Aryl isothiocyanate

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

Hydrazinopyridazines are easily formylated with formic acid or ethyl formate and acety-lated with acetic anhydride. A-Pyridazinylthiosemicarbazides are obtained from thiocyanates or alkyl- and aryl-isothiocyanates. Hydrazinopyridazines condense with aliphatic and aromatic aldehydes and ketones to give hydrazones. 

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

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 synthesis of 5-aminothiazoles via the reaction of isocyanate derivatives with aminomalononitrile p-toluenesulfonate (AMNT) has been investigated. It was found that AMNT 12 reacted with alkyl and aryl isothiocyanates in l-methyl-2-pyrrolidine (NMP) to furnish 5-amino-2-(alkylamino)-4-cyanothiazoles (13a) and 5-amino-2-(arylamino)-4-cyanothiazoles (13b-c) in 44-81 % yields. " ... 

Treatment of 3-amino-4-oxoquinazolines (9) with cyanamide gave the 2-amino-l,2,4-triazolo [l,5-c]quinazolines 11 as a result of cyclodehydration of the intermediate 3-guanidino-4-oxoquinazolines 10 (68CB2106) (Scheme 9). Similarly, reaction of the 3-amino-4-thioxoquinazoline 12 with alkyl or aryl isothiocyanates yielded the mesoionic l,2,4-triazolo[l,5-cjquinazolines 14 (84S881) (Scheme 10). 

Cycloaddition of 2-nitrosopyridine 48 with nitrile oxides can give either di-A -oxides such as 49 or 3-mono-A -oxides such as 50 (93JHC287). In general, greater electron withdrawing character in the aromatic substituent appears to favor formation of the di-A -oxides. Sulfur ylides such as compound 51 are obtained from aryl isothiocyanates and l-amino-2-methylthiopyridinium iodides (84JCS(P1)1891) nitrogen ylides can be obtained from a similar reaction (86H(24)3363). 

The synthesis of 987 from 985 via 986 has been reported (83S759) by reaction of 985 with aryl isothiocyanates under neutral conditions. The reaction of 4-amino-6-anilino[l,2,4]triazine 988 with methyl iodide and then carbon disulfide gave 989 (90MI3, 90MI9). 

Glutaconaldehyde anion serves as an interesting intermediate for the synthesis of heterocyclic compounds. The parent pyrylium perchlorate has been prepared from glutaconaldehyde and 70% perchloric acid in ether at -55°.° The reaction of glutaconaldehyde anion with alkyl and aryl isothiocyanates and... 

The reaction of 1-amino-1-deoxyketoses, and their N-alkyl and N-aryl derivatives, with alkyl or aryl isothiocyanates (Huber et al, 1960) was studied in more detail, and new 4-(alditol-l-yl)-l-alkyl(aryl)-3-alkyl(aryl)-l,3-dihydro-2H-imidazole-2-thiones were obtained. These compounds were used as starting materials for the synthesis of OL-histidines, DL-histidine-2-thiol, and other imidazole derivatives of biological interest. 

In analogy to the thiohydantoin synthesis, the PEG-bound diamines have also been treated with various alkyl and aryl isothiocyanates and, after applying traceless cyclative cleavage, the desired thioxotetrahydropyrimidinones were obtained in excellent yields. In contrast to the thiohydantoin synthesis, purification of the products was more complicated if the excess of isothiocyanate amounted to more than 2.2 equivalents [85],... 

A)-5,5-Dimethyl-thiazoline-4-carboxylic acid reacted efficiently with alkyl and aryl isothiocyanates to give bicyclic thiohydantoins 418. A similar diastereo- and regioselective cyclization of chiral l,3-thiazolidine-2,4-dicarboxylic acids was also reported (Equation 191) <1996JHC1099, 1998HCA744>. 

Contrasting with the reported formation of fused [l,3,4]thiadiazole rings in the course of the reaction of 3-substituted-4-amino-5-thio-47/-[l,2,4]triazoles 83 with various isothiocyanates (cf. Section 11.07.8.3, Table 3), the reactions with methyl isothiocyanate and with phenylisocyanate afford 3,7-disubstituted-6,7-dihydro-57/-[l,2,4]triazolo[4,3-f] [l,2,4]triazole-6-thiones 110 and -triazole-6-ones 111, respectively (Equation 29) <1986MI607, 1992IJB167>.The same reaction of 4-amino-l-methyl-3,5-bis(methylthio)[l,2,4]triazolium iodide 112 with aryl isothiocyanates yields the mesoionic compounds 113 (Equation 30) <1984TL5427, 1986T2121>. 

