Isocyanates ring closures with

The dimethylsulfonium ylide (568) added readily to aroyl isocyanates to give the intermediate addition product (569). This on heating underwent ring closure with loss of dimethyl sulfide to form the 4-hydroxyoxazole (570) (73T1983). This normal C-acylation of the sulfonium ylide also leads to thiazoles with thiobenzoyl isocyanate in this case the initial acylation product was not isolated, the thiazole being obtained directly. 

Conjugated heterocumulenes generated in situ by an aza-Wittig reaction are also capable of electrocyclic-ring closure with a subsequent 1,3-H shift. This principle, applied for the first time by Saito et al. on butadiene iminophosphorane 51 (Scheme 28) by treatment with isocyanate and isothiocya-... 

The synthesis of cyanurates 215 started with condensation of the corresponding amines with an excess of nitrobiuret 214 (method A, Scheme 33). Subsequent ring closure with diethyl carbonate and sodium ethoxide gave compound 215 in good yields. Similar results could be obtained by the reaction of the same amines with A -chlorocarbonyl isocyanate (method B, Scheme 33) <2002CEJ2288>. 

Ring closures with isocyanates 3,4-Dihydro-4-hydroxy-2H-l,3-benzoxazin-2-ones from o-hydroxyaldehydes and isocyanates... 

A related ring closure with formation of 3-phenyl isocarbostyril 226 is observed in the photolysis of /3-styril isocyanate 225. ... 

In the reaction of ketoglutaric acid esters with aryl isocyanates ring closure of the initiallly formed insertion products 231 occurs to produce the heterocycle 232 . ... 

Hydroxy-THISs add to the C-C bond of diphenylcyclopropenethione (181. Inner salts without substituents in 5-posnion react similarly with diphenylcyclopropenone (Scheme 10) (4, 18). Pwolysis of the stable adducts (9) leads to rupture of the R-C-CY bond. Subsequent ring closure yields 10. When Y = O. 10 eliminates COS. producing 2-pyridone. When Y = S. 10 is isolated together with its isocyanate extrusion product, a thiopyran-2-thione (18). 

An excess of phosgene is used during the initial reaction of amine and phosgene to retard the formation of substituted ureas. Ureas are undesirable because they serve as a source for secondary product formation which adversely affects isocyanate stabiUty and performance. By-products, such as biurets (23) and triurets (24), are formed via the reaction of the labile hydrogens of the urea with excess isocyanate. Isocyanurates (25, R = phenyl, toluyl) may subsequendy be formed from the urea oligomers via ring closure. 

In many pyrimidine ring syntheses, it is possible or even desirable to isolate an intermediate ripe for ring-closure by the formation of just one bond. For example, ethyl 3-aminocrotonate (502) reacts with methyl isocyanate to give the ureido ester (503) which may be isolated and subsequently converted into 3,6-dimethyluracil (504) by the completion of one bond. However, viewed pragmatically, the whole synthesis involves the formation of two bonds and therefore is so classified. On such criteria, only two pyrimidine/quinazoline syntheses involve the formation of only one bond. 

Propargyl alcohol (332) and (328) react readily with isocyanates in the presence of a basic catalyst to give 4-methylene-2-oxazolidinones (334) and 4-methylene-2-imidazolinones (336), respectively (63JOC991). In the absence of sodium methoxide the intermediate methanes (333) and ureas (335) were obtained and on treatment with sodium methoxide underwent ring closure. Moderate to excellent yields were obtained. 

Treatment of benzodiazepine 4 with methyl isocyanate gives (lie urea 4, which in the presence of sodium ethoxide undergoes ring closure to 4-amino-3-methyl-l//-pyrimido[4,5-h][l,5]ben-zodiazepin-2(3/T)-one (15).293... 

A useful method to synthesize ten and fourteen-membered ring imides 346 involved an initial condensation of macrocyclic -ketoestes 343 with alkyl or aryl isocyanates and carbodiimides, respectively, in the presence of a base [68]. After a nucleophilic attack of the enolate on the isocyanate C, the resultant amide N anion 344 induced a ring closure by addition to the keto group. Then, the intermediately formed four-membered ring 345 underwent a fragmentation... 

