Isocyanates as intermediates

The methodology did not work for secondary amines, thus suggesting the formation of an isocyanate as intermediate (Scheme 27, MX2 = Pdl2, [OX] = (1/2) O2]. However, by reacting a primary amine in the presence of a secondary nucleophilic amine, a general and selective synthesis of trisubstituted ureas has been achieved, through trapping of the isocyanate intermediate by the secondary amine (Eq. 52) [274,275]. 

Isocyanates, as intermediates in Hofmann rearrangement, 812—813 Isoelectric point, 1058—1059 Isoelectronic, 47—48 Isolated diene, 372, 391 L-Isoleucine, 1054, 1059... 

Since then, this protective group has mainly been used in the preparation of sugar-derived isothiocyanates and isocyanates as intermediates in the preparation of thioureas [35-39], ureas [39] or pseudo-nucleosides [40]. 

Carbamates are also formed by one-stage, two-step processes involving isocyanates as intermediates and precursors. Thus, carbamates are prepared under modified Hofmann rearrangement conditions, using NBS/NaOMe as the reagent [443], by Curtius rearrangement of the acyl azide if the reaction is carried out in alcohol, by the reaction of amides with lead tetraacetate [444], or by the Lossen rearrangement, if the carbamates are not sensitive to the presence of base. 

The crucial role of isocyanates as intermediates in this approach has been confirmed by a detailed mechanistic study, which demonstrated that carbamates are by-products that cannot be converted into ureas [221]. 

Aliphatic Isocyanates. Aflphatic diisocyanates have traditionally commanded a premium price because the aflphatic amine precursors ate mote expensive than aromatic diamines. They ate most commonly used in appHcafions which support the added cost or where the long-term performance of aromatic isocyanates is unacceptable. Monofuncfional aflphatic isocyanates, such as methyl and -butyl isocyanate, ate used as intermediates in the production of carbamate-based and urea-based insecticides and fungicides (see Fungicides, agricultural Insectcontroltechnology). 

The insecticide carbaryl can be produced by several routes, some of which do not use methyl isocyanate, or which generate only small quantities of this toxic material as an in-process intermediate (Kletz, 1991b). One company has developed a proprietary process for manufacture of carbamate insecticides which generates methyl isocyanate as an in-situ intermediate. Total methyl isocyanate inventory in the process is no more than 10 kilograms (Kharbanda and Stallworthy, 1988 Manzer, 1994). 

The Preparation and Reactions of Fluoromethyleiies Fluorinated Isocyanates and Their Denvatives as Intermediates for Biologically Active Stibsianccs (Ccr) Radical Reactions of Polyfliioroaromatic Compounds (Russ )... 

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). 

The yV-bromoamide, its anion as well as the isocyanate have been identified as intermediates thus supporting the reaction mechanism as formulated above. 

The addition products of hydrazoic acid and isocyanates have been used as intermediates in the synthesis of monophosphazenes ... 

A few additional points have also been raised by specific surface-science work concerning the catalytic reduction of NO. For instance, it has been widely recognized that the reaction is sensitive to the structure of the catalytic surface. It was determined that rough surfaces such as (110), or even (100), planes enhance NO dissociation over flatter (111) surfaces, and also favor N2 desorption instead of N20 production. On the other hand, NO dissociation leads to poisoning by the resulting atomic species, hence the faster reaction rates seen with medium-size vs. larger particles on model rhodium supported catalyst (the opposite appears to be true on palladium). Also, at least in the case of palladium, the formation of an isocyanate (-NCO) intermediate was identified... 

The hydroxamate anion 566 is invoked as intermediate in the formation of urea 568 from the iV-tosylated /3-lactam 564 by a Lossen rearrangement in the presence of a secondary amine 565 (equation 252). Apparently, attack of amine in an S/v2 fashion at the C(4) carbon of the /3-lactam 564 opened the ring to form hydroxamate anion 566, which then initiated a facile Lossen rearrangement to isocyanate 567 trapped with another molecule of base to give 568. 

Bhopal, the site of the largest chemical accident in the past 50 years, wasn t an explosion but rather an uncontrolled reaction. The plant in Bhopal, India, owned jointly by Union Carbide and the Indian government, was producing methyl isocyanate as an intermediate for a pesticide. Water was admitted into a storage tank containing this chemical, which caused it to hydrolyze and produce CO, HCN, and unreacted MIC, which spread downwind into a crowded slum nearby and caused many deaths and casualties. The desired reaction to synthesize MIC was... 

Isocyanates and isothiocyanates are highly reactive heterocumulenes, and are usually only prepared on solid phase as intermediates for the synthesis of ureas, carbamates, thioureas, etc., using methods similar to those used in solution (Table 14.2). 

Trifluoromethyl isocyanide traps the bis(trifluoromethyI)nitroxyl radical at the terminal carbon atom with the formation of an intermediate radical that decomposes spontaneously to give trifluoromethyl isocyanate as the end product (Table 14).238... 

Fluorinated Isocyanates and Their Derivatives as Intermediates for Biologically Active Substances ... 

Specialty Isocyanates. Specialty isocyanates are organic isocyanates having the isocyanate function attached to a carbonyl group or to elements other than carbon. /t-Toluenesulfonyl isocyanate is used as a drying agent for organic solvents. Arenesulfonyl diisocyanates, such as m-phenylenedisulfonyl diisocyanate, are used as monomers for base-soluble polymers. Arenesulfonyl monoisocyanates are used as intermediates for pharmaceuticals and herbicides. 

In 1882 Hofmann discovered that when amides are treated with bromine in basic solution, they are converted to amines with one carbon less than the starting amide.180 He also isolated the N-bromo amine (114) and the isocyanate (115) as intermediates on the reaction path. The mechanism in Equation 6.56 accounts for the products and the intermediates. This reaction (or the analogous rearrangement of the N-chloro amine) is now known as the Hofmann rearrangement or, because of its synthetic usefulness in eliminating a carbon atom, the Hofmann degradation. 

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