1966
The heterocycfic compound 2 is a versatile intermediate for further transformations in the heterocyclic field. For
example, it may be alkylated with methyl iodide affording 8~methoxy-2-methyl-3,4-dihydroisoquinolininm iodide
(3, 71%, mp 185 - 186 °C, recryst, from ethanol) or reduced with sodium borohydride to give 8-methoxy-l,2,3,4-
tct rahydroisoquinofine (4).
. N
I(9
H3CO
H3CO
3
4
Until now, the preparation of 8-methoxy-l,2,3,4-tetrahydroisoquinoline (4) has required lengthy and inefficient
routes [41. The Bischler-Napieralsld type cyclization of N-formyl-2-m-anisylethylamine leads to 6- rather than 8-
met hoxy-3,4-dihydroisoquinoline 15].
Working procedure : 2-m-Anisyl-N-pivaloylethylamine f6] (10 retool) was added to a solution of butyllithium (30
retool) in hexane (20 mL) and diethyl ether (50 mL). After stirring the suspension 2 h at 25 *C, it was treated
with dimethylformamide (60 retool). After 1 h at 25 °C, a concentrated aqueous solution of ammonium chloride
(20 mL) was added. The aldehyde 1 was extracted and purified by elution from silica gel with mixtures of ethyl
acetate and hexane; 55%; mp 91 - 92 °C (recryst. from heptane). [71 - A solution of aldehyde 1 (5 mmol) in
dichloromethane (10 mL) and 10% aqueous hydrochloric acid (20 mL) were vigorously stirred during 24 h at
25 °C. After evaporation of the aqueous phase to dryness, the 8-methoxy-3,4-dihydroisoquinoline hydrochloride
demihydrate (2.HCI.½H.,O) remained as a colorless residue; 79%; mp 183 - 184 °C (dec.; recryst, from
ethanol/diethyl ether)[7l~. - The latter substance (3 mmol) was dissolved in ice-cold methanol (10 mL) which
contained sodium borohydride (3 mmol). After 30 rain at 0 °C, the solvent was evaporated, a 10% aqueous
solution (10 mL) of sodium hydroxide was added and the 8-methoxy-l,2,3,4-tetrahydroisoquinoline (4) was
extracted with dichloromethane (3 × 10 mL). This solvent was subsequently replaced by dicthyl ether (10 mL).
Anhydrous hydrochloric acid caused the precipitation of the 4 • HCI salt; 69%; mp 261 - 262 °C (dec.). [7, B1
Acknowledqement
: The work summarized in the present and the preceding communication was supported by the
Schweizerisehe Nationa]fonds zur P6rderung der wissenschaft]ichen Forschung (grant 20 25'577 88), Berne, by
ZYMA S.A., Nyon, and by the Fondation Herbette, Lausanne.
REFERENCES
[1]
[2]
[3]
Gy. Simig, M. Schlosser, Tetrahedron Lett. 32 (1991), prcceding communication.
M. Schlosser, J. Organomet. Chem. g (1067), 193; Pure AppL Chem. 60 (1988), 1627.
A similar reaction sequence has previously been employed to convert 2-(3,4-dinlethoxyphenyl)-N-(tri-
methylsilyl)ethylamine with 45% yield into 7,8-dimethoxy-3,4-dihydroisoquinoline [C. Lamas, L. Castedo,
D. Dominguez, Tetrahedron Lett. 29 (1988), 3865].
[4]
R.A. Robinson, J. Am. Chem. Soc. 69 (1947), 1944; M. Okamoto, Chem. Phamz. Bull. 15 (1967), 168;
A. Brossi, S. Teitel, Helv. Chim. Acta 53 (1970), 1779; F. Schenker, R.A. Schmidt, T. Williams, A. Brossi,
J. HeterocycL Chem. 8 (1971), 665; R.W. Gray, A.S. Dreiding, Helv. Chim. Acta 63 (1980), 315; M. Rey,
T. Vergnani, A.S. Dreiding, Helv. Chim. Acta 68 (1985), 1828.
[5]
[6]
J.M. Gufiand, C.J. Virden, J. Chem. Soc. 1929, 1793.
Prepared by treating a 1 M solution of 2-m-anisylcthylamine [T. Kametani, K. Kigasawa, M. Hiiragi,
H. Ishimaru, J. Chem. Soc. C 1971, 2632] 15 h at 25 °C with a slight excess of plvaloyl chloride and
pyridine, followed by extraction and recrystallization from heptane; nap 44 - 46 °C [71.
Elementary analyses and full spectroscopic data corroborate the identity and purity of all new compounds.
D.S. Kashdan, J.A. Sehwartz, H. Rapoport, J. Org. Chem. 47 (1982), 2638.
[71
[8]
(Received in France 31 January 1991)
Schlosser
