Phenylisocyanate

Urethanes. The reaction with phenylisocyanate should be used for crystalline derivative formation (see below), and not as a general reaction for alcohols. 

Some alcohols react readily with phenylisocyanate at room temperature, and others require heating, preferably in petroleum. Phenylisocyanate is poisonous and should not be heated outside a fume-cupboard except under a condenser. 

Example. Add a solution of 0 5 ml. of benzyl alcohol in 5 ml. of petroleum (b.p. 100-120 ) to a similar solution of 0 5 ml. of phenylisocyanate, and boil the mixture gently under reflux for 20 minutes. Filter hot if necessary from any insoluble diphenylurea, and cool. Filter off the crystalline urethane, and recrystallise from the petroleum colourless crystals, m.p. 76 . 

Chemical Designations - Synonyms Carwinate 125 M Diphenylmethane-4,4 -diisocyanate Hylene M50 MDI Methylenebis(4-phenylisocyanate) Multrathane M Nacconate 300 Vilrathane 4300 Chemical Formula (p-OCNC HOjCHj. 

The reaction of isocyanates with enamines disubstituted at the -carbon gives -amino- -lactams (107,108). Thus the enamine (16) reacted exothermally with phenylisocyanate to give (33) dimethyl-l-phenyl-4-dimethylamino-2-acetidinone (157), which was converted by acid hydrolysis to 2-formyl-2-methyl propionanilide (158). 

The addition of phenylisocyanate (427) to enamines was soon found to lead to double acylation products. In the case of the cyclohexanone derived enamine, the first proposal (428) of a second acylation on nitrogen was... 

The addition of phenylisocyanate to aldehyde-derived enamines resulted in the formation of aminobutyrolactams (438,439). As aminal derivatives these produets can be hydrolyzed to the linear aldehyde amides and thus furnish a route to derivatives of the synthetically valuable malonaldehyde-acid system. With this class of reactions, a second acylation on nitrogen becomes possible and the six-membered cyclization products have been reported (440). Closely related to the reactions of enamines with isocyanates is the condensation of cyclohexanone with urea in base (441). 

One of the extensively investigated applications of enamines to heterocyclic syntheses is based on the bifunctional character of enamine acylation products. Thus the vinylogous ureas and thiorueas obtained from enamines and phenylisocyanate and phenylisothiocyanate (-433) have been converted to aminopyrazoles and thiouracils with hydrazine (566) and phenylisocyanate (567). 

Other derivatives of 3-aminopropanol and 3-halogenopropylamine can also be used to form 2-iminotetrahydro-l,3-oxazine deriva-tives. In some instances phenylisocyanate can be used as a cyclizing agent. ... 

Hydrogenolysis, without ring reduction, of the carbon-oxygen bond in phenols cannot be depended on, but by conversion of the phenol to a better leaving group, such as is formed by interaction of the phenol with 2-chlorobenzoxazole, l-phenyl-5-chlorotetrazole, phenylisocyanate,... 

Dibenz[c,e]azepine 6-oxide, a cyclic nitrone (see Section 3.2.1.5.1.), yields crystalline 1,3-dipolar cycloadducts with phenylisocyanate (adduct yield 98 % mp 190-191 C) and with N-phenylmaleimide (adduct yield 86% mp 235-236°C).6... 

Thus unsubstituted (R=H) and substituted (R = alkyl) non-stabilized diyiides 1 react with phenylisocyanate and dicyclohexylcarbodiimide (R NCX), leading to the formation of new monoylide type intermediates. These last ones react in situ with carbonyl compounds through a Wittig type reaction leading respectively to a,)8-unsaturated amides 2 and amidines 3, with a high E stereoselectivity, the double bond being di- or tri-substituted [48,49]. By a similar reactional pathway, diyiides also react with carbonic acid derivatives, with the synthesis as final products of -a,/l-unsaturated esters 4 and acids 5 [50]. 

