acetylthioacetyl chloride in CHCl3 at 0° yielded on precipitation with ligroine 77% N-(acetylthioacetyl)tetra-O-acetylglucosamine, m. 190-1°. Similarly, di-Et N-(acetylthioacetyl)aminomalonate was obtained in 52% yield, m. 91.5° (ether). Mercaptosuccinimide, pK 6.65, was prepared by addition of thiolacetic acid to maleimide in the presence of benzoyl peroxide to give an initial product, m. 91°, hydrolyzed with HCl in MeOH. At 100° in an autoclave, 113 g. morpholine and 78 g. ethylene sulfide gave after 16 hrs. 77.9% N-mercaptoethylmorpholine, b0.9 72-3°, n20D 1.5045. Addition of 68.5 g. ethylene sulfide to 81 g. pyrrolidine in 400 ml. dry dioxane followed by stirring and refluxing 6 hrs. yielded 111 g. N-mercaptoethylpyrrolidine, b22 81°, n20D 1.5004, on distillation of the mixture In the same way were obtained: N-mercaptoethylpiperidine, b18 88°, n20D 1.5011; N-mercaptoethylpyrrolidone (no data); 3-aza-6-oxaheptanethiol, b3 57°, n20D 1.4770; 3-aza-5-(diethylamino)pentanethiol, b0.3 53°, n20D 1.4793. N-(S-Acetylthioethyl)pyrrolidinium chloride was prepared in 81.6% yield by reaction of N-mercaptoethylpyrrolidine with AcCl in benzene and precipitation with hexane, m. 152°. The free base, b0.2 65°, n20D 1.5011, with excess MeI in ether at room temperature gave after 8 days 85% N-(S-acetylthioethyl)-N-methylpyrrolidinium iodide, m. 159-60° (EtOH). N-Mercaptoethyl-N-methylpyrrolidinium iodide, m. 66-7°, 44.8% yield, pK 7.7, resulted on hydrolysis with MeOH-HCl 6 days at room temperature An analogous route yielded: 92.2% N-(S-acetylthioethyl)morpholinium chloride, m. 204°; N-(S-acetylthioethyl)morpholine, 59.5%, b1.5 87°, n20D 1.5050; N-(S-acetylthioethyl)-N-methylmorpholinium iodide, 85.5%, m. 136-9°; N-mercaptoethyl-N-methylmorpholinium iodide, 11.4%, m. 140-3°, pK 7.52. N-Mercaptoethyltrifluoroacetamide, 9.1% yield, b1.2 57-61°, pK 7.28, was obtained by reaction of NaOMe from 2 g. Na in 50 ml. MeOH with 10.5 g. mercaptoethylamine-HCl and 28 ml. Et trifluoroacetate in a sealed tube at 100° 16 hrs. Mercaptoethylurea was prepared from mercaptoethylamine and 2 moles KOCN with concentrated HCl to give β-ureidoethyl thiocarbamate, ionization constant 0.8 × 10-9. S-Acetylthioethyl Me sulfone was prepared by refluxing 61 g. Me vinyl sulfone with 48 g. thiolacetic acid and 1 crystal benzoyl peroxide 20 hrs., extracting with 400 ml. EtOH, and distilling the extract to yield 35 g. reddish brown oil, b0.3 124-38°, crystallized from EtOH to give 16 g. yellow solid, m. 59-60°. Hydrolysis with MeOH-HCl 5 days at room temperature gave 85.9% mercaptoethyl Me sulfone, pale yellow oil, b0.1 105-7°, n20D 1.5240, d20 1.3208, pK 7.92; disulfide m. 152°. Further prepared were hydroxyethyl thioglycolate, b20-30 86-91°, dimethoxyethyl thiomalate, b0.5 130-4°, and N-(S-acetylthioethyl)pyrrolidone, m. 37°.
Proceedings of the Scientific Section of the Toilet Goods Association published new progress about 1869-45-0. 1869-45-0 belongs to amides-buliding-blocks, auxiliary class Trifluoromethylated Building Blocks, name is 2,2,2-Trifluoro-N-(2-mercaptoethyl)acetamide, and the molecular formula is C4H6F3NOS, Related Products of amides-buliding-blocks.
Referemce:
https://en.wikipedia.org/wiki/Amide,
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