Aryl-3-phenacylthio-l,2,4-triazoles 122 react with carbon disulfide and aryl isothiocyanates to give 5-aryl-3//-[l,2,4]triazolo[3,4-f][l,2,4]dithiazole-3-thiones and the 3-arylimino derivatives 123 (Equation 35) <1983ABC1017>. 

Transformations of [l,3,4]thiadiazolylazomethines to thiadiazolo[3,2-tf][l,3,5]triazinones are demonstrated in Scheme 32. The azomethines 161 containing various aryl groups were treated with different aryl isothiocyanates... 

Diethyl malonate was reacted with (het)aryl isothiocyanates in the presence of potassium hydroxide or sodium hydride in dioxane or THF at... 

Dimethyl (arylamino)cyanomethylenemalonates (349) were prepared in 27-52% yields in the reactions of aryl isothiocyanates and potassium cyanide in methanol at room temperature for 45 min, followed by treatment with dimethyl chloromalonate for 3 hr (77S607). 

Alkyl and glycosyl isocyanates and isothiocyanates are produced in good yield under phase-transfer catalytic conditions using either conventional soluble catalysts or polymer-supported catalysts [32, 33]. Acyl isothiocyanates are obtained under similar conditions [34]. A-Aryl phosphoramidates are converted via their reaction with carbon disulphide under basic conditions into the corresponding aryl isothiocyanates, when the reaction is catalysed by tetra-n-butylammonium bromide [35]. 

Substituted 1,2,3-triazolium-l-aminide 1,3-dipoles (382) react with aryl isothiocyanates at both the N=C (path a) and C=S (path b) sites to give mixtures of substituted imidazolo[4,5-fi(][l,2,3]triazoles (383) and new thiazolo[4,5-fi(][l,2,3]-triazoles (384) including tricyclic derivatives with the C(3a) and C(6a) bridgeheads linked via (CH2)4 and phenanthro groups (Scheme 50). The product distribution is controlled by the para-substituent of the aryl isothiocyanate. Theoretical calculations at the 3-210 and 6-3IG levels suggest that linear triple-bonded canonical forms of the aryl isothiocyanate system play a key role in the ambident reactivity of these systems. 

In a variation of this approach the reaction of amidrazone ylides (230) with both alkyl and aryl isothiocyanates yields thiocarbonyl substituted amidrazone ylides (231) which can be thermally cyclized to 5-amino-1,2,4-thiadiazoles (232) with the elimination of trimethylamine (Scheme 50) <81JHC201>. 

Furthermore, a cycloreversion has been observed in the case of the thermally labile azoniaallene salts (61) (Z = O, S). When Z = S, this proceeds within an hour at room temperature to yield the aryl isothiocyanate and the charged cumulene (66) which is isolated as the acyliminium salt (67) <9ICB2537>. When Z = O and R = Ph, cycloreversion occurs at 83°C (refluxing 1,2-dichloroethane) to give the aryl isocyanate and (66), which is further cyclized to the quinazolinium salt (68) (Scheme 4) <89T5825>. 

Aryl isothiocyanates react with alkyl azides to form a mixture of thiatriazolines but the primary products cannot be isolated. 

A second type of synthetic route to meso-ionic l,3,4-thiadiazol-2-imines (247) is based on the acid-catalyzed reaction of N-thioacylhydrazines (232) with aryl isothiocyanates (Ar-NCS). " This reaction yields the s ts (248) as precursors of the meso-ionic heterocycles (247). An interesting variant upon this route involves the reaction between IV-thioacylhydrazines (232) and acyl isothiocyanates (RCO-NCS). This leads to the meso-ionic heterocycles 247, R = COzEt, CONMej, COMe, COCMe, COAr, and SOjPh. The investigation of these compounds by X-ray photoelectron spectroscopy is a good example of the application of this physical method for the examination of meso-ionic compounds. 

A successful method for preparing 1,3-thiazetidines is the cycloaddition of carbodiimides with isocyanates. The cycloadduct 151 was derived by the interaction of carbodiimide 152 and tosyl isothiocyanate . Reaction of 152 with methyl or phenyl isothiocyanate preferentially leads to iminotriazine-thiones. Cycloaddition between aryl isothiocyanates and dicyclohexylcar-bodiimide produced 153. ... 

N-3-Substituted 2-thioxo-4-quinazolinones 859 are formed when alkyl or aryl isothiocyanates are reacted with anthranilic acids or esters 857, <2001JME1710, 2002AP556, 2004JC0584, 2006JME2440>. The intermediate di-substituted thiourea 858 is normally not isolated, but is directly ring-closed in situ to the thioxoquinazolinone product 859. When 3-unsubstituted products are required, benzoyl isocyanate can be used <20008714>. 

---