Hydroxyphenyl Ureas

Chemical Name [5-[2-[(1,1 -Dimethylethyl)amino]-1-hydroxyethyl] -2-hydroxyphenyl] urea Common Name —... 

CASRN 1982-49-6 molecular formula C14H20N2O FW 232.30 Soil. A fungus and two Pseudomonas spp. isolated from soil degraded siduron to form the major metabolites l-(4-hydroxy-2-methylcyclohexyl)-3-(p-hydroxyphenyl)urea, l-(4-hydroxy-2-... 

In the host lattice of 24, the rhodizonate dianion resides at an inversion center, being directly linked to a pair of A -(3-hydroxyphenyl)urea molecules through pairs of N-H- -0 [A, N2 = R 9)] and phenyl C-H- -0 [B, N2 = f 2(6)] hydrogen bonds... 

Chemat et al. have reported several microwave reactors, including systems that can be used in tandem with other techniques such as sonication [68], and ultraviolet radiation [69]. With the microwave-ultrasound reactor, the esterification of acetic acid with n-propanol was studied along with the pyrolysis of urea. Improved results were claimed compared with those from conventional and microwave heating [68]. The efficacy of the microwave-UV reactor was demonstrated through the rearrangement of 2-benzoyloxyacetophenone to l-(2-hydroxyphenyl)-3-phenylpropan-l,3-dione [69]. 

There are few cases in which free /3-aldehydo esters have been condensed successfully with ureas. Commonly, alkoxymethylene esters are used. The initial reaction leads to an acyclic intermediate that may require a separate treatment to induce ring closure. The reaction of a /3-keto ester with urea may be a two-step process in which case acid catalysis can be used in the formation of an acyclic intermediate, with ring closure effected by strong alkali. When the ester component is a lactone or chromone, the product contains a hydroxyalkyl <2000JME3837> or 2-hydroxyphenyl substituent <2004S942>, as shown by the synthesis of the 5-(2-hydroxyethyl)-4-pyrimidinone 657 and the 6-(2-hydroxyphenyl)-pyrimidine 659. 

Simple side-chain reactions of 1,2-dithiin diols have been conducted. Besides the formation of esters, ethers (R = Me, Et, 7-Pr, cyclopropyl, Ph, pyridyl, cyclopentyl), and thioethers (R = H, TBDMS R = 4 -(4-hydroxyphenyl)-l//-tetrazole-5-thiol), selective oxidation of the primary alcohol groups in the presence of the 1,2-dithiin heterocycle could be readily achieved (Scheme 36) <1995JME2628, 1994SL201>. Additionally, amides, ureas, and carbamates of the dithiin diol were synthesized <1995JME2628>. 

Here, the authors treated phenylethylaniine 35 with 1.25 equiv. of 4-methox-yphenyl isocyanate 36 to form a crude reaction mixture of product urea 37 and excess isocyanate. Subsequently, the isocyanate impurity was removed either by quenching with N,N-dimethylaminoethylamine followed by cation exchange, or by quenching with 1-(2-hydroxyphenyl) piperazine followed by anion exchange. 

Other amino acid derivatives, such as a-hydroxy acids and cyanohydrins, also react with urea to give hydantoins,1 e.g., the synthesis of 5-(4-hydroxyphenyl)hydantoin.31... 

D-p-Hydroxyphenyl glycine is a key raw material for the semisynthetic penicillins such as ampidllin and amoxycillin. It is also used in photographic developers. Racemic hydantoins are synthesized starting from phenol derivatives, glyoxylic acid and urea via the Mannich condensation (Fig. 19-28). The D-specific hydantoinase is applied as immobilized whole cells in a batch reactor. The unreacted L-hydantoins are readily racemized under the alkaline conditions (pH 8) of enzymatic hydrolysis, yielding quantitative conversion. This process enables the stereospecific preparation of various amino acids, such as L-tryptophane, L-phenylalanine, D-valine, D-alanine... 

The base-induced ring rearrangement of l-(5//-[l]benzopyrano[2,3-A]pyridin-5-yl)-l,3-dimethyl-urea with lithium diisopropylamide at — 40 to 25°C leads via the anion to l,3-dimethyl-4-(2-hydroxyphenyl)-3,4-dihydropyrido[2,3-d]pyrimidin-2(l//)-one (l).280 The reaction involves the intramolecular substitution of the phenoxy group by the urea anion at the 2-position of the pyridine moiety. 

N- [2- ( 3,5-DI-tef -BUTYL-4-HYDROXYPHENYL ) ETHYL] N -(4-AZIDOSUL-fonylphenyl) urea (DTBSU). 4-Isocyanatobenzenesulfonyl azide (11.2 g, 0.05 mol) and dry acetonitrile (200 mL) were placed in a 500-mL three-necked flask fitted with a thermometer, stirrer, and drying tube. The flask was maintained at 20-25°C and 12.4 g (0.055 mol) of 2-(3.5-di-ter -butyl-4-hydroxyphenylethylamine (19) dissolved in 200 mL acetonitrile were added slowly. After 2 hr of stirring at room temperature ir spectrophotometric examination of an aliquot indicated complete loss of the isocyanate function. The acetonitrile was removed in a rotary evaporator and the remaining material poured into ice to precipitate the product in an 87% yield. The product melted at 122-127°C and evolved nitrogen at 140-150 °C. The ir spectrum contains bands at 3210 cm 1 (NH), 2120 cm 1 (azide), 1675 cm 1 (amide carbonyl), and 1160 cm 1 (sulf one). 

Hydroxyphenyl)hydantoin was formed, with avoidance of the use of sodium cyanide, in 61% yield, by the addition of a mixture of phenol, urea, water and concentrated hydrochloric acid to stirred 50% aqueous methyl 2-hydroxy-2-methoxyacetate at 70" C followed by further reaction during 10 hours (ref.48). 

The stabilizer systems for polyacetals are invariably composed of a hindered phenol with a costabilizer. The hindered phenols in use are 2,2 -methylenebis-(4-methyl-6-tert-butyl-phenol), 1,6-hexamethyle-nebis-3-(3,5-di-rert-butyl-4-hydroxyphenyl)-propionate, and pentaerythrityl-tetrakis-3-(3,5-di-fert-butyl-4-hydroxyphenyl)-propionate. A large number of nitrogen-containing organic compounds have been described as costabiKzers for polyacetals, e.g., dicyandiamide, melamine, terpolyamides, urea, and hydrazine derivatives. The effectiveness of these compounds is based on their ability to react with formaldehyde and to neutralize acids, especially formic acid, formed by oxidation. In addition to nitrogen compounds, salts of long-chain fatty acids (e.g., calcium stearate, calcium ricinoleate, or calcium citrate) are also used as acid acceptors. The practical concentrations are 0.1-0.5% for the phenolic antioxidant and 0.1-1.0% for the costabilizer. 

Likewise, the intramolecular oxidative coupling of substituted 4-hydroxyphenyl-A(-phenylbenzamides 72 has been realized in a catalytic manner by using iodobenzene as catalyst and mCPBA or urea-H202 as terminal oxidant (Scheme 4.37). This reaction constitutes an efficient method for the synthesis of spirooxindoles 73 [69],... 

Photolytic. When an aqueous solution of linuron was exposed to sununer sunlight for 2 months, 3-(3-chloro-4-hydroxyphenyl)-l-methoxy-l-methylurea, 3,4-dichlorophenyl-urea and 3-(3,4-dichloropheityl)-l-methylurea formed at yields of 13, 10 and 2%, respectively. The photolysis half-life of this reaction was approximately 97 days (Rosen et al., 1969). In a more recent study, Tanaka et al. (1985) studied the photolysis of linuron (75 mg/L) in aqueous solution using UV light (X = 300 nm) or sunlight. After 24 days of exposure to sunlight, linuron degraded to a trichlorinated bipheityl (1% yield) with the concomitant loss of hydrogen chloride (Tanaka et al., 1985). 

Fig. 16.14 Chromatogram of organic acids extracted using solvents from the urine of a patient with hereditary tyrosinaemia and separated as their methoxime and tri-methylsilyl derivatives on 3 per cent OV-17 using temperature programming from 80°C to 260°C at 4°C min Peak identifications are 1, urea plus phosphate 2, succinate 3, 2-methyl-3-hydroxybenzoate (internal standard) 4, 2-oxoglutarate 5, 4,6-dioxo-heptanoate (succinylacetone) 6, 4-hydroxyphenylacetate 7, aconitate 8, citrate 9, isocitrate 10, dihydroxyphenylpropionate 11, 4-hydroxyphenyl-lactate 12, 4-hydroxyphenylpyruvate 13, 3,5-dioxo-octanedioate (succinylacetoacetate). (Redrawn with modifications from Lindblad etal, 1977)...

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