Isothiocyanates with aromatic rings

N-Substituted amides can be prepared by direct attack of isocyanates on aromatic rings.The R group may be alkyl or aryl, but if the latter, dimers and trimers are also obtained. Isothiocyanates similarly give thioamides. The reaction has been carried out intramolecularly both with aralkyl isothiocyanates and acyl isothiocyanates.In the latter case, the product is easily hydrolyzable to a dicarboxylic acid this is a way of putting a carboxyl group on a ring ortho to one already there (34 is... 

Isothiocyanates react with many nucleophiles, but only the products with amines (thiocarbamoyl derivatives) are stable.16 Although the increased specificity is desirable, the reaction with the amino group changes the charge on the protein, and this may be needed in order to maintain the activity or the conformation, or both. The linkage formed is alkali-labile, and, as with the azo derivatives, the aromatic ring is a liability. 

A series of 2-imidazolidin-2-one substituted benzothiazoles 62 are prepared from O-amidinylhydroxylamines 58 with aryl isothiocyanates 59 in moderate yields <05PJC115>. The reaction pathway has been proposed to proceed via iminocarbonyl sulfenamide 61, which undergoes spontaneous sulfurization of the aromatic ring with loss of 1-aminocyclohexanecarbonitrile to furnish benzothiazole 62. 

Trimerization of nitriles, isocyanates, isothiocyanates, imidates, and carbodiimides all lead to symmetrical 2,4,6-trisubstituted 1,3,5-triazines (see Section 6.12.9.5). The use of lanthanide trifluoromethanesulfonate and ammonia as cocatalysts is claimed as a big improvement. The trisaminal of 2,4,6-triformyl-l,3,5-triazine is also useful for further derivatization to unusual structures (see Section 6.12.7.1). Treatment of a 1 1 pyridine/conc. ammonia solution of an aromatic aldehyde with excess Fremy s salt is another development. Separation of the amide coproduct was claimed to be easy. The synthesis fails with aliphatic aldehydes (see Section 6.12.9.5.4). Aminolysis of 2,4,6-triaryl-1,3,5-oxadiazinium salts gives symmetrical 1,3,5-triazines but the reactions are limited in that electron-withdrawing groups in the aromatic rings lead to instability and difficulty in separation of products (see Section 6.12.10.4). 

Capillary zone electrophoresis with microchip-based SCCE has been used to separate fluorescent dye from degradation products and to separate fluorescein isothiocyanate (FITC) labeled amino acids. Capillary zone electrophoresis (CZE) in fused-silica capillaries has been used to separate the racemic mixtures of (a-hydroxybenzyl)methyltrimethylammonium and (2-hydroxy-l-phenyl)ethyltrimethylammonium with f)-cyclodextrin as the chiral pseudo-stationary phase. L-Phenylalanine and L-phenylalanine-ring-D5 (the hydrogens in the aromatic ring were substituted with deuterium) and another separation of the closely related amino acids phenylalanine and tyrosine have been resolved using CZE with capillary-based SCCE. ... 

Also, four-membered ring cycloadducts resulting from addition across the C=S bond are obtained in the reaction of Ph3P=C=C=S with aromatic isothiocyanates. Likewise, in the reaction of Ph3FM2=C=NR with isothiocyanates the cycloadducts 39 are obtained. ... 

Cyclic thioureas containing six-membered rings condense with aromatic isothiocyanates in the presence of mercury bis(phenylacetylide), in a similar manner to that described previously (see p. 401) for 2-mercaptoimidazoline, to give, eventually, the methiodide (84). Thiazolo[3,2-a]pyrimidine-5,7-diones, on alcoholysis or aminolysis, give the corresponding 2-substituted thiazoles [SO R = C(0)CHsCOsAlk or C(0)CHaC(0)NHAlk]. 3 ... 

An interesting variation of this quinoxaline synthesis is outlined by the synthesis of sydnoquinoxalines shown in Scheme 103. The starting material is phenylsydnone 288 with an iminophosphorane group in an o-position. With isocyanate or isothiocyanate carbodiimide intermediates 289 are formed by an electrophilic aromatic substitution at the sydnone ring (4 position), the 4-(arylamino)sydno[3,4-a]quinoxalines (290) are obtained (91S745). 

In these two syntheses, the a-haloketone supplies two carbon atoms to the thiophene ring. In a different approach, the a-haloketone provides only one of the carbon atoms of the ring, the other three carbon atoms being derived from the nitro-containing reagent. Nitroketeneaminals are first treated with aliphatic or aromatic isothiocyanates to form the adducts 35. Reaction with a-haloketones then leads to the 5-acyl-3-nitrothiophenes 36 (20-50%) (Scheme 8).30,31... 

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