Isothiocyanates, addition

Addition of amines to isocyanates or isothiocyanates Addition of amines to CO2 or CS2... 

Azole approach. 2-Aminooxazoline forms a cycloadduct with ethoxycarbonyl isothiocyanate. The orientation of the substituents in the adduct shows that the reaction is initiated by isothiocyanate addition to the exocyclic nitrogen (264) (71CB3039). 

Control of pH is especially important in plant enzyme isolation. As a generalization, low pH is desirable. Phenolic compounds, which are ubiquitous in plants, ionize at high pH, and this makes them subject to spontaneous air-oxidation (and subsequent covalent-addition reactions). Ionized phenolics will not form H-bonded complexes either with proteins or with adsorbent polymers. The former might be desirable, but the latter is not. A principal target of covalent addition reactions with proteins is the un-ionized -NH2 group. This applies to 1, 4-addition by quinones md sesquiterpene lactones and to the isothiocyanate addition reaction. Low pH converts amino groups to the unreactive ionized form. Obviously the general factors of protein chemistry also apply, such as possible denaturation or isoelectric precipitation. 

Alky]-5-imino-3-methy -A2-l,2,4-thiadiazoIines react exotherm ally at 0°C with dibenzoy] or dimethoxy carbonylacetylenes in tetrahydrofuran to give the 2-alkylaminothiazoles in high yields (1564). The cycio addition reaction of 2-pyridyl isothiocyanates with 1-azirines results in the formation of 2-pyridylaminothiazoles (1565). 

Adducts from various quaternary salts have been isolated, in reactions with aldehydes, a-ketoaldehydes, dialkylacylphosphonates and dialkyl-phosphonates, isocyanates, isothiocyanates, and so forth (Scheme 15) (36). The ylid (11) resulting from removal of a Cj proton from 3.4-dimethyl-S-p-hydroxyethylthiazolium iodide by NEtj in DMF gives with phenylisothiocyanate the stable dipolar adduct (12) that has been identified by its NMR spectrum and reactional product, such as acid addition and thiazolidine obtention via NaBH4 reduction (Scheme 16) (35). It must be mentioned that the adduct issued from di-p-tolylcarbodiimide is separated in its halohydrogenated form. An alkaline treatment occasions an easy ring expansion into a 1,4-thiazine derivative (Scheme 17) (35). 

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). 

In a manner analogous to classic nitrile iinines, the additions of trifluoro-methylacetonitrile phenylimine occur regiospecifically with activated terminal alkenes but less selectively with alkynes [39], The nitnle imine reacts with both dimethyl fumarate and dimethyl maleate m moderate yields to give exclusively the trans product, presumably via epimenzation of the labile H at position 4 [40] (equation 42) The nitrile imine exhibits exo selectivities in its reactions with norbornene and norbornadiene, which are similar to those seen for the nitrile oxide [37], and even greater reactivity with enolates than that of the nitnle oxide [38, 41], Reactions of trifluoroacetomtrile phenyl imine with isocyanates, isothiocyanates, and carbodiimides are also reported [42]... 

The addition of isocyanides and azide to aldehyde-derived enamines has led to tetrazoles (533,536). On the other hand the vinylogous amide of acetoacetic ester and related compounds reacted with aldehydes, isocyanides and acids to give a-acylaminoamides (534). Iminopyrrolidones and imino-thiopyrrolidones were obtained from the addition of cyclohexylisocyanide and isocyanates or isothiocyanates to enamines (535). An interesting method for the formation of organophosphorus compounds is found in the reactions of imonium salts with dialkylphosphites (536). 

The 1,2,3,4-thiatriazoles are unstable. They decompose on heating— in some cases even at room temperature—and in many cases they melt with detonation. Accordingly the Ng-group has not been stabilized much by ring closure. The compounds behave in this respect similarly to azides and this fact doubtlessly delayed the recognition of their true nature. On heating with a solvent the thermal decomposition of 5-aryl-1,2,3,4-thiatriazoles proceeds according to Eq. (4). By the photochemical decomposition small amounts of the isothiocyanate, RNCS, are formed in addition to the nitrile. ... 

Nucleophilic addition of the peptide terminai amino group to p nenyi isothiocyanate (PITC) gives an /V-phenylthiourea derivative. 

