Disubstituted benzophenones

Kinetic evidence for the involvement of a-hydroxydialkylnitrosamines (142) in the pH-independent solvolysis of the a-(acyloxy)dialkylnitrosamines (141) has been obtained.120 The aminolysis in benzene of 0-(2,4-dinitrophenyl)-/7,/ -disubstituted benzophenone oximes (143) with pyrrolidine and piperidine are third order in amine.121 Hir st s mechanism involving electrophilic catalysis operates and can explain the various effects observed. The bis(pentamethylphenyl)-A-isopropylketenimine (144) undergoes pre-equilibrium /V-protonation in aqueous acetonitrile followed by water attack. An inverse solvent isotope effect and the observation of the diol (145) confirm this.122... 

A new synthesis of sterically hindered o-substituted tetraphenylethenes via McMurry olefination of the corresponding 2,2 -disubstituted benzophenones exploits electronic effects that dominate over steric considerations.187... 

Kong, F.F., Zhai, B.C., and Song, Q.-H. (2008) Substituent effects on the regioselective formation of the Patemd-Biichi reaction of 5- or/and-6-methyl substituted uracils with 4,4 -disubstituted benzophenones. Photochemical el Photobiological Sciences, 7, 1332-1336. 

IMI has also developed a general route for the synthesis of homo- and hetero-disubstituted benzophenones such as 4,4 -difluorobenzophenone (DFBP), 4,3 -di-fluorobenzophenone, and 4,4 -diphenoxybenzophenone (DPOBP). These substituted benzophenones are important materials, with a variety of uses as specialty monomers (for polyether ketones and polyarylene ether ketones) and pharmaceutical intermediates. These benzophenones are prepared by utilizing Heck technology in conjunction with an oxidative cleavage reaction. 

Eisenstadt, A. and Effenberger, R., Process for the preparation of disubstituted benzophenones , Israel application 115855 (1995) b. Eisenstadt, A. and Maidan, R., personal communication (1993). 

Interest continues in the use of disulfonating agents for carrying out selective disubstitutions. Benzophenone 3,3 -disulfonyl imidazole reacts only with the 0-2 hydroxyl groups on adjacent glucose units of y-CD, while the corresponding derivative of 1,4-dibenzoylbenzene reacts with 0-2 0-2 of p-CD to give 24% of the cyclic diester with 3% and 1% of the 2 2 and 2 2 derivatives respectively. ... 

In addition, IMI developed a route to disubstituted benzophenones based on a heterogeneously catalyzed Heck reaction in conjunction with an oxidative cleavage reaction. As an example, the synthesis of 4,4 -difluorobenzophenone, which is used as a monomer for polyether ketones, has been performed by a double Heck reaction of 4-fiuorobromoben-zene with 2-ethylhexyl acrylate. Subsequent oxidative cleavage of the double adduct yields the desired product. ... 

A procedure for preparing 4,4 -disubstituted benzophenones 1266 using oxalyl chloride was described by Cram [952]. 

The ruthenium-, rhodium-, and palladium-catalyzed C-C bond formations involving C-H activation have been reviewed from the reaction types and mechanistic point of view.135-138 The activation of aromatic carbonyl compounds by transition metal catalyst undergoes ortho-alkylation through the carbometallation of unsaturated partner. This method offers an elegant way to activate C-H bond as a nucleophilic partner. The rhodium catalyst 112 has been used for the alkylation of benzophenone by vinyltrimethylsilane, affording the monoalkylated product 110 in 88% yield (Scheme 34). The formation of the dialkylated product is also observed in some cases. The ruthenium catalyst 113 has shown efficiency for such alkylation reactions, and n-methylacetophenone is transformed to the ortho-disubstituted acetophenone 111 in 97% yield without over-alkylation at the methyl substituent. 

As mentioned above, Eisch and co-workers have synthesized new methylidene-group IV metal complexes, such as the methylidene zirconium complex 88 from zirconium(iv) chloride and 2 equiv. of methyllithium at low temperature (Scheme 36).53 By using this reagent, benzophenone was easily converted at low temperature into the desired 1,1-disubstituted alkene in quantitative yield. 

The iV-lithio-2-phenyl- 1,2-dihydro adduct (515) (Section 3.2.1.6.8.i) is a useful synthetic intermediate that reacts with alkyl halides, bromine (70CC478), carbon dioxide (70TL3371) and benzophenone (70CC921) to give 2,5-disubstituted derivatives. 

