1.2 dimethyl 1,2,3,4 tetrahydroisoquinoline

Scheme 6.6 Synthesis of 1,2 dimethyl 1,2,3,4 tetrahydroisoquinoline via iridium catalyzed asymmetric hydrogenation.

A 6,6-dimethyl-6,7-dihydropyrido[l,2-c]quinazolinium salt was obtained from the reaction of 2-(2-aminophenyl)-pyridine and acetone <1997AJC109>. Reaction of 3-methyl-l,2,3,4-tetrahydroisoquinoline-l-acetamides 195 (R = H) with 36% aqueous CH20 gave 1,3,4,6,7,11 b-hcxahydro-2//-pyrirmido[6,1 - ]isoquinolin-2-oncs 153 and their 3-methyl derivatives <1997LA1165>. When the reaction was carried out in the presence of 37% aqueous NaOH, 3-hydroxymethyl derivatives 152 were obtained. Reactions with PhCHO were stereospecific affording only diastereomers 196 (Equation 41). 

The /V -hydroxylamino compounds (404) and (405), obtained from the reaction of tert-butyl acetate with 3,4-dihydroisoquinoline-A-oxide or 5,5-dimethyl-pyrroline-/V-oxide, when boiled in methylene chloride in the presence of triphenylphosphine, carbon tetrachloride and triethylamine, are transformed to (1,2,3,4- tetrahydroisoquinolin-l-ilidene) acetate (406) or (pyrrolidin-2-ilidene) acetate (407) (Scheme 2.181) (645). 

Chemicals and Standard Solutions. Cyclohexanone, cyclohexanol, 1,3,5-trichlorobenzene, 1,2,4-trichlorobenzene, phenol, 4-methylphenol, 4-chloro-phenol, 1,2,3,4-tetrahydroisoquinoline, 1-chlorohexane, 1-chlorododecane, and 1-chlorooctadecane were obtained from Aldrich. Acetone, tetrahydrofuran, ethyl acetate, toluene, dimethyl sulfoxide, and methanol were obtained from J. T. Baker. Distilled-in-glass isooctane, methylene chloride, ethyl ether, and pentane were obtained from Burdick and Jackson. Analytical standard kits from Analabs provided methyl ethyl ketone, isopropyl alcohol, ethanol, methyl isobutyl ketone, tetrachloroethylene, dodecane, dimethylformamide, 1,2-dichlorobenzene, 1-octanol, nitrobenzene, 2,4-dichlorophenol, and 2,5-dichlorophenol. All chemicals obtained from the vendors were of the highest purity available and were used without further purification. High-purity water... 

Ueno et al. 15 reacted l,4-dioxo-l,2,3,4-tetrahydroisoquinoline (406) with carbon disulfide, then methylated to 407, which, with DMAD and potassium carbonate in DMF, gave dimethyl 6,11-dioxo-l-methylthio-3,4, 6,1 l-tetrahydro[l, 4]thiazino[4,3-6]isoquinoline-3,4-dicarboxylate (408). 

The isoquinoline system is conveniently prepared from treatment of o-iodobenzylamines with the enolate ions derived from symmetrical ketones (or ketones with one a-position blocked), aldehydes, or the dimethyl acetal of pyruvaldehyde, to give aminocarbonyl compounds which condensed in situ to give 2- and/or 3-substituted 1,2-dihydroisoquinolines. Catalytic dehydrogenation or borohydride reduction of these products then led to the corresponding isoquinolines or tetrahydroisoquinolines in moderate to high... 

Cyclic amines6 70 including triazoles71 and aziridines,72,73 Good yields of the desired N-substituted 4,4-dimethyl-4-sila-1,2,3,4-tetrahydroisoquinolines are obtained from primary amines and the benzyl bromide derivative. However, due to further reaction, the formation of the non-substituted parent isoquinoline occurs in very low yield. 