Related to this process is the hydrolysis of isocyanates or isothiocyanates" where addition of water to the carbon-nitrogen double bond would give an N-substituted carbamic acid (3). Such compounds are unstable and break down to carbon dioxide (or COS in the case of isothiocyanates) and the amine ... 

Ammonia and primary and secondary amines can be added to isocyanates to give substituted ureas. Isothiocyanates give thioureas. This is an excellent method for the preparation of ureas and thioureas, and these compounds are often used as derivatives for primary and secondary amines. Isocyanic acid (HNCO) also gives the reaction usually its salts (e.g., NaNCO) are used. Wohler s famous synthesis of urea involved the addition of ammonia to a salt of this acid. "... 

Salts of dithiocarbamic acid can be prepared by the addition of primary or secondary amines to carbon disulfide. This reaction is similar to 16-9. Hydrogen sulfide can be eliminated from the product, directly or indirectly, to give isothiocyanates (RNCS). Isothiocyanates can be obtained directly by the reaction of primary amines and CS2 in pyridine in the presence of DCC. ° In the presence of diphenyl phosphite and pyridine, primary amines add to CO2 and to CS2 to give, respectively, symmetrically substituted ureas and thioureas ... 

Other thietane derivatives have been obtained by isomerization of nitrogen-containing heterocycles. The reaction of an acyl isothiocyanate (RCONCS) with diphenyldiazomethane gave 20 and this isomerized in solution to the tetraphenyl-3-thietanone 21 <96BSB253>. Additionally, the isoxazolidine 22 was converted into 23 by the action of trimethylsilyl iodide and zinc iodide <96H1211>. 

Natural products have been noted for their potential health benefits from time immemorial and are the basis of Ayurveda, an ancient Indian medical practice (Bushkin and Bushkin, 2002). However, the potential benefits of several natural products reside in one or two active ingredients. For example green tea stands for polyphenols, soy for soy estrogens, broccoli for isothiocyanates and grape seed for polyphenols. The beauty of rice bran is that there are more than 100 antioxidants, several categories of bioactive phytonutrients, such as IP6, polyphenols, phytosterols, tocotrienols, y-oryzanol, B vitamins, minerals and trace minerals in addition to fat, protein, fiber, polysaccharides and other nutrients. These phytonutrients and antioxidants of rice bran are believed to act at the cellular level, and their synergestic function is responsible for the positive health benefits. 

Reaction of dimsyl anion with isothiocyanates gives a-thioamidosulphoxides 478 in 12-59% yield, whereas with isocyanates it affords a mixture of a-amidosulphoxides 479 and methylsulphinylmalonoamides 480, the products of a double addition " (equation 289). 

Note that carbon monoxide inserts into the Zr-H bond of 1 (2 equiv.) to afford an T -formaldehydo-type complex [(Cp2ZrCl)]2(g-CH20) [200-202]. Iminoacyl zir-conocene complexes are formed after addition of 1 to isonitriles [203]. Carbon dioxide [183, 202] is reduced to formaldehyde with 1 (2 equiv.). C02-like molecules such as isocyanates RNCO [204], isothiocyanates RNCS [205], and carbodiimides RNCNR [204] are readily converted to the corresponding bidentate form-amido ligands. 

The formation of compounds 2-503 proceeds via the addition of a hydrazide 2-500 onto the central carbon of an isothiocyanate 2-499. Subsequent cyclization by attack of the hydrazide nitrogen in the formed 2-501 onto the nitrile moiety gives intermediate 2-502. A further attack of the newly formed amidine nitrogen onto the carbonyl group followed by extrusion of water affords the triazoloquinolines 2-503. 

It has been shown by Zanardi, Nanni and coworkers that, instead of isocyanides, isothiocyanates can be used in the radical process [90]. Treatment of the mixture of the diazonium tetrafluoroborates 3-217 and the isothiocyanates 3-218 with pyridine or a mixture of 18-crown-6 and potassium acetate in ethyl acetate, furnished the benzothienoquinoline derivatives 3-219. In addition, in some cases the rearranged products 3-220 were furnished in low to reasonable yields (Scheme 3.57). 

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