Addition of isocyanates

The rate of addition of isocyanates to enamines increases with decreasing basicity of the isocyanate nitrogen and with increasing basicity of the enamine nitrogen 112). 

The addition of isocyanates (isoelectronic to CO) to group 14 carbene analogs was investigated in order to see if the resulting molecules w ould have an allene-like framework. In the first study, Wcidenbruch et attempted to synthesize... 

Scheme 7.52 Addition of isocyanates to resin-bound amines.

Other microwave-assisted SPOS processes reported in the literature are summarized in Scheme 12.8. The addition of isocyanates to amines bound to Wang resin, for example, was studied both under conventional conditions at room temperature and under the action of microwave irradiation in open vessels by use of a monomode instrument. By monitoring the progress of the addition by on-bead FTIR it was demonstrated that the microwave procedure proceeded significantly faster than the reaction at room temperature (12 compared with 210 min) [38], The temperature during the microwave irradiation experiment was not determined, however, so it is unclear if any nonthermal microwave effects were responsible for the observed rate-enhancements (Scheme 12.8a) [38]. 

The addition of isocyanates to hydroxy compoimds is inhibited by acid compounds (e.g., hydrogen chloride orp-toluenesulfonic acid) on the other hand, it can be accelerated by basic compounds (e.g., tertiary amines like triethylamine, N,hl-dimethylbenzylamine, and especially l,4-diazabicyclo[2.2.2]octane) and by certain metal salts or organometallic compounds (e.g., dibutyltin dilaurate, bismuth nitrate). These catalysts are often effective in amounts of much less than 1 wt%. 

Methyl-5-phenyl-pyrazol-l-yl)-benzoic Acid (27). A mixture of 4-hydrazino-benzoic acid hydrochloride (113 mg, 0.6 mmol) and morpholine-based resin (3) in MeOH (2 ml) was treated with 1-phenyl-butane-1,3-dione (81.5 mg, 0.5 mmol) and shaken for 2.5 h. The MeOH was allowed to evaporate under a stream of N2. DCM (4 ml) was then added to the reaction mixture followed by the addition of isocyanate resin (15) (350 mg). The resulting reaction mixture was shaken for 16 h at which time additional amounts of isocyanate resin (15) (120 mg) were added. The mixture was shaken for 4 h followed by filtration. The filtered resin was washed with DCM (2 x 1.5 ml). Upon concentration of the organic filtrate, clean product was obtained. MS 278.11 (M + 1). 

One of the most facile methods for construction of the (i-lactam skeleton would be [2 + 2] cyclo additions of isocyanates to alkenes. However, the [2 + 2] cycloadditions of alkyl or aryl isocyanides with either 2,3-dihydrofuran or vinyl ethers often fails under normal conditions. High pressure can surmount this difficulty in certain cases. For instance, alkyl isocyanates 125 underwent [2 + 2] cycloadditions with such cyclic vinyl ethers as 126 to produce the P-lactams 127 (Scheme 34) [80]. 

Addition of isocyanates and isothiocyanates, followed by hydrolysis, yields amides, thioamides,274-277 or ureides of j8-ketoacids 82 and 83 are examples of typical intermediates in this reaction. 

In addition to a series of previously well-known reactions of 2-amino-l,3,4-oxadiazoles such as the formation of SchifFs bases or phthalamido derivatives,48-69,81,93 it has been possible to convert 2-amino-5-phenyl-1,3,4-oxadiazole by addition of isocyanate via the corresponding urea into (5-phenyl-l,3,4-oxadiazol-2-yl)diazetidine-diones (45).128... 

Carbodiimides also play a role as building blocks of numerous N-heterocycles. Examples are the cycloaddition reactions of carbodiimides. In the formation of [2-1-2] cycloadducts N-methyl-N -t-butylcarbodiimide is used as a marker to determine the mode of addition of isocyanates or isothiocyanates to carbodiimides. In these reactions addition across the C=N or the C=0 bond of the isocyanate or across the C=N or the C==S bond of the isothiocyanate can occur. Addition to the N-methyl-N -t-butylcarbodiimide always proceeds across the N-methyl double bond. Also, theretroreaction of the [2-1-2] cycloaddition reaction of carbodiimides can afford a different set of heterocumulenes. ... 

The Addition of Isocyanates to Isocyanates (Formation of Carbodiimides) Alkylimino-de-oxo-bisubstitution... 

The addition of isocyanates to glycals, which has been studied thoroughly in connection with new methods of synthesizing lactams [256], usually affords a mixture of [2+2] and [4+2] cycloadducts. These primary reaction products are rather unstable and slowly rearrange to unsaturated amides, which can often be isolated directly from reaction mixtures [257,258]. In the case of simple dihydropyran derivatives 168, unsaturated A-substituted C-2 formamides 170 are the only isolable products (O Scheme 57) [259,260]. 

Regarding the importance of these compounds in various fields of biochemistry, many remarkable reactions have been outlined for the formation of other valuable derivatives. The synthesis of imidazolines begins with the addition of isocyanic acid or thiocyanic acid, as described by Huber and coworkers and Garcia Gonzalez and coworkers. Thiocyanic acid is especially well suited for a direct and easy characterization of the Amadori compounds. A reaction time of 2-3 hours results in a 60-70% yield. 

Tertiary aliphatic isocyanates can be made by addition of isocyanic acid (a toxic material) to olefins (2.17). Cytec (formerly American Cyanamid) makes a diisocyanate this way.58 The reaction can be controlled to produce the monoadduct which can be used as a monomer. Tertiary isocyanates of this type react at lower rates than primary ones in addition reactions. The isocyanic acid can be produced by the pyrolysis of cyanuric acid which, in turn, can be prepared from the urea (reaction 2.18). 

Organylsilylurea derivatives are obtainable via addition of isocyanates to organylam-inosilanes. Thus, N,N-bis(TMS)-aniline (439) with an excess of phenylisocyanate (440) yields l,3-bis(TMS)-1,3-diphenyl urea (441) (equation 204)224. N-organylsilylthiourea... 

Regioselective C-electrophilic addition of isocyanates and isothiocyanates to 2-sub-stituted 1/f-perimidines 601 were carried out by refluxing in anhydrous acetonitrile for a long time (15-163 h) to afford 602 in 66 94% yields. When the addition was carried out under solvent-free conditions using either MWI or an oil bath, the yields were increased to 99% and the times were reduced to 10 25 min (Scheme 118) (96BSF587). 

Polyfunctional isocyanates can be formed in many ways. Commercially, the most important way is through reactions of phosgene with amines or amine salts. Other reactions, however, like that of carbon monoxide with nitro compounds, are now also becoming important. Addition of isocyanic acid to olefins is also gaining prominence. 

This vinyl ether is monomeric in character and is used as a chemical intermediate or os o crosslinking ogent. Addition of isocyanic acid produces secondary diisocyonates. Divinyl ethers hydrolyze to the glycol and acetaldehyde. Chlorine or bromine odd to the double bonds. Reaction with an alcohol in the presence of water produces a diacetal. Polymerization of divinyl ether of diethylene glycol with acidic catolysts produce crasslinked gels. Unsoturoted polyesters, crosslinked with styrene, hove been made noncorrosive to metols through use of divinyl ethers to reduce hydroxyl ond acid numbeis. 

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