Isomerization isocyanate

The synthesis of 3- and 7-substituted indoles (184 and 185) by [3,3]-sigmatropic rearrangement of A-hydroxyindole derivatives (181) was reported (equation 54). A-hydroxyindole 181 in the presence of cyanogen bromide (182, R = Br, = N) and base afforded 183 that rearranged to the NCO substituted at position 3 and position 7, leading to two isomeric isocyanates, 184 and 185, respectively. Different behaviour was found when an acetylenic sulfone 182, R =11, R = CTos, was used where the 3-substituted indole 186 was the only rearrangement product identified. 

Retro-ene type [2 r + In + 2a] and [3,3]-sigmatropic shift reactions involving the substituent groups R in heteroatom-substituted cyanates and thiocyanates RX-YCN and the isomeric isocyanates and isothiocyanates of the type RX-NCY (X = CR2, NR, O, or S, Y = O or S) have been investigated computationally (Scheme 3). ... 

Isocyanates are derivatives of isocyanic acid, HN=C=0, ia which alkyl or aryl groups, as weU as a host of other substrates, are direcdy linked to the NCO moiety via the nitrogen atom. StmcturaHy, isocyanates (imides of carbonic acid) are isomeric to cyanates, ROCMSI (nitriles of carbonic acid), and nitrile oxides, RCMSI—>0 (derivatives of carboxyUc acid). 

Olefin isomerization can be catalyzed by a number of catalysts such as molybdenum hexacarbonyl [13939-06-5] Mo(CO)g. This compound has also been found to catalyze the photopolymerization of vinyl monomers, the cyclization of olefins, the epoxidation of alkenes and peroxo species, the conversion of isocyanates to carbodiimides, etc. Rhodium carbonylhydrotris(triphenylphosphine) [17185-29-4] RhH(CO)(P(CgH )2)3, is a multifunctional catalyst which accelerates the isomerization and hydroformylation of alkenes. 

Azoles containing a free NH group react comparatively readily with acyl halides. N-Acyl-pyrazoles, -imidazoles, etc. can be prepared by reaction sequences of either type (66) -> (67) or type (70)->(71) or (72). Such reactions have been carried out with benzoyl halides, sulfonyl halides, isocyanates, isothiocyanates and chloroformates. Reactions occur under Schotten-Baumann conditions or in inert solvents. When two isomeric products could result, only the thermodynamically stable one is usually obtained because the acylation reactions are reversible and the products interconvert readily. Thus benzotriazole forms 1-acyl derivatives (99) which preserve the Kekule resonance of the benzene ring and are therefore more stable than the isomeric 2-acyl derivatives. Acylation of pyrazoles also usually gives the more stable isomer as the sole product (66AHCi6)347). The imidazole-catalyzed hydrolysis of esters can be classified as an electrophilic attack on the multiply bonded imidazole nitrogen. 

The photochemical addition of azirines to the carbonyl group of aldehydes, ketones, and esters is also completely regiospecific (77H(6)143). Besides the formation of the isomeric oxazolines (50) from (39) and ethyl cyanoformate, there is also formed the imidazole (51) from addition to C=N in the expected regioselective manner. Thioesters lead to thiazolines (52), while isocyanates and ketenes produce heterocycles (53). 

The hydroxyl derivative of X-CN is cyanic acid HO-CN it cannot be prepared pure due to rapid decomposition but it is probably present to the extent of about 3% when its tautomer, isocyanic acid (HNCO) is prepared from sodium cyanate and HCI. HNCO rapidly trimerizes to cyanuric acid (Fig. 8.25) from which it can be regenerated by pyrolysis. It is a fairly strong acid (Ka 1.2 x 10 at 0°) freezing at —86.8° and boiling at 23.5°C. Thermolysis of urea is an alternative route to HNCO and (HNCO)3 the reverse reaction, involving the isomerization of ammonium cyanate, is the clas.sic synthesis of urea by F. Wohler (1828) ... 

Substituted azocine systems are much more stable than the parent compound, and 2-methoxy derivatives have been intensively examined. Starting from cyclohexa-1,4-diene (3), a [2 + 2] cycloaddition with chlorosulfonyl isocyanate, followed by removal of the chlorosulfonyl group, leads to the /3-lactam 4, which can be transformed by O-methylation with Meerwein s salt into the corresponding imidate. Monobromination with A-bromosuccinimide and subsequent treatment with base results in a methoxyazabicyclo[4.2.0]octatriene derivative, which spontaneously isomerizes to 2-methoxyazocine (5).13,14... 

With isocyanates R"N=C=0 as unsymmetrical heterocumulenes the reactivity to yield bis(insertion)products is markedly higher and there are many more possibilities (2) for isomerism. In fact, we find now that the product selection is more varied than reported in a previous article [3], and that e. g. the use of 1 R,R = Me, and phenyl- or isopropylisocyanate results in mixtures of isomers, even at low temperatures. Sterically more discriminating derivatives of 1 with R = Me, R = rm-Bu and R = wo-Pr, R = H yield one major stable isomer with PhN=C=0 which could be identified as the (cis O, N ) form by NMR spectroscopy. 

