Chloromethyl with phenolates

CMoromethyUuion of mtrophenols.2 o-Nitrophenols and, in some instances, p-nitrophenols can be chloromethylated with the reagent. The reaction fails with dinitro-phenols. A catalyst (zinc chloride) is required for the reaction. 

When a side chain also contains a halogen atom, such as in l,l-dichloro-2-(chloromethyl)cy-clopropane (22) or 2-(bromomethyl)-l,l-dichlorocyclopropane, elimination can occur to give a methylenecyclopropane followed by two elimination-addition cycles. The elimination-addition products are accompanied by variable amounts of substitution products in which the two chlorine atoms on the ring remain intact. Thus, for example, reaction of 22 with phenolate under phase-transfer conditions gives 10% of the substitution product 24 along with 73.5% of the double-addition product, 2-methylene-l,l-bis(phenoxy)cyclopropane (23). Bulkier nucleophiles, such as those derived from 2-phenylpropanenitrile and diphenylacetonitrile, do not add twice to the same carbon atom and give 88 and 46% yield of the 2,3-bisadducts 25, respectively. 

A mixture of ethyl 2-chloromethyl-4-nitrophenyl hydrogen phosphate and 2 equivalents n-pentanol in 5 equivalents pyridine stored 2 days at room temp., then heated 6 hrs. at 90° ethyl n-pentyl hydrogen phosphate. Y 81%. F. e., also with phenols, s. T. Hata, Y. Mushika, and T, Mukaiyama, Tetrah. Let. 1970, 3505 Bull. Chem. Soc. Japan 44, 232 (1971) Chem. Pharm. Bull. 19, 687, 696 (1971). 

In 1932, Quelet used the Blanc procedure, replacing formaldehyde with aliphatic aldehydes in the reaction with phenolic ethers. The resulting reaction mixtures were found to contain a-chloroalkyl derivatives. Although the conditions are virtually identical and the reaction proceeds via the same basic mechanism, the Blanc chloromethylation is often referred to as the Quelet reaction. 

Borman was able to synthesize the chloromethyl derivative by carrying out the chlorination reaction with chlorine in the presence of phosphorus trichloride. Up to 85% of the chlorination occurred on the methyl groups. These polymers were reacted with phenol and the resulting phenolic materials could be readily cross-linked using phenol-formaldehyde chemistry. Chlorinated polymers were also obtained by chlorination in the presence of AICI3 and FeClj and under UV irradiation. Severe degradation of the polymer chain occurred in all these cases. 

Platinum-group metals (qv) form complexes with chelating polymers with various 8-mercaptoquinoline [491-33-8] derivatives (83) (see Chelating agents). Hydroxy-substituted quinolines have been incorporated in phenol—formaldehyde resins (84). Stannic chloride catalyzes the condensation of bis(chloromethyl)benzene with quinoline (85). 

To support a polystyrene onto the upper rim of ca-lix[4]arene (phenolic-O- of calix[4]arene) and 25,26,27-tribenzoyloxy-28-hydroxy, calix[4]arene was treated with chloromethylated polystyrene in the presence of K2CO3 (Scheme 7). Polymeric calix[4]arene (3a) thus obtained was hydrolyzed in the benzoyl groups prior to use for the extraction process. 

Lee [42] determined pentachlorophenol and 19 other chlorinated phenols in sediments. Acidified sediment samples were Soxhlet extracted (acetone-hexane), back extracted into potassium bicarbonate, acetylated with acetic anhydride and re-extracted into petroleum ether for gas chromatographic analysis using an electron capture or a mass spectrometric detector. Procedures were validated with spiked sediment samples at 100,10 and lng chlorophenols per g. Recoveries of monochlorophenols and polychlorophenols (including dichlorophenols) were 65-85% and 80-95%, respectively. However, chloromethyl phenols were less than 50% recovered and results for phenol itself were very variable. The estimated lower detection limit was about 0.2ng per g. 

Chemical/Physical. Anticipated products from the reaction of benzyl chloride with ozone or OH radicals in the atmosphere are chloromethyl phenols, benzaldehyde and chlorine radicals (Cupitt, 1980). 

Silyl derivatives containing halogens have been used, as for other substances, also for carboxylic acids with sensitive electron-capture detection. Chloromethyldimethylsilyl derivatives have been applied to phenolic acids, as follows [176], An amount of 1 mg of phenolic acids was dissolved in pyridine (600 pi), bis(chloromethyl)tetramethyldisilazane (200 pi) and chloromethyldimethylchlorosilane (100 pi). The mixture was diluted with w-hexane after 30 min and 0.1 -0.2 pi was analysed (UCW-98,200°C). The limit of detection was reported to be 4 ng. 

Phenolic and acidic pesticides and herbicides were chromatographed as chloromethyl and bromomethyldimethylsilyl derivatives [502] and the entire procedure was applied to the analysis of these substances in soil, as follows. A 1-ml volume of n-hexane, 0.075 ml of dimethylamine and 0.09 ml of halomethyldimethylchlorosilane were mixed in a 5-ml vial, which was then closed and shaken vigorously. The mixture was centrifuged and 0.4 ml of the supernatant was transferred into an 8-ml test tube and 0.1 ml of ethyl acetate containing 100 jug of the substrate was added. The contents were refluxed for 30 min at 65°C, cooled and the reflux condenser was rinsed with 0.5 ml of n-hexane. 

We have already seen how salicylic acid can be made by reaction of the sodium salt of phenol (PhONa) with C02. More important than these reactions is chloromethylation, a way of adding a single carbon atom at the alcohol oxidation level. A combination of formaldehyde (CH2=0) and HCl provides the one-carbon electrophile. 

Note 3. Temperature control is critical during the initial reaction in the ice bath and in the standing afterward. The purity of the crude product is drastically reduced if the reaction mixture ever reaches temperatures above ca. 35°C deep red gums are formed. The color is no doubt due to condensation of the chloromethyl compound with salicylaldehyde acting as a phenol to give aurin-like triarylmethyl dyestuffs see Note 1. 

Proticlion of hydroxyl groups. f-Butoxymethyl ethers of alcohols can be obtained by rcaclion with <-butyl chloromethyl ether and triethylamine in THF at room tempcralure. The acetals are obtained in 55-80% yield. Yields are poor in the case of phenols. Deprotection is accomplished with TFA at room temperature. The acetals are stable to hot acetic acid therefore selective deprotection of other acid-sensitivc groups is possible. ... 

Reactions of (a-chloromethyl) thiiranes with sodium phenolate in various solvents were investigated <2003RJ0226>. Reaction of 2-(chloromethyl) thiirane-3,3-42 with PhONa in 85% EtOH gave a mixture of the labeled (phenoxymethyl) thiiranes 190 and thietane 191 in 30% yield, as a 5 2 mixture of 190 191 (Scheme 44). 

Cs-X has also been used to promote the selective O-methylation of phenol with dimethyl carbonate. 2 N-Monomethylaniline was obtained in 93% yield by reacting aniline with dimethyl carbonate over a K-Y catalyst at 180°C (Eqn. 22.46). 3 The reaction of alcohols with chloromethyl ether over Na-Y gave the resulting methoxymethyl ethers in 70%-90% yields (Eqn. 22.47). 4... 

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