Hydroxybenzophenone synthesis

Benzotrichloride and BC are, however, efficiently utilized for small-scale hydroxybenzophenone synthesis. Thus benzoylation of phenol can be simply performed by stirring at 120°C for 5 h an equimolecular mixture of phenol and benzotrichloride in the presence of ZSM-5 in 1,2-dichloro-ethane. 4-Hydroxybenzophenone is obtained in 80% yield, whereas by using BC under the same reaction conditions, the same product is isolated in 67% yield. 

Alkylation of 4-hydroxybenzophenone by means of base with 2-ihlorotriethylamine affords the so-called basic ether (29). In a lequence analogous to the preparation of 28, the ketone is first reacted with benzylmagnesium chloride (30). Dehydration (31) and rlilorination complete the synthesis of clomiphene (32). ° It is itf note that the commercial product is in fact a mixture of the... 

The consecutive formation of o-hydroxybenzophenone (Figure 3) occurred by Fries transposition over phenylbenzoate. In the Fries reaction catalyzed by Lewis-type systems, aimed at the synthesis of hydroxyarylketones starting from aryl esters, the mechanism can be either (i) intermolecular, in which the benzoyl cation acylates phenylbenzoate with formation of benzoylphenylbenzoate, while the Ph-O-AfCL complex generates phenol (in this case, hydroxybenzophenone is a consecutive product of phenylbenzoate transformation), or (ii) intramolecular, in which phenylbenzoate directly transforms into hydroxybenzophenone, or (iii) again intermolecular, in which however the benzoyl cation acylates the Ph-O-AfCL complex, with formation of another complex which then decomposes to yield hydroxybenzophenone (mechanism of monomolecular deacylation-acylation). Mechanisms (i) and (iii) lead preferentially to the formation of p-hydroxybenzophenone (especially at low temperature), while mechanism (ii) to the ortho isomer. In the case of the Bronsted-type catalysis with zeolites, shape-selectivity effects may favor the formation of the para isomer with respect to the ortho one (11,12). 

The polyetherification route to polyethersulfones can be adapted to the synthesis of polyethers containing strongly electron-withdrawing groups other than sulfone groups. Poly(l,4-oxyphenylenecarbonyl-l,4-phenylene) [27380-27 4] (6) is produced by condensation of 4,4 -dihydroxybenzophenone or by the self-condensation of 4-chloro-4 -hydroxybenzophenone. It has a melting point of 367°C and a glass-transition temperature of 154°C (83). 

The cyclization of 2-hydroxybenzophenones is a well-documented procedure for the synthesis of xanthones < 1984CHEC, 1996CHEC-II>. Xanthone 799 is a key intermediate during the synthesis of gambogin and can be accessed in high yield via cyclization of the corresponding 2-hydroxybenzophenone derivative (Equation 332) <2005AGE756>. 

Chaube, V. D., Moreau, P., Finiels, A., Ramaswamy, A. V., and Singh, A. R, A novel single step selective synthesis of 4-hydroxybenzophenone (4-HBP) using zeolite H-beta. Catal. Lett., 2002, 79, I 4. 

Thermal dehydration of o- (acylamino)phenols is the method of choice for the preparation of benzoxazoles (equation 96) and other annulated oxazoles. 0,iV-Diacyl derivatives of o-aminophenols cyclize at lower temperatures than do the monoacyl compounds. The synthesis is often carried out by heating the aminophenol with the carboxylic acid or a derivative, such as the acid chloride, anhydride, an ester, amide or nitrile. The Beckmann rearrangement of oximes of o-hydroxybenzophenones leads directly to benzoxazoles (equation 97). 

Light stable PUR 111 was created by incorporation of 4-(2,3-dihydroxyprop-oxy)-2-hydroxybenzophenone during PUR synthesis [139]. Similarly, urethane based coatings may be stabilized by immobilization of approx. 5% of 4-hydroxy-5-tert-butyl-3-[2-(5-chlorobenzotriazolyl)]methyl-isocyanate, added into the reaction mixture during PUR synthesis [140]. 

Kulka " developed a synthesis of o-hydroxybenzophenones in which a t-butyl group is used to block the para position of a phenol methyl ether to permit o-benzoylation and is then removed, along with the ether group, with aluminum chloride. 

Synthesis of 3-substituted benzo[fc]furans was realized from a combination of benzotiiazole chloride mediated intramolecular cyclization and low-valent titanium promoted reduction. Thus, the sodium salt of 2-hydroxybenzophenone was first allowed to react with a 1-benzotriazol-l-ylalkyl chloride to give a ketone which was cyclized by LDA. Eventually, A titanium promoted elimination led to the desired 3-phenylbenzo(I>]furan in good yield <01JOC5613>. 

Hydroxylated aromatic ketones represent valuable intermediate compounds in the synthesis of important fragrances and pharmaceuticals. For example, the resorcinol acylation products are employed for the production of valuable fine chemicals such as 4-0-octyl-2-hydroxybenzophenone (UV light absorbent for polymers) and ipriflavone (antiosteopenic drug). a-Hydroxyacetophenone (o-HAP) and p-hydroxyacetophenone (p-HAP) are widely used for the synthesis of aspirin and paracetamol (4-acetaminophenol), respectively [103]. a-HAP represents also a key intermediate for the production of 4-hydroxycoumarin and warfarin, which are both used as anticoagulant drugs in the therapy of thrombotic disease [104], and it is also employed for the synthesis of flavo-nones [105,106]. 

Preparation from thioxanthen-9-one 10,10-dioxide (SM) by a three-steps synthesis refluxing SM in 2% sodium hydroxide-65% dioxane-water solution for 4 h gave the 2-(2-hydroxybenzoyl)-phenylsulfinic acid (25%). The former, by reaction with mercuric chloride in refluxing aqueous acetic acid for 4 h, led to the 2-chloromercuri-2 -hydroxybenzophenone (69%). Removal of the chloromercury group was achieved with concentrated hydrochloric acid in refluxing ethanol for 2 h (91%) [62],... 

Iaroshenko VO, Savych I, VUlinger A, Sosnovskikh VY, Langer P (2012) Reactions of 3-acylchromones with dimethyl 1,3-acetonedicarboxylate and 1,3-diphenylacetone one-pot synthesis of functionalized 2-hydroxybenzophenones, 6i/-benzo[c]chromenes and benzo[c] coumarins. Org Biomol Chem 10 9344-9348... 

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