Isothiocyanates preparation

Jobbagy, A., and Jobbagy, G.M. (1973) Examination of FITC preparations. I. Measurements of the dye content of fluorescein isothiocyanate preparations./. Immunol. Meth. 2, 159-168. 

Thiophanate (81) is prepared by treating o-phenylenediamine (84) with ethoxycarbonyl isothiocyanate (prepared in situ by heating KNCS with ClCOOEt) [64] (Scheme 10). 

A few drug discovery synthesis routes were used to diversify the thiohydantoin structures. The first route exploited a convergent concept where a three-component Strecker reaction of an amine, a ketone and trimethylsilyl cyanide was used to generate (he cyanoamine analog 24 (Scheme 1). Isothiocyanate prepared from the amine with thiophosgene was added to the cyanoamine to give thiohydantoin -imine 25 which was hydrolyzed to afford the desired thiohydantoins 26. 

Although a good deal of variety in structure is conceivable with bifunctional isothiocyanates, preparative methods are generally routine. An example is the conversion of ClaFCSCl through several steps into ClaFCSNCS. ... 

Preparations of Isothiocyanates.—Preparations from isocyanides have been studied by several groups, showing that aryl isocyanides with elemental... 

Wang CY, Song Q, Xi Z (2004) Reactions of 1,4-dilithiobutadienes with isothiocyanates preparation of iminocyclopentadiene derivatives via cleavage of the C=S double txmd of a RN=C=S molecule. Tetrahedron 60 5207-5214... 

The HSAB pattern may also be reversed by steric effects a Japanese patent describes the preparation of 3-(4-R-thiazolyl-2)thioallophanic acid esters (151) by reaction between 2-amino-4-R-thiazoles (4-R = H or low alkyl) and isothiocyanate formic acid ester (Scheme 96) (309). 

DiaminO 4,4-dimethyl-l,3,5-thiadiazine hydrobromide was isolated as by-product (418). Benzene sulfonates of cyanohydrin prepared from sodium cyanide and an halobenzoaldehyde, when treated with thiourea or its derivatives, afford 2,4-diamino-5-(p-halogenophenyl)-thiazole benzene sulfonates (447). Similarly, cyanoamido thiocarbamates obtained from cyanamide and isothiocyanates yield substituted 2,4-diaminothiazoles (598). 

Substitution of alkaline cyanates by isocyanates allows the preparation of 3-substituted hydantoias, both from amino acids (64) and amino nitriles (65). The related reaction between a-amino acids and phenyl isothiocyanate to yield 5-substituted 3-phenyl-2-thiohydantoiQS has been used for the analytical characterization of amino acids, and is the basis of the Edman method for the sequential degradation of peptides with concomitant identification of the /V-terminal amino acid. 

Immobilization. The fixing property of PEIs has previously been discussed. Another appHcation of this property is enzyme immobilization (419). Enzymes can be bound by reactive compounds, eg, isothiocyanate (420) to the PEI skeleton, or immobilized on soHd supports, eg, cotton by adhesion with the aid of PEIs. In every case, fixing considerably simplifies the performance of enzyme-catalyzed reactions, thus faciHtating preparative work. This technique has been appHed to glutaraldehyde-sensitive enzymes (421), a-glucose transferase (422), and pectin lyase, pectin esterase, and endopolygalacturonase (423). 

AletalHydrides. Metal hydrides can sometimes be used to prepare amines by reduction of various functional groups, but they are seldom the preferred method. Most metal hydrides do not reduce nitro compounds at all (64), although aUphatic nitro compounds can be reduced to amines with lithium aluminum hydride. When aromatic amines are reduced with this reagent, a2o compounds are produced. Nitriles, on the other hand, can be reduced to amines with lithium aluminum hydride or sodium borohydride under certain conditions. Other functional groups which can be reduced to amines using metal hydrides include amides, oximes, isocyanates, isothiocyanates, and a2ides (64). 

This method obviates the need to prepare the intermediate aryl isothiocyanate. 

Thioureas give thioxo analogues of a variety of the above syntheses (52JOC542), although these thioxo products are usually prepared from isothiocyanates (Section 2.15.5.2.1). Examples are known in the pyrido-[2,3-[Pg.225]

Amongst the more unusual reactions, 2,3-thiazolo fused pyrido[3,2-d]pyrimidines have been prepared from 3-aminopicolinic acid and 2-bromothiazoles, whilst a similar derivative resulted with allyl isothiocyanate (221 222) <72IJC602). Similar products are also produced in [3 + 3] reactions of 2-aminothiazoles (Section 2.15.5.7.1). 

