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Org. Synth. 1939, 19, 10
DOI: 10.15227/orgsyn.019.0010
2-AMINO-4-METHYLTHIAZOLE
[Thiazole, 2-amino-4-methyl-]
Submitted by J. R. Byers and J. B. Dickey.
Checked by Louis F. Fieser and Byron Riegel.
1. Procedure
Seventy-six grams (1 mole) of thiourea is suspended in 200 cc. of water (Note 1) in a 500-cc. flask equipped with a reflux condenser, dropping funnel, and mechanical stirrer. The stirrer is started, and 92.5 g. (80 cc., 1 mole) of chloroacetone (Note 2) is run in during thirty minutes. As the reaction proceeds the thiourea dissolves and the temperature rises. The yellow solution is refluxed for two hours and cooled, and, while the mixture is stirred continuously but not so rapidly as to produce a troublesome emulsion, 200 g. of solid sodium hydroxide is added with cooling. The upper, oily layer is separated in a separatory funnel and the aqueous layer is extracted three times with ether, using a total of 300 cc. (Note 3). The dark red oil is combined with the ethereal extract, and the solution is dried over 30 g. of solid sodium hydroxide and filtered by gravity to remove small amounts of tar. The ether is removed by distillation from a steam bath, and the oil is distilled at reduced pressure. After a very small fore-run, 2-amino-4-methylthiazole is collected at 117–120°/8 mm., or 130–133°/18 mm. The yield of material melting at 44–45° is 80–85.5 g. (70–75 per cent of the theoretical amount).
2. Notes
1. The reaction may be conducted without this diluent, but it is then likely to become violent.
2. Commercial chloroacetone was distilled and the fraction boiling at 116–122° taken; nearly all of this boiled at 118–120°.
3. If a precipitate is produced and causes an emulsion, add ice and water until it dissolves.
3. Discussion
The method given is essentially that of Traumann.1 2-Amino-4-methylthiazole has been prepared also from chloroacetone and ammonium thiocyanate;2 from chloroacetone and ammonium thiocyanate in ammonia water;3 by the action of ammonium thiocyanate on thiocyanoacetone;3 by saponifying and decarboxylating the cyclic ester from ethyl γ-bromoacetoacetate and thiourea;4 and from thiocyanoacetone and ammonia in absolute ether.5

References and Notes
  1. Traumann, Ann. 249, 37 (1888).
  2. Hantzsch and Traumann, Ber. 21, 938 (1888); Hantzsch and Weber, ibid. 20, 3118 (1887).
  3. Tscherniac and Norton, ibid. 16, 345 (1883); Tcherniac, J. Chem. Soc. 115, 1071 (1919).
  4. Steude, Ann. 261, 33 (1891).
  5. Hantzsch, Ber. 61, 1785 (1928).

Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)

ammonia (7664-41-7)

ether (60-29-7)

ammonium thiocyanate (1762-95-4)

sodium hydroxide (1310-73-2)

2-Amino-4-methylthiazole,
Thiazole, 2-amino-4-methyl- (1603-91-4)

thiourea (62-56-6)

chloroacetone (78-95-5)

thiocyanoacetone

ethyl γ-bromoacetoacetate