Metal acetylacetonates quench triplet species generated by flash photolysis of aromatic ketones and hydrocarbons.330-333 More recently, these reactions have been studied from a synthetic standpoint. Triplet state benzophenone sensitizes photoreduction of Cu(MeCOCHCOMe)2 by alcohols to give black, presumably polymeric, [Cu(MeCOCHCOMe)] . This reacts with Lewis bases to provide complexes of the type CuL2(MeCOCHCOMe) (L = bipyridyl/2, ethylenediamine/2, carbon monoxide, Ph3P). Disubstituted alkynes yield Cu(C2 R2 XMeCOCHCOMe) but terminal alkynes form CuQR acetylides.334 The bipyridyl complex of copper(I) acetylacetonate catalyzes the reduction of oxygen to water and the oxidation of primary and secondary alcohols to aldehydes and ketones.335... 

Reaction of N -phenylthioformhydrazine (73) with ketones in the presence of trimethylsilyl chloride at room temperature gave 2,2-disubstituted-2,3-dihydro-3-phenyl-l,3,4-thiadiazoles (74) in good yield, except with benzophenone and a,P-unsaturated ketones. O-Trimethylsilyl... 

Some trisubstituted ozonides could be obtained only by the method of Murray, Story, and Loan (1)—namely, the ozonization of disubstituted olefins in ketones as solvents. Ozonization of tetraphenylethylene in acetone, methyl ethyl ketone, or benzophenone gave the hitherto unknown trioxolanes with four hydrocarbon residues (2). Table I shows some examples. 

Under similar conditions, treatment of 15a with Me3SiCl, I2 or NBS provided the 2,7-disubstituted derivatives 15d, 15e, and 15f, respectively in 24—31% yield. The formylation of 15a with DMF seemed to be more effective and the 2,7-dicarbaldehyde 15g was obtained in 59% yield. Similarly, 15b afforded 15h in 53% yield, suggesting that the presence of the methyl groups did not affect the formation of the dianion. Treatment of 15a with benzophenone produced 15i in 51% yield and when benzaldehyde was used as an electrophilic reagent, two diastereoisomers were formed one with U2 symmetry and the other without a symmetrical axis (Scheme 29) <2002J(P1)1963>. 

The approach previously outlined in Scheme 8 was used to generate numerous TV, d-disubstituted isoquinuclidines. Red-Al reduction of the lactam (83) and subsequent oxidation of the hydroxyl groups to ketones 134 was achieved via a modified Oppenauer procedure [108] using benzophenone and potassium butoxide and was accomplished in 90 minutes and in fair yields. 

With less-reactive aromatics, a stronger Lewis acid may be required, but the monosubstimted acyl chloride can be isolated. Under appropriate conditions, a symmetric, disubstituted ketone is formed. Thus, benzophenone can be isolated by the reaction with excess benzene (Wilson and Fuller, 1922). 

Electrophilic substitution is difficult with electron-deficient heteroatomic compounds such as pyridine and quinoline. However, an electrophile can be readily introduced when the heterocycles have an effective ortho-directing group such as a sulfamoyl moiety. Lithiation of the 2-pyridinesulfonamide (51) was performed at low temperature by using 2 equivalents of LDA in ether at —78 °C for 1.5 h (equation 27). Addition of benzophenone to the solution of 52 gave the adduct in high yield38. Metallation of the 4-pyr-idinesulfonamide 53 with 3 equivalents of LDA, followed by reaction with benzaldehyde, afforded the 3,5-disubstituted pyridine 54 (equation 28). 

Other polymers which have been the subject of thermal degradation studies include ethylene-vinyl acetate [29, 66, 67], ethylene-vinyl alcohol [68], poly(aryl-ether ketone) [69], poly-2-vinyl-naphthalene-co-methyl maleate [34], polyphenylenes based on diethyl-benzophenone [70], polyglycollide [71-73], poly(a-methylstyrene tricarbonyl chromium [74], polytetrahydrofuran [75], polylactide [76-78], poly(vinyl) cyclohexane [79], styrene-vinyl cyclohexane [80], isopropenylacetate-maleic dianhydride [80], polyethylene glycol containing a 1,3-disubstituted phenolic group [81], poly-2-vinyl naphthalene-co-methacrylate [34], collagen biopolymers [82], chitin graft poly (2-methyl-oxazoline - polyvinyl chloride blends [83], cellulose [32, 83-88] and side-chain cholestric elastomers [89, 90]. 

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