Azoles containing a free NH group react comparatively readily with acyl halides. N-Acyl-pyrazoles, -imidazoles, etc. can be prepared by reaction sequences of either type (66) -> (67) or type (70)->(71) or (72). Such reactions have been carried out with benzoyl halides, sulfonyl halides, isocyanates, isothiocyanates and chloroformates. Reactions occur under Schotten-Baumann conditions or in inert solvents. When two isomeric products could result, only the thermodynamically stable one is usually obtained because the acylation reactions are reversible and the products interconvert readily. Thus benzotriazole forms 1-acyl derivatives (99) which preserve the Kekule resonance of the benzene ring and are therefore more stable than the isomeric 2-acyl derivatives. Acylation of pyrazoles also usually gives the more stable isomer as the sole product (66AHCi6)347). The imidazole-catalyzed hydrolysis of esters can be classified as an electrophilic attack on the multiply bonded imidazole nitrogen. 

Several related derivatives have also been utilized in this type of synthesis. Imino-chloromethanesulfenyl chlorides (184), prepared by the controlled addition of chlorine to isothiocyanates, react with amidines (161) to give 1,2,4-thiadiazolines (185) (71T4117). Chlorocarbonylsulfenyl chloride (186), prepared by the hydrolysis of trichloromethanesulfenyl chloride with sulfuric acid, reacted with ureas, thioureas and guanidines to give 1,2,4-thiadiazolidine derivatives (187) <70AG(E)54, 73CB3391). 

Heating or irradiating alkenes in the presence of sulfur gives relatively low yields of thiiranes. For example, a mixture of sulfur and norbornadiene in pyridine-DMF-NHa at 110 °C gave a 19% yield of the monoepisulfide of norbornadiene as compared with a 78% yield by the method of Scheme 120 (79JCS(Pi)228). Often 1,2,3-trithiolanes are formed instead of thiiranes. The sesquiterpene episulfides in the essential oil of hops were prepared conveniently by irradiation of the terpene and sulfur in cyclohexane (Scheme 135) (80JCS(Pl)3li). Phenyl, methyl or allyl isothiocyanate may be used as a source of sulfur atoms instead of elemental sulfur. 

This thiourea, prepared from an amino acid and phenyl isothiocyanate, is cleaved by anhydrous trifluoroacetic acid (an N-COCF3 group is stable), and by oxidation (/72-CIC6H4CO3H, 0°, 1.5 h, 73% yield H2O2/ACOH, 80°, 80 min, 44% yield). ... 

Chlorophenyl isothiocyanate has also been prepared by treating an alcoholic solution of sym-di-/)-chlorophenyl thiourea with iodine/ from ammonium -chloroplienyldithiocarbamate and lead nitrate/ (p. 72), and from the action of thiophosgene with /)-chloroaniline. ... 

This reaction is a general method of preparation for aryl isothiocyanates in yields of 50-75 per cent of the theoretical amount. 

Phenyl isothiocyanate has been prepared from thiocarbanilide by the action of phosphorus pentoxide, hydrochloric acid, iodine, phosphoric acid, acetic anhydride, and nitrous acid. It has also been prepared from ammonium phenyl dithiocarbamate by the action of ethyl chlorocarbonate, copper sulfate lead carbonate, lead nitrate, ferrous sulfate,and zinc sulfate. ... 

The method is generally applicable to the preparation of aryl isothiocyanates. Using this procedure, the submitters have prepared the following isothiocyanates, with the yields and times of refluxing indicated phenyl, 44%, 8 hours o-chlorophenyl, 46, 8 -bromophenyl, 73, 8 j>-biphenylyl, 49, 6 /3-naphthyl, 70, 10 9-phenanthryl, 70, 10 1-pyrenyl, 72, 10. 

Aryl isothiocyanates can be prepared by the action of thio-phosgene on the arylamine (this reaction fails with naphthyl compounds), by fission of a 5ym-diaryIthiourea with acidic reagents (this reaction involves the loss of half the amine used), and by the decomposition of an ammonium aryldithiocar-bamate (low yields are reported for naphthyl and other compounds).The procedure described here is that of Baxter, Cymerman-Craig, Moyle, and White. ... 

The reaction of the enamines of cyclic ketones with alkyl isocyanates, acyl isocyanates, phenyl isothiocyanates, and acyl isothiocyanates has also been reported 112). The products are the corresponding carboxamides. The products from the isothiocyanates have been utilized as intermediates in the preparation of various heterocyclic compounds 113). 

Thiocyanates and selenocyanates can be made by fusing the corresponding cyanide with S or Se. The SCN and SeCN ions are both linear, like OCN . (See p, 779 for TeCN ) Treatment of KSCN with dry KHSO4 produces free isothiocyanic acid HNCS, a white crystalline solid which is stable below 0° but which decomposes rapidly at room temperatures to HCN and a yellow solid H2C2N2S3. Thiocyanic acid, HSCN, (like HOCN) has not been prepared... 

Further investigation on this type of thiazole synthesis in subsequent years led to the preparation of 5-aminothiazoles in which the 2-position was varied through reaction of the aminonitrile with salts and esters of dithioacids, carbon disulfide, carbon oxysulfide, and isothiocyanates. 

Substituted 2-mercapto-4(3i/)quinazolinones were prepared by condensing methyl anthranilate with isothiocyanates (see 7c). 

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