Pseudothiohydantoin

Submitted by C. F. H. Allen and J. A. VanAllan. Checked by H. R. Snyder and Frank X. Werber. 

In a 1-1. flask surmounted by a reflux condenser, 76 g. (1 mole) of thiourea, m.p. 174-176°, is dissolved in 500 ml. of 95% ethanol by refluxing for 10-15 minutes. Then 125 g. (108 ml., 1.02 moles) of ethyl chloroacctatc is added slowly (15-20 minutes) through the 

The crude hydrochloride is dissolved in 1200 ml. of hot, freshly boiled water (Note 2) in a 2-1. beaker, a boiling solution of 121 g. of sodium acetate trihydrate in 150 ml. of water is added, and the mixture is heated to boiling (Note 3). The resulting clear solution is stored in the ice chest overnight. The crystalline pseudo-thiohydantoin is filtered and dried to constant weight at 60°. The product weighs 92-95 g. (79-82%). A reproducible decomposition point of 255-258° can be determined with the aid of a melting-point bar (Note 4). 

The yield of the crude hydrochloride, dried to constant weight, is about 126 g. the decomposition range is 210-255°. 

The water is boiled before use to expel dissolved oxygen, the presence of which in the solution may cause the final product to have a yellow color. 

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Thus with ethyl a-chloroacetate (105), R = H, X=C1, Robba and Moreau (530) obtained the 2-amino-4-hydroxythiazole (106), R = H, known as pseudothiohydantoine. 

Protoporphyrin-IX, N-methyl-, 4, 396 Protoporphyrins, 4, 382 photooxygenation, 4, 402 Prototropic tautomerism polyheteroatom six-membered rings, 3, 1055 Prozapine properties, 7, 545 Pschorr reaction carbolines from, 4, 523 dibenzazepines from, 7, 533 dibenzothiophenes from, 4, 107 phenanthridines from, 2, 433 Pseudilin, pentabromo-synthesis, 1, 449 Pseudoazulene synthesis, 4, 526 Pseudobases in synthesis reviews, 1, 62 Pseudocyanines, 2, 331 Pseudothiohydantoin synthesis, 6, 296 Pseudouracil structure, 3, 68 Pseudoyangonin IR spectra, 3, 596 Pseudoyohimbine synthesis, 2, 271 Psicofuranine biological activity, 5, 603 as pharmaceutical, 1, 153, 160... 

Reaction of thiourea with 2-haloacetamides and 2-haloacetates to give pseudothiouronium salts and pseudothiohydantoins [85],... 

Imidazolidin-4-one-2-thiones (21 R = H) are commonly known as thiohydantoins and the isomeric 2-iminothiazolidin-4-ones (22 R = H) have been frequently referred to as pseudothiohydantoins. In earlier... 

The ligand pseudothiohydantoin (110) forms trans-NiL4X2 (Cl, Br, I, C104) and also a cis-NiL4Br2 which probably contains the ligand bonding via the carbonyl oxygen.527 The structures of the octahedral perovskite Sr2[NiW]Oe, and the monoclinic Sr2-[NiTe]Og have been discussed.528... 

Pseudothiohydantoin has been obtained from thiourea and ethyl chloroacetate 1 and from thiourea and chloroacetic2-3 or dichloroacetic acids.4... 

The a-halo acids and their esters also react with thiourea to give 2-amino-4-hydroxythiazoles. Pseudothiohydantoin (237) is thus obtained by condensation of ethyl a -chloroacetate with thiourea and in the course of the reaction it is possible to isolate the acyclic intermediate (236 Scheme 169). Similarly 2,4-diaminothiazole hydrochloride is readily prepared by the reaction of thiourea with chloroacetonitrile in warm alcoholic solution (Scheme 170). 

The simplest synthesis of pseudothiohydantoins (8) is by condensation of thiourea (6) with substituted a-chloroacetates (7)3 5 [Eq. (1)]. Synthons6 of 7, epoxyacids,7 a-chloroacetic anhydrides,8 and dialkyl acetylenedi-carboxylate,9 have been successfully substituted for 7. Symmetrical diaryl-thioureas (9), conveniently synthesized from the corresponding arylamine and carbon disulfide, react with a-haloacetic acid derivatives to give a single thiazolidinone 108,10,11 [Eq. (2)]. 

Pseudothiohydantoine, as acyclic intermediate, in reaction of o-halogeno acids or esters with thiourea, 232. See also 2-Amino-4-hydroxythiazole Pyridazines (4,7-dioxo-4,5,6,7-tetrahydro-thiazolo[4,5d]), preparation of, 206 Pyridine, electronic structure, 36, 39, 46 ultraviolet absorption, 47 thiazolylation of, 373 2-(4-Pyridyl)-4-carboxyethylthiazoie, from thioisonicotinamide and ethyl bromopyruvate, 198... 

Methyl.N (cx3er 3)- thyl-3(oder N )-phenyl-pseudothiohydantoin 27, 250. 

Chloroacetyl groups can be removed from amino functions by use of thiourea in ethanol. The products are the amine HCI which is usually soluble in the reaction medium and pseudothiohydantoin which precipitates. 

With other alicyclic heteroring compounds With pseudothiohydantoin ... 

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