Novel syntheses of the methoxy isoquinolines and isocoumarins

Directed metalation reactions. 6. Competition of substituents for ortho direction of metalation in substituted anisoles

“…However, certain of the meta and ortho compounds were accessible only through rather complicated synthetic routes and in most of these cases it was felt that examination of these compounds would lend little to the study. In all, 16 of the isomers including all the para isomers and representative meta and ortho compounds were prepared: p-,m-, and 0-methoxy-N,N-dimethylaniline (1, 2, and 3, respectively), p-, m-, and 0-methoxy-N,N-dimethylbenzylamine (4, 5, and 6, respectively), p-and o-methoxy-N./V-dimethylphenethylamine (7 and 8, respectively), p-, m-, and 0-methoxy-IV-methylbenzamide (10,11, and 12, respectively), p-methoxy-W-methylbenzenesulfonamide (15), p-methoxy-7V,/V-dimethylbenzenesulfonamide (16), pmethoxybenzotrifluoride (17), andp-and o-fluoroanisole (18 and 19, respectively). These compounds were obtained by either the synthetic procedure or from the commercial source given in the Experimental Section.…”

“…-S02NMe2. As shown in Table III, metalation of p-methoxy-Ar,Ar-dimethylbenzenesulfonamide (16) with n-butyllithium indicated that the dimethylsulfonamide substituent was a better ortho-directing substituent than the methoxy substituent. Proof of the site of metalation was based on NMR integration of the deuterated product obtained from hydrolysis of the lithio intermediate of sulfonamide 16 with D20.…”

“…As shown in Table III, metalation of p-methoxy-Ar,Ar-dimethylbenzenesulfonamide (16) with n-butyllithium indicated that the dimethylsulfonamide substituent was a better ortho-directing substituent than the methoxy substituent. Proof of the site of metalation was based on NMR integration of the deuterated product obtained from hydrolysis of the lithio intermediate of sulfonamide 16 with D20. Sulfonamide 16 exhibited an NMR spectrum having a well-resolved AA'BB' pattern in the 2.68 region representing the aromatic protons assignments for which were analogous to those of sulfonamide 15.…”

Parametrization of Substituents: Effects of Fluorine and Other Heteroatoms on OH, NH, and CH Acidities

“…When treated with butyllithium in diethyl ether, (4-methoxybenzyl)dimethylamine undergoes a lithium/hydrogen exchange cleanly at a position adjacent to the nitrogen-bearing side chain (Scheme 3). [85] However, in the presence of N,N,N',N'-tetramethylethylenediamine (TMEDA) the same reagent attacks preferentially, though not exclusively, the aromatic sites in the immediate vicinity of the methoxy group (regioisomeric ratio % 1:8) [86,87] (Scheme 3).…”

Parametrisierung von Substituenten – der Einfluß von Fluor und anderen Heteroatomen auf OH-, NH- und CH-Aciditäten

“…Deprotonierungsgeschwindigkeiten von 1-Fluor-3-halogenbenzolen: [a] [77] In Gegenwart von N,N,N',N'-Tetramethylethylendiamin (TMEDA) greift das gleiche Reagens jedoch vorwiegend die o-Positionen der Methoxygruppe an (Regioisomeren-Verhältnis $ 8:1). [86,87] Schema 3. Wahlweise Positionsselektivität bei der Metallierung von (4-Methoxybenzyl)dimethylamin.…”