4-substituted phenyl isocyanates

Substituted phenyl isocyanates 266 have been prepared from the corresponding anilines 265 and triphosgene (Table 4.9) [149-151, 178]. 

Tab. 4.9. 4-Substituted phenyl isocyanates prepared with triphosgene [178].

These herbicides contain nitrogen and respond to both FID and AFID. However, the analysis of these compounds is complicated by their thermal instability. For example, the total ion current trace obtained from the GC-MS ofamethanolic solution of monolinuron shows four peaks (Fig. 9). The formation of these peaks is illustrated in Fig. 10. This thermal decomposition appears to be general for the substituted ureas and reaction of substituted phenyl isocyanates with higher alcohols also occurs. As certain substituted alkyl phenylcarbamates are used as pesticides in their own right, inert solvents such as ethyl acetate or hexane should always be used for injection. The mass spectra of the thermal... 

According to Naegeli et al. BO), the reactivity of substituted phenyl isocyanates toward amines increases in the series ... 

Figure 1. The Hammett correlation for cyclotrimerization of substituted phenyl isocyanates. Key , p-MePhNCO O, PhNCO , p-CIPhNCO T, 40°C catalyst, sodium ethoxide solvent, DMF.

In 1956, Hattori and co-workers estabUshed that aluminum azide adds to alkyl isocyanates or acid chlorides in tetrahydrofuran to afford l-aUcyl-A -tetrazoline-5-ones in excellent yields [ 101 ]. Three years later, Horwitz and coworkers reported on the synthesis of l-aryl-A -tetrazoline-5-ones by reaction of aryl isocyanates with a mixture of sodium azide and aluminum chloride in tetrahydrofiuan at reflux temperature [102]. The in situ produced aluminum azide adds to the N=C-bond of the corresponding isocyanate 122 and yields the 1-substituted A -tetrazoHne-5-one 124. According to this method, different 1-substituted A -tetrazoUne-5-ones 124 were synthesized by reaction of phenyl isocyanate and further 1-p-substituted phenyl isocyanates with aluminum azide. In addition, acyl halides 123, like acetyl chloride and benzoyl chloride, were converted to 1-methyl and 1-phenyl-A -tetrazoline-5-one with aluminum azide under the same conditions (Scheme 28A). It is assumed that in the initial step of the reaction, aluminum azide is able to coordinate to the aryl isocyanate by foiu pathways, forming an aluminum salt 129. The first two possibilities (Scheme 28B 125 and 126) require the separation of an azide ion from the complex, recombination at the electrophihc carbon atom followed... 

N-Phenyl-N -pyridinylureas, which are active as anticonvulsant agents, are prepared via substituted phenyl isocyanates by carbonylating the corresponding substituted anilines with phosgene [158]. 

Various substituted phenyl isocyanates 270 [179, 180], i.e. 2,3-dichloro-, 2,5-dichloro-, 2,6-dichloro-, 2-bromo-4-methyl-, 2,4-dibromo-, 4-chloro-2-phenoxy-, 4-butyloxy-2-chloro-, 4-chloro-2-(4-chlorophenoxy)-, 4-chloro-2-(4-chlorophenylsulfanyl)-, 4-chloro-2-[2]naphthyloxy-, 2-chloro-4-(4-chlorophenoxy)-, 2-chloro-4-trifluorome-thoxy-, 2-chloro-4-phenoxy-, 2-chloro-4-decyloxy-, 2-chloro-4-(4-chlorophenylsul-fanyl)-, 2-(4-bromophenylsulfanyl)-4-chloro-, 2,4-bis(4-chlorophenylsulfanyl)-, and 2prepared with triphosgene in dioxane at 100 °C starting from the corresponding anilines 269 [180]. 

Fluoro- and chloro-substituted phenyl isocyanates 271 have been prepared by heating the anilines tvith triphosgene and triethylamine either in benzene [179] (Table... 

A series of 5- to 8-quinolyl carbamates 653 was prepared by reacting the appropriate hydroxyquinolines with various substituted phenyl isocyanates (yields 27-92%). The procedure that gave the best results involved mixing the two reactants in diethyl ether with a catalytic amount of triethylamine and stirring at room temperature for several days [442]. 

Monoisocyanates prepared by aminolysis of phosgene are predominantly used as intermediates in the manufacture of agricultural products such as herbicides and insecticides [207, 208]. The commercially used aliphatic isocyanates include methyl, propyl, isopropyl, butyl, isobutyl, octadecyl, and cydohexyl isocyanate. The aromatic isocyanates used as building blocks for agricultural chemicals include phenyl isocyanate and halogen-substituted phenyl isocyanates. 

The reaction was also carried out with functionally substituted phenyl isocyanates and with p-phenylene diisocyanate. The reaction of diethyltin dihydride with phenyl isocyanate affords a compound with two phenyl-formamido groups attached to one tin atom. 

On the other hand, the neutral iridium(I) catalyst is also effective for construction of the C—N axial chirality. In 2012, Takeuchi et al. reported that the reactions of malonate-linked internal 1,6-diyne 29 with ortho-substituted phenyl isocyanates 30 in the presence of the neutral iridium(I)/BINAP or Hg-BINAP catalyst furnishes enantioenriched A-aryl-2-pyridones 31, having a chiral C—N axis, with good yields and ee values (Scheme 9.12) [14]. 

Substituted imidazoles can be acylated at the 2-position by acid chlorides in the presence of triethylamine. This reaction proceeds by proton loss on the (V-acylated intermediate (241). An analogous reaction with phenyl isocyanate gives (242), probably via a similar mechanism. Benzimidazoles react similarly, but pyrazoles do not (80AHC(27)24l) cf. Section 4.02.1.4.6). 

The readily available benzotriazolyl derivative of dimethyl sulfide, compound 821, can be alkylated on a-carbon in a stepwise manner to provide (a,a-disubstituted)alkyl thioethers 823 (Scheme 131). Hydrolysis of these thioethers under mild conditions (5% H2S04 at room temperature) furnishes ketones 824 in high yields. The anion derived from mono substituted (benzotriazol-l-yl)methyl thioether 822 adds to butyl acrylate to give intermediate 826 that can be hydrolyzed to y-ketoester 825. In another example of reactivity of a-(benzotriazol-l-yl)alkyl thioethers, treatment of thioether 822 with BunLi followed by phenyl isocyanate converts it into a-ketoanilide 828, via intermediate adduct 827 <1998JOC2110>. 

Amino derivatives of 1,2,4-oxadiazoles, isoxazoles, and 1,2,5-oxadiazoles interact with phenyl isocyanate to produce various 3-substituted 5-amino-l,2,4-thiadiazoles, via intermediate thioureides which can be isolated. The tendency to rearrange follows the order 1,2,4-oxadiazoles, isoxazoles, and 1,2,5-oxadiazoles <1996CHEC-II(4)307>. 

Phenyl isocyanate reacts, at room temperature, with substituted 3,4-dihydroquinazoline 108 to give the 1,3,5-triazinoquinazoline 109 by the expected [2+2+2] cycloaddition. However, at higher temperatures, the unexpected cycloadducts 110, and 111 are formed from these substrates <00EJOC2105>. 

Polymers containing pendant carbamate functional groups can be prepared by the reaction of phenyl isocyanate with poly(vinyl alcohol) in homogeneous dimethylsulfoxide solutions using a tri-ethylamine catalyst. These modified polymers are soluble in dimethyl sulfoxide, dimethylacetamide, dimethylformamide and formic acid but are insoluble in water, methanol and xylene. Above about 50% degree of substitution, the polymers are also soluble in acetic acid and butyrolactone. The modified polymers contain aromatic, C = 0, NH and CN bands in the infrared and show a diminished OH absorption. Similar results were noted in the NMR spectroscopy. These modified polymers show a lower specific and intrinsic viscosity in DMSO solutions than does the unmodified poly(vinyl alcohol) and this viscosity decreases as the degree of substitution increases. 

The condensation of isocyanate esters with diguanides proceeds in an entirely comparable manner, providing a corresponding series of s-triazin-2-ones (i.e. substituted ammelines) 378). However, since loss of water from carbamoyl-intermediates [e.g. RNHCONH C( NH)NH C( NH) -NH2] occurs much less readily than loss of hydrogen sulphide from their thiocarbamoyl-analogues, melamines are not formed in this reaction 378). The production of adducts from phenyl isocyanate and tetra-. 

Some recent work has made several heterocondensed furo[3,2-c]pyri-dines accessible. Starting compounds are the aldehydes of furo[3,2-c]pyri-dines, which are converted into the azides 203 (Scheme 75). Reaction with triphenylphosphane furnishes the iminophosphoranes 204, which are finally cyclized with phenyl isocyanate to afford the substituted pyrrolo[2, 3 4,5]-furo[3,2-c]pyridines 205 (92M807 94H1695). 

Phenyluracils with alkyl groups substituted in the 5- and 6-positions, such as (L), are reported to have analgesic and antipyretic activity [376, 377]. The 1-position may also be alkylated. Such compounds are prepared by the treatment of a-alkyl-/3-aminocrotonates with phenyl isocyanate. When the 5-substituent is an isopropyl group, the resulting compound is a sodiuretic without increase in potassium excretion. 

Carboxy substituted diazepines 226 and 229 react with phenyl isocyanate to afford pyrimido diones 227 and 230, correspondingly (Scheme 48, Section 3.1.1.3 (1993JHC897)). N-Hydroxymethylation on an indole ring annulated to benzaze-pinone, as well as formation of the corresponding carbamate and urea, has been described (2004MI1076). 

A mixture of alkyl azides, substituted phenyl isothiocyanate and aryl or alkyl isocyanate are reported to yield 5-arylamino-l,2,4-thiadiazolin-3-ones (283) via a proposed 1,2,3,4-thiatriazoline (282) (Scheme 64) <84CHEC-I(6)463>. 

Silyl-substituted diazoketones 29 cycloadd with aryl isocyanates to form 1,2,3-triazoles 194 (252) (Scheme 8.44). This reaction, which resembles the formation of 5-hydroxy-l,2,3-triazoles 190 in Scheme 8.43, has no analogy with other diazocarbonyl compounds. The beneficial effect of the silyl group in 29 can be seen from the fact that related diazomethyl-ketones do not react with phenyl isocyanate at 70 °C (252). Although the exact mechanistic details are unknown, one can speculate that the 2-siloxy-1-diazo-1-alkene isomer 30 [rather than 29 (see Section 8.1)] is involved in the cycloaddition step. With acyl isocyanates, diazoketones 29 cycloadd to give 5-acylamino-l,2,3-thiadiazoles 195 by addition across the C=S bond (252), in analogy with the behavior of diazomethyl-ketones and diazoacetates (5). 

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