Reaction of 2-cyanomethylpyridine with iV-(l-aryl-l-chloro-2,2,2-trifluoroethyl)-iV -(4-methylphenyl)carbodiimides, and with (1,1,2,2,2-pentachloro- and l,l-dichloro-2,2,2-trifluoroethyl)isocyanates or A-methoxycarbonyl-l,2,2,2-tetrachloro-, — l-chloro-2,2-trifluoroacetaldehyde imines afforded 3-aryl-4-cyano-l-(4-methylphenyl)imino-3-trifluoromethyl-2,3-dihydro-17/-pyrido[l,2-f]pyrimidines and 4-cyano-3-trichloro-, 4-cyano-3-trifluoro-17/-pyrido[l,2-4pyrimidin-l-ones, respectively <2004CHE47>. Refluxing 2-cyanomethylpyridine and iV-(l-aryl-l-chloro-2,2,2-trifluoroethyl)isocyanates in benzene furnished l-aryl-4-cyano-l-trifluoromethyl-l,2-dihydro-3//-pyrido[l,2-4pyrimidin-3-ones. However, when the solution of the isocyanate was added dropwise to the solution of 2-cyanomethylpyridine, and the reaction mixture was then treated with NEt at room temperature, the isomeric 3-aryl-4-cyano-3-trifluoromethyl-2,3-dihydro-l//-pyr-ido[l,2-dpyrimidin-l-ones were obtained. Reaction of l-(acetyl- and benzoylmethylene)-6,7-dimethoxy-l,2,3,4-tetra-hydroisoquinolines with PhCONCS yielded 1-acetyl-, 1 -benzoyl-9,10-dime thoxy-3-pheny 1-6,7-dihydro-2//-pyrimido[6,l- ]isoquinoline-2-thiones <2003SL2369>. 

These routes are dimerization to furoxans 2 proceeding at ambient and lower temperatures for all nitrile oxides excluding those, in which the fulmido group is sterically shielded, isomerization to isocyanates 3, which proceeds at elevated temperature, is practically the only reaction of sterically stabilized nitrile oxides. Dimerizations to 1,2,4-oxadiazole 4-oxides 4 in the presence of trimethylamine (4) or BF3 (1 BF3 = 2 1) (24) and to 1,4,2,5-dioxadiazines 5 in excess BF3 (1, 24) or in the presence of pyridine (4) are of lesser importance. Strong reactivity of nitrile oxides is based mainly on their ability to add nucleophiles and particularly enter 1,3-dipolar cycloaddition reactions with various dipolarophiles (see Sections 1.3 and 1.4). 

Some routes of chemical transformations of nitrile oxides connected with the problem of their stability were briefly discussed in Section 1.2. Here only two types of such reactions, proceeding in the absence of other reagents, viz., dimerization to furoxans and isomerization to isocyanates, will be considered. All other reactions of nitrile oxides demand a second reagent (in some cases the component is present in the same molecule, and the reaction takes place intramolecularly) namely, deoxygenation, addition of nucleophiles, and 1,3-dipolar cycloaddition reactions. Also, some other reactions are presented, which differ from those mentioned above. 

The stability of o-sulfonylbenzonitrile oxides and their thiophene analogs probably depends on electronic factors. The same factors do not prevent dimerization, as can be seen from data concerning several differently substituted nitrile oxides of the thiophene series (103). Sterically stabilized 3-thiophenecarbonitrile oxides 18 (R = R1 = R2 = Me R = R2 = Me, R1 = i -Pr), when boiled in benzene or toluene, isomerized to isocyanates (isolated as ureas on reaction with aniline) while nitrile oxides 18 with electron-withdrawing substituents (R1 and/or R2 = SOiMe, Br) dimerized to form furoxans 19. 

A related cyclization of 2-(alkynyl)phenylisocyanates with terminal alkynes to oxindoles was also reported by the same group (Equation (115)).472 (E)-exo-olefinic oxoindoles are selectively obtained. It was proposed that a palladium acetylide generated by the C-H activation of terminal alkynes regioselectively inserts to the alkyne moiety and the resulting vinylpalladium intermediate adds to the C=0 part of the isocyanate to give a (Z)-oxindole. This (Z)-isomer is isomerized to the ( )-isomer under the reaction conditions through catalysis of the phosphine. 

The acid hydrolysis of biguanides under a variety of conditions 5uelds chiefly amidinoureas the subject has been reviewed by Ray (531). The reaction proceeds slowly under very mild conditions at room temperature thus, Paludrine, when stored in 2N hydrochloric add slowly deposits N-p-chlorophenyl-N -isopropylamidinourea hydrochloride (140). That this product was not the isomeric N-isopropyl-N -p-chlorophenyl-amidinourea was verified by its rmequivocal s3uithesis from isopropyl-guanidine and p-chlorophenyl isocyanate (140) ... 

When the dramatic improvement in activity was found with the 4,6-dimethylpyrimidine heterocycle, sulfonylureas of this system were prepared from the three isomeric tolyl sulfonyl isocyanates. The para compound, which was a literature compound (Ref. 9), was devoid of activity whereas, the meta compound was found to have substantial activity. When the ortho tolyl compound was prepared, another major boost in activity was observed (Figure 10). 

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