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Bromine-Lithium exchange on bromo-8-hydroxyquinolines via formation of their sodium salts
Tetrahedron
Letrem, Vol. 36, No. 46, pp. 8415-8418.
1995 Elsevier Science Ltd Printed m Great Britain 0040.4039/95 $9.50+0.00
0040.4039(95)01776-3
Bromine-Lithium Florence
Exchange on Bromo-&hydroxyquinolines Formation of their Sodium Salts.
Mongin, Jean-Marie Fourquez, StCphanie Rault, Vincent Alain Godard, Francois T&court and Guy QuCguiner* Lahoralowe
de Chimie Institut
Fine et HCterocyclique
National
des Sciences
BP 08 7613 I Mont
de I’IRCOF,
Appliquks
Samt Aignan
via
Levacher
associC au CNRS
de Rouen. (France)
Abstract: A short and versatile method 1s reported for the preparation of X-hydroxyquinoline derivatives by reaction of n-hutylhthium with 5,7-dibromo-8.hydroxyqulnoline 2 and 7-bromo-Shydroxyqumoline 1 as their so&urn salts. Thus. brornme-lithium exchange reaction on compound 2. highly regioselecrlve. gave after addition of various electrophiles, kubstituted 7-bromo-8hydroxyquinolines 4a-j in moderate to good yields. The same procedure was also applicable to 7. bromo-Ghydroxyquinoline 1 which led to 7.substituted X-hydroxyqumolmes 3a-b.
As part of a project which aimed at obtaining oxinr derivatives. we have been interested in the development of new methods to obtain 8-hydroxyquinoline derivatives differently substituted on the phenyl ring. Oxine and its derivatives have in the past received considerable attention for their biological propertiest and have been used extensively in the field of metallurgy and analytical chemistry as selective metal extracting agents and corrosion inhibitors.* Nevertheless, a survey of the literature revealed that few efficient and general methods are available to have access to oxine derivatives. The classical methods are cyclization reactions based on substituted benzene derivatives.3 These methods present limited synthetic use because of the difficulty in preparing polysubstituted benzene derivatives. On the other hand, Friedel-Crafts reactions of 8-hydroxyquinoline led to a mixture of 5and -/-substituted S-hydroxyquinolines in poor yields4 Moreover, these methods lack versatility and are carried out under drastic conditions. More recently, our group studied a new method of fonctionalization of oxine using the directed m-rho metