Isocyanates, addition hydrolysis

Diels-Alder addition of 2-chloroacrylonitrile and dienes gives the expected adducts, e.g. (310), which may be converted via azide, isocyanate, and hydrolysis to the ketone (311) in good yield. This constitutes a method for 1,4-addition of the methylenecarbonyl unit (—CHgCO—) to dienes. Among the many 1,3-dipolar additions of olefins recently reported are the intramolecular nitrone-olefin cycloadditionse.g. (312) (313), and the... 

Anilides and a-Naphthalides. The Grignard reagents prepared from alkyl halides react with phenyl isocyanate (CgHjN=C=0) or with a-uaphthy l isocyanate (C,oH, N=C=0) to yield addition products that are converted by hydrolysis into anihdes and a-naphthalides respectively RX + Mg —> RMgX... 

Synthesis from OC-Amino Acids and Related Compounds. Addition of cyanates, isocyanates, and uiea derivatives to a-amino acids yields hydantoin piecuisois. This method is called the Read synthesis (2), and can be considered as the reverse of hydantoin hydrolysis. Thus the reaction of a-amino acids with alkaline cyanates affords hydantoic acids, which cyclize to hydantoins in an acidic medium. 

The chiral bicyclic imidazolidine 74 is deprotonated at the 2 position by s-BuLi and the resulting anion adds to alkyl halides, acid chlorides, chlorofor-mates, phenyl isocyanate, and aldehydes. The use of this compound as a chiral formyl anion equivalent seems to be limited, however, since the diastereoselectiv-ity in the addition to aldehydes is poor and hydrolysis of the products 75 to give aldehydes also produces cyclohexane-1,2-diamine, necessitating isolation of the aldehyde as its 2,4-dinitrophenylhydrazone (96SL1109 98T14255). 

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 ... 

The addition of Grignard reagents to isocyanates gives, after hydrolysis, N-substituted amides. This is a very good reaction and can be used to prepare derivatives of alkyl and aryl halides. The reaction has also been performed with... 

Fig. 11.11. Mechanism postulated for hydrolysis of organic isocyanates involving electrophilic addition of H20 with general base catalysis. The product of hydration is a carbamic acid that spontaneously decomposes to the primary amine with loss of C02 [117].

Fusion of an all cyclic ring onto the piperidine so as to form a perhydroisoquinoline is apparently consistent with analgesic activity. Synthesis of this agent, ciprefadol (68), starts with the Michael addition of the anion from cyclohexanone 56 onto acrylonitrile (57). Saponification of the nitrile to the corresponding acid (58) followed by Curtius rearrangement leads to isocyanate J9. Acid hydrolysis of the isocyanate leads directly to the indoline... 

The acidic nature of the reagent is important the trifluoroacetic acid liberated in the reaction catalyzes hydrolysis of the intermediate isocyanate, and also ensures that the amine which is formed is protonated and cannot react with the isocyanate to give urea by-products. The reaction can be accelerated by addition of pyridine to an observed pH of about 3.5, and is retarded by added acid or trifluoroacetate ion. In the present procedure pyridine was not employed, since the reaction in its absence proceeds with a satisfactory rate. 

Environmental Fate. Extensive information is available on the general reactions of isocyanates that may pertain to the environmental fate of HDI (Chadwiek and Cleveland 1981 Kennedy and Brown 1992). However, investigations of the environmental fate of isocyanates have focused primarily on TDI and MDI (Duff 1983, 1985 Gilbert 1988 Holdren et al. 1984). Only one laboratory study was located in the available literature specifically on the ehemieal reaetions of HDI (i.e., bicarbonate buffer-catalyzed hydrolysis) that may be relevant to the environmental fate of HDI in water (Berode et al. 1991). HDI is expected to react relatively rapidly with hydroxyl radieals in the atmosphere and to be rapidly hydrolyzed in water and moist soils and sediment. The signifieanee of atmospheric hydrolysis has not been evaluated. Additional field and laboratoiy studies are needed to adequately eharacterize the environmental fate of HDI in air, water, soil, and sediment. 

Initially, water can cause the hydrolysis of the anhydride or the isocyanate, Scheme 28 (reaction 1 and 2), although the isocyanate hydrolysis has been reported to occur much more rapidly [99]. The hydrolyzed isocyanate (car-bamic acid) may then react further with another isocyanate to yield a urea derivative, see Scheme 28 (reaction 3). Either hydrolysis product, carbamic acid or diacid, can then react with isocyanate to form a mixed carbamic carboxylic anhydride, see Scheme 28 (reactions 4 and 5, respectively). The mixed anhydride is believed to represent the major reaction intermediate in addition to the seven-mem bered cyclic intermediate, which upon heating lose C02 to form the desired imide. The formation of the urea derivative, Scheme 28 (reaction 3), does not constitute a molecular weight limiting side-reaction, since it too has been reported to react with anhydride to form imide [100], These reactions, as a whole, would explain the reported reactivity of isocyanates with diesters of tetracarboxylic acids and with mixtures of anhydride as well as tetracarboxylic acid and tetracarboxylic acid diesters [101, 102]. In these cases, tertiary amines are also utilized to catalyze the reaction. Based on these reports, the overall reaction schematic of diisocyanates with tetracarboxylic acid derivatives can thus be illustrated in an idealized fashion as shown in Scheme 29. 

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