March 1963
SUBSTRATE SPECIFICITY IS CATECHOL 0-METHYLATION
TABLEV LOGP VALUESFOR ~LISCELLANEOUS
COMPOUNDS
Compd.
Log P
C,H,C=CH CHaCOC2H5 CHsCO(CHz)aCH3 CH3CO(CH2)&H=CHz CH3COCH2CHQ-a Thiophene Indole Pyridine Quinoline Ce"B(0H)z CHaCOCH&HzCOOCHp CHaCO(CHz),COOCH3 CH,(CH?)3SCN
2.53 l t 0 . 0 1 0.32 f 0.01 1.38 f 0 . 0 1 1.02*00.01 1.50 f 0.01 1.81 f 0.01 1.14 f 0 . 0 1 0.65 & 0 . 0 1 2.03 S t 0.01 1.58f0.01 -0.23f0.02 0.55 f 0 . 0 3 2.03 f 0 . 0 2
that the logarithm of the partition of a compound in one set of solvents ( P I )is linearly related to the logarithm of the partition coefficient in a second siiiiilar set of solvents ( P 2 ) . Since RlI and A R A are ~ so readily obtained via tankless chromatography, they should prove to be valuable supplements to log P and A in the extratherniodynaniic substituent constant analysis of struct'ure-activity relationships. Experimental The part,ition coefficients were determined according to our previously reported4 procedure. llost of the compounds whose log P values are reported in Tables I and 1- were purified for
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partitioning by preparative vapor phase chromatography. Several of the compounds employed in this work have not been reported previously. l-Fluoro-3-phenylpropane.-A mixture of 1-chloro-3-phenylpropane (35 g.), dry powdered potassium fluoride (21 g.), and 120 ml. of ethylene glycol was heated at 150-160" for 12 hr. with vigorous stirring. The mixture was then cooled, diluted with water, and extracted with ether. Evaporation of the ether and fractionation of the residue yielded 11 g. of product boiling from 173-195'. This material was purified for partitioning by means of an Aerograph autoprep using a silicon column; b.p. 183.5' (730.5 mm.), n z 31.4870. ~ Anal. Calcd. for CsH,,F: C, 78.26; H, 7.97. Found: C, 78.01; H, 8.12. 2-Amino-4-phenylpentanoic acid was prepared by the malonic ester method." The melting point of our product after recrystallization from water was 245-246' dec.; von Braun and Kruber" reported 203-206". Anal. Calcd. for C11H16?;OL:C, 68.42; H, 7.76. Found: C, 68.47; H , i . 8 3 . 4-Cyclopropyl-%-butanone.--Cyclopropylmethy1 bromide was condensed with ethyl acetoacetate in the usual way.'* The resulting product was hydrolyzed with 570 KOH (yield 33Y0). The crude material was purified by vapor phase chromatography; b.p. 155" ( 7 3 2 mm.), n% 1.4260. Anal. Calcd. for C7HI20: C, 74.94; H, 10.78. Found: C, 74.89; H, 10.74.
Acknowledgment.-This work was supported under Research Grant GN-07492-04 from the National Institutes of Health. We are indebted to William McQuillan for computational assistance. (11) J. von Braun and 0. Kruber, Bel., 46, 389 (1912). (12) C. S. Marvel and F. D. Hager, "Organic Synthesis," Coll. 1'01. I. John IViley and Sons, Inc., S e a Tork, X. I-., 1911, p. 248.
The Formation of 0-Methylated Catechols by Microsomal Hydroxylation of Phenols and Subsequent Enzymatic Catechol 0-Methylation. Substrate Specificity JOHSDALY,JOSEPH I