We entered this field when we studied the photoisomerization of simply substituted nitrile oxides 138 (R = Cl, Br, CN).188 Matrix irradiation yields the corresponding isocyanates 144. In the case of chloronitrile oxide besides the absorptions of chloroisocyanate189 the bands of chloronitrene190 also appear. It can be assumed that the nitrile oxide-isocyanate rearrangement starts with the ring closure 138 - 140.191192... 

Additionally, uracil 6-iminophosphorane, isocyanate, and o-methyl-e-caprolactim ether join to form the intensely yellow pyrimido[4 5 4,5] pyrimido[6,l-n]azepine (360), as shown in Scheme 130. Upon ring closure, methanol is spontaneously eliminated. Diethyl azodicarboxylate affords with the other components pyrimido[4,5-e][l,2,4]triazoline (361), which is closely related to the alkaloid isofervenuline. The imidazo[5, -/][ ,2,4]tria-zine (362) results in a known Michael-type rearrangement sequence by treatment with diethyl acetylenedicarboxylate (86JOC149, 86JOC2787) in this latter case, the Michael-type addition occurs much faster than the expected three-component reaction [93H(35)1055]. 

Further routes of cyclizations have been studied in parallel in the case of cis- and rra/J5-2-hydroxymethyl-l-cyclohexylamine (106) (880PP73). The preparation of thiourea or urea adducts 107 and 108 with phenyl isothiocyanate or phenyl isocyanate proceeds smoothly. The reaction of 107 with methyl iodide and subsequent alkali treatment, by elimination of methyl mercaptan, resulted in the iminooxazine 109 in high yields. The ring closures of both cis and trans thiourea adducts to 1,3-oxazines proceed with retention. Cyclodesulfuration of the adduct 107 by mercury(II) oxide or N,N -dicyclohexylcarbodiimide resulted in the iminooxazine 109, but the yield was low and the purification of the product was cumbersome. The ring closure of 108 with thionyl chloride led to the iminooxazine 109 in only moderate yield. 

Carbodiimides react with (144) to give triazoline-5-thiones, while with isocyanates the tri-azolinones are formed after ring closure of the initial product by heating in excess SOCI2 (Scheme 28) <89S923>. 

One principal access to 1,2,4-oxadiazoles consists of N—O bond formation by electrocyclic ring closure of nitrenoids N—CR —N—CR =0. For instance, heating acyl isocyanates (159) with trimethylsilyl azide alfords high yields of 1,2,4-oxadiazoles (Scheme 68) <79JCS(P1)185,80JOC5130). Similarly, elimination of HCl from A -chloroamidines (160) (Scheme 69) <84BCJ1I6> and ther-... 

Substituted (l//,3 -quinazol>ne-2,4-diones 774, as well as the 3-unsubstituted parent compound 774 (R = H), are available by treatment of 2-[(trichloroacetyl)amino]benzamides 772 with sodium hydroxide in DMSO. The reaction proceeds via intermediate isocyanate compounds 773 which undergo ring closure to the final products <20050PP560>. 

An interesting one-carbon ring closure is found in the reaction of 94 (prepared from phenylcyanothioformamide and 1,3-diphenylpropenone) with either/)-chlorobenzoyl chloride or phenyl isocyanate to give pyrrolo[3,2- thiazoles 95 and 96, respectively (Scheme 18) <1999PSS(148)117>. However, attempted extension of this reaction sequence to include acetic anhydride did not afford a pyrrolo[3,2-i71thiazole product. In a novel approach, the same workers obtained additional examples of pyrrolo[3,2- thiazoles 99 in excellent yield as the only isolable product by reaction of A-(4-chloro and 4-methylphenyl)cyanothioformamide 97 with arylidene 98 the formation of the product was rationalized via 100-103 as detailed in Scheme 19 <2005PS(180)573>. 

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