Arylcarbonyl Derivatives

A relatively simple benzamide inhibitor of phosphodiesterase 4 has proven useful for treating congestive obstructive pulmonary disease (COPD). The synthesis of this compound begins by alkylation of the free phenol on aldehyde 1 with chlorodifluromethane in the presence of base. Oxidation of 

The Organic Chemistry of Drug Synthesis, Volume 7. By Daniel Lednicer Copyright 2008 John Wiley Sons, Inc. 

The discovery of the statin mevalonic acid synthesis inhibitors focused new attention on control of blood lipid levels as a measure to stave off heart disease. A number of compounds have been found that treat elevated lipid levels by other diverse mechanisms. The phosphonic acid derivative ibrolipim (9) is believed to lower those levels by accelerating fatty acid oxidation. The phosphoms-containing starting material 7 can in principle be obtained by the Arbuzov reaction of a protected from of p-bromomethylbenzoic acid (6) with triethyl phosphate. Removal of the protecting group and conversion of the acid to an acyl chloride then affords 7. Condensation of this intermediate with substituted aniline 8 leads to the hypolipidemic agent (9).  

An aryl carbamate replaces the tyrosine moiety in a related analogue. The preparation of this compound first involves activation of the side-chain oxygen in the same oxazole used above (21) by conversion to its mesylate (21a) by means of methanesulfonyl chloride. This intermediate 

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In the same way as changes in reactivity reflect the nature of the transition state, a change in equilibrium constant corresponds to a change in the thermodynamic stability of the carbocation intermediate. For example, substituent effects on the basicities of arylcarbonyl derivatives ArCOR provide a reference for the formation of a-hydroxycarbocations (17). 

Cyclization of 6-(arylcarbonyl)methyl-2-aryl-77/-naphtho[l,2,3-with hydrazine hydrate gave 1,2-diazepine derivatives 61 <2003AJC1219> (Equation 6). 

Special Coupling Partners Phenol Derivatives and Arylcarbonyl Compounds... 

Arylcarbonyl isothiocyanates react with A,A-disubstituted hydrazones 188 to give 1,3,5-oxadiazine derivatives 189 . 

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