Synthesis from thiocyanic acid

Synthesis from Thiocyanic Add (Isoperthiocyanic and Perthiocyanic Acids)... 

The dipotassium sail of 3,5-dimercapto-l,2,4-thiadiazole ( perthiocyanic acid ) (36) is most conveniently prepared by refluxing a solution of (31) in methanol with sulphur. The salt is readily chlorinated to the stable bis(sulphenylchloride) (37). The observations supplement and further clarify previous work on the synthesis of 1,2,4-thiadiazoles from thiocyanic acid (see Volume 1, p. 448 and ref. 15). 

OZTs from keto sugars. An original approach for the synthesis of OZTs from carbohydrate-based a-hydroxyketones was recently published by Silva et al.4Sa who investigated the reactivity of carbohydrate-based a-hydroxyketone in the presence of thiocyanic acid. 

The synthesis of diaryl-thiazolotriazepines 62 from the reaction of l,2,4-triazepine-3-thiones 63 (1.8 mmol) with 2-haloketones 64 (6.25 mmol) in ethanol under reflux for 2h was described <1999T5909> with the goal of creating new immunomodulating agents (Scheme 5). The starting triazepines were prepared by the addition of thiocyanic acid 65 to the chalcones 66 according to an already known method, followed by reaction of the intermediate 67 with hydrazine. 

Historically, the first example of l,4-(oxa/thia)-2-azole rings was described by Musante, in the late 1930s, who first correctly suggested the 5-imino-2-phenyl 1,4,2-oxathiazole structure 1 to the product obtained from the reaction of ammonium thiocyanate and benzhydroximoyl chloride <1938G331>. Also, the preparation and some properties of dioxazolones 2 described by Beck should be mentioned <1951CB688>, and also the synthesis of the first nonconjugated dioxazole derivative 3, from hydroxamic acid and benzophenone diethylacetal, described by Exner <1956CLY779>. 

Aryl sulfones have been prepared from sulfinic acid salts, aryl iodides and Formation of thiocyanates from unactivated aryl halides has been accomplished with charcoal supported copper(l) thiocyanate. " The copper catalyzed reaction of Na02SMe and aryl iodides give the aryl methyl sulfone. " A similar synthesis of diaryl sulfones has been reported using a palladium catalyst. " ... 

Synthesis.—What appears to be an excellent method for the preparation of amides from carboxylic acids involves treatment of the latter with an amine, Bu"3P, and o-nitrophenyl thiocyanate in THF at 20 °C for 7 h. N,N-Dimethylphosphoramidic dichloride is an alternative to this. °... 

SYNTHESIS To an ice cold and well stirred solution of 15 g vanillin and 20 g sodium thiocyanate in 150 mL acetic acid there was added, dropwise over the course of 15 min, a solution of 16 g elemental bromine in 40 mL acetic acid. This was followed by the addition of 30 mL of 5% HC1 and 300 mL EtOH, and stirring was continued for an additional 30 min. The mixture was heated to its boiling point, and filtered while hot. The mother liquor was diluted with an equal volume of H20, which initiated the crystallization of crude 5-form yl-7-methoxy-2-oxo-l,3-benzoxathiole as a flocculant yellow solid. On filtration and airdrying, this weighed 12.5 g. After recrystallization from EtOH, the product was white and had a mp of 164 °C sharp. 

Another unnatural amino acids synthesis uses an azide reaction (cf. Scheme 2.6), whereas another vancomycin component was derived from the thiocyanate 8 (Scheme 2.11).21-27 28... 

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). 

Scheme 1 One-pot synthesis of lmldazo[l,5-b][l,2,4]triazoles 8 from of a,a-dlsubstltuted a-halo carbonyl compounds 1 with potassium thiocyanate in acetic acid and monosubstituted hydrazines 3.

The earliest method of this type, developed by Marckwald, employed the reaction of a-aminocarbonyl compounds (or their acetals) with cyanates, thiocyanates or isothiocyanates to give 3//-imidazoline-2-thiones. These compounds can be converted readily into imidazoles by oxidation or dehydrogenation. The major limitations of this synthetic procedure are the difficulty of synthesis of a wide variety of the a-aminocarbonyl compounds, and the limited range of 2-substituents which are introduced. The reduction of a-amino acids with aluminum amalgam provides one source of starting materials. The method has been applied to the preparation of 4,5-trimethyleneimidazole (83) from 2-bromocyclopentanone (70AHC(12)103), and to the synthesis of pilocarpine (84 Scheme 47) (80AHC(27)24l). If esters of a-amino acids react with cyanates or thiocyanates, the products are hydantoins and 2-thiohydantoins, respectively. 

The inability of C-terminal proline to be derivatized to a thiohydantoin has been a major impediment to the development of a routine method for the C-terminal sequence analysis of proteins and peptides. Since the method was first described in 1926 (2), the derivatization of C-terminal proline has been problematic. While over the years a few investigators have reported the derivatization of proline, either with the free amino acid or on a peptide, to a thiohydantoin (6-8), others have been unable to obtain any experimental evidence for the formation of a thiohydantoin derivative of proline (9-12). Recently, utilizing a procedure similar to that described by Kubo et al. (6), Inglis et al. (13) have described the successful synthesis of thiohydantoin proline from N-acetylproline. This was done by the one-step reaction of acetic anhydride, acetic acid, trifluoroacetic acid, and ammonium thiocyanate with N-acetyl proline. We have reproduced this synthesis and further developed it to a large scale synthesis of TH-Proline. 

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