Analogously, when the above sequence was followed with pyrrole, ring closure of 141 did occur (when n = 2 or 3) but the cycloadduct 142 underwent rearomatization to an oxime which added to phenylisocyanate providing carbamate 143 in moderate yield [40]. 

If it is heated alone at 160°, ammonia comes off rapidly, the aniline and phenylisocyanate may be detected by their odor but they combine in large part to form 5ym.-diphenyliu ea which crystallizes out from the hot liquid, and cyanic acid may be detected by means of silver nitrate in the water with which the apparatus is washed out after the experiment. When an aqueous solution of phenylurea is distilled, aniline may be detected in the distillate and 5ym.-diphenylurea crystallizes from the boiling liquid. By heating urea with the amine or with its hydrochloride at 160°, or by refluxing urea in aqueous solution with the amine or its hydrochloride, we have prepared sym.-6i-o- and />-tolyl, di-a- andjS-naphthyl, dimethyl, di-w-butyl, di-w- and i5 -amyl and dibenzylureas in satisfactory yield. 

When 5ym.-ethylphenylurea is heated alone at 160°, ethylamine escapes and the phenylisocyanate and aniline combine to form 5ym.-diphenylurea. The imea dearrangement then provides the true explanation of the apparently metathetical reaction in which the ethyl groups of 5ym.-diethylurea are successively replaced by phenyl. ... 

Reactions of the hydrido(hydroxo) complex 2 with several substrates were examined (Scheme 6-14) [6]. The reactions are fairly complicated and several different types of reachons are observed depending on the substrate. Methyl acrylate and small Lewis bases such as CO, P(OMe)3, BuNC coordinate to the five-coordinated complex 2 affording the corresponding six-coordinate complexes. In reactions with the unsaturated bonds in dimethylacetylenedicarboxylate, carbon dioxide, phenylisocyanate indications for the addition across the O-H bond but not across the Os-OH bond were obtained. In reactions with olefins such as methyl vinyl ketone or allyl alcohol, elimination of a water molecule was observed to afford a hydrido metalla-cyclic compound or a hydrido (ethyl) complex. No OH insertion product was obtained. 

It is well established that primary amino-functional groups, particularly aliphatic ones, react instantaneously with isocyanates to form ureas at ambient temperature. Indeed this was observed when 6-aminoethylferrocene (3) and freshly distilled phenylisocyanate were shaken vigorously. A yellow precipitate separated out immediately. Elemental analysis and an IR spectrum of the product indicate this compound to have the structure 6. ... 

Combinatorial solid-phase synthetic methodologies have been used extensively in drug development [8]. A new solid-phase synthesis of 2-imidazolidones has been discovered by Goff, based on a domino aminoacylation/Michael addition reaction [9]. Thus, when immobilized amine 10-26 (HMPB-BHA resin) was treated with phenylisocyanate in the presence of triethylamine, a smooth formation of 2-imida-zolidone took place. Acid-catalyzed removal from solid phase provided 10-27 in good yield (Scheme 10.6). 

An aza-Wittig reaction-cycloaddition reaction sequence was utilized for the synthesis of pyridotriazines 94. Treatment of iminophosphorane 92 with phenylisocyanate leads to the formation of the corresponding carbodiimide intermediate, which with another molecule of isocyanate affords 94 in [4+2] heterocycloaddition reactions (Equation 13) <1997T16061>. 

PTAD reacts with 625 at elevated temperature to give only low yields of bicyclic compound 626. The low yield is presumably caused by decomposition of PTAD to carbon monoxide, nitrogen, and phenylisocyanate (Scheme 101) <1999JHC627>. 

In another variation on a type C synthesis which yields 5-substituted-3-oxo-l,2,4-thiadiazolines, the reaction of arylthioamides with phenylisocyanate affords the arenethiocarboxamide 89, which can then be transformed into product 90 by direct oxidation with bromine (Equation 26) <1996CHEC-II(4)307>. 

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