[Hydrophobic constant values (delta RMO) of functional groups. II. Interpretation of fragment interactions].
The delta RM0(-CH2-) values have been calculated from fragment values of various alkyl groups (methyl, ethyl, n-propyl). On the basis of delta RM0(-CH2-) values it has been established that the value of the so-called "second" methyl group from aromatic ring has slightly differed from that of the so-called third methylene group and the value of methylene functional group is constant independently from positions of substituents and from electronic interactions. The delta RM0 Me values of methyl group--which is directly attached to aromatic ring--have been regarded as the so-called first methylene group from aromatic ring since value of free energy needed for transfer of methyl group as well as the other physico-chemical data (mole volume, parachor) are nearly the same as those of methylene group according to the literature. Fragment values of methyl groups substituted at various positions have been compared to relating delta RM0(-CH2-) value which is free practically from electronic interactions and it has been ascertained that fragment values have been higher as well as lower. In accordance with literature lower delta RM0 Me values have been interpreted with hyperconjugation effect of aromatic system. On the other hand lower methylene fragment values of alkyl substituted compounds at N1 atom have been attributed to sigma conjugation. In literature higher delta RM0 Me values than relating delta RM0(-CH2-) value are known only in case of orto position to another functional group or by a methyl group on a sterically hindered aromatic ring. Results of tests have shown that values of delta RM0 Me can substantially increase with extension of conjugated aromatic system or with simultaneous substitutions of methyl, methylene groups, respectively at certain locations. The authors have assigned that increase to change of solvate cuver which surrounds the molecule. The same has been manifested by methyl fragment values of quinazoline derivates (tetrahydropyrroloquinazoline, hexahydroazepinoquinazoline) of different electronic distributions. On basis of calculations it has been proved that delta RM0 2-Me and delta RM0 6-Me fragment values of monosubstituted pyrido (1,2-a)-pyrimidine (PP) derivatives have significantly differed from delta RM0 Me values of at other positions (3,7,8,9) methyl substituted compounds. Among disubstituted derivatives only delta RM0 7-Me and delta RM0 8-Me values of 2-phenyl- and 3-carbetoxymethyl-PP derivatives have not differed from each other but methyl fragment values of other positions (6,9) have significantly differed from each other and from other fragment values too.(ABSTRACT TRUNCATED AT 400 WORDS)
Vámos
J
J
Semmelweis OTE Gyógyszerészi Kémiai Intézet, Budapest.
Kapolka
P
P
Szász
G
G
Józan
M
M
D055598:Chemical Phenomena; D002621:Chemistry; D006838:Hydrocarbons; D011083:Polycyclic Compounds; D013329:Structure-Activity Relationship
D006838:Hydrocarbons; D011083:Polycyclic Compounds
Funkciós csoportok hidrofób konstans értékeinek (delta RM0) vizsgálata. II. Fragmens interakciók értelmezése.