Scheme 48) <1998TL4761>. Further examples of this strategy were also reported <2000JOC2684>. A thionium ion-promoted Mannich reaction of the amide 39 upon treatment with dimethyl(methylthio)sulfonium tetrafluoro-borate yields the extended tetrahydroisoquinoline in excellent yield (Equation 105) <2000JOC235>. 

Miyake and co-workers (40) have published a synthesis of ellipticine that features a novel reductive phenylation of nitroarenes (41) (Scheme 4). Nitration of 5,8-dimethyl-l, 2,3,4-tetrahydroisoquinoline (22) gave an inseparable mixture of nitro compounds 23. Treatment of this mixture with iron pentacarbonyl and triflic acid in the presence of benzene gave a 2 1 mixture of amines 24 and 25. Separation of these isomers and diazotization of each with nitrous acid, conversion to the azide, and thermolysis yielded ellipticine (1) and isoellipticine (27) (5,11-dimethyl-10f/-pyrido[3,4- )]carbazole), respectively, following Pd/C dehydrogenation of the initially formed nitrene insertion product (e.g., 26). The overall yield of ellipticine is 9%. 

Dimethoxy-l,2,3,4-tetrahydroisoquinoline hydrochloride Isoquinoline, l,2,3,4-tetrahydro-6,7-dimethoxy-, hydrochloride (8,9) (2328-12-3) (S)-N,N-Dimethy1-N -(l-tert-butoxy-3-methyl-2-butyl)formamidine Methanimidamide, N -[ -[(1,l-d1methy 1 ethoxy)methyl]-2-methylpropyl]-N,N-dimethyl-. (S)- (11) (90482-06-7)... 

Electrochemical oxidation of racemic l,2-dimethyl-7-hydroxy-6-methoxy-1,2,3,4-tetrahydroisoquinoline (22) gives a number of dimers (cf. Vols. 2 and 4) but of the three possible racemic C-8—C-8 dimers (cf. Scheme 2) only one, the racemate corresponding to (23), was obtained.Evidently only molecules of (22)... 

A similar ring-fission occurs when apomorphine is heated with acetic anhydride and hydrochloric acid [71] and when the mono- and dimethyl ethers are heated with benzoyl chloride [72], Another reaction that involves fission of the nitrogen ring is the reaction between diben-zoylapomorphine and cyanogen bromide, which results in [xii] [73]. Other tetrahydroisoquinoline derivatives also suffer ring-fission with this reagent [74-76]. 

SCHEME 9. Electrolysis of l,2-dimethyl-7-hydroxy-6-methoxy-l,2,3,4-tetrahydroisoquinoline... 

The pharmacological properties of N N"-dimethyl-l,2,5,h-tetrahydroisoquinoline 2-carboxamidine hydrochloride,... 

Perhydropyrido[l,2-c][l,3]oxazin-l-ones were prepared in the reaction of the appropriate 2-(2-piperidyl)ethanols and ethyl chloroformate (63AP38) in the presence of sodium ethylate in boiling benzene, or when 2-(2-piperidyl)ethanol was reacted with dimethyl carbonate in the presence of sodium methylate (91X1311). l-Hydroxymethyl-9,10-dimethoxy-l,2,4,6,7,llb-hexahydro-[l,3]oxazino[4,3-fl]isoquinoline-4-oneand 4-thione were prepared from l-[bis(hydroxymethyl)methyl]-6,7-dimethoxy-l,2,3,4-tetrahydroisoquinoline with ethyl chloroformate in the presence of sodium methylate, and thiophosgene in the presence of NEts, respectively... 

If the tetrahydroisoquinoline moiety is connected to a chiral bidentatc complexing group, e.g., 4, then the preformed complex with butyllithium results in rapid removal of the proton from the st-face, forming the lithium complex. In contrast to alkylation, deuteration of this complex by dimethyl sulfoxide-fif6 occurs with retention of configuration (5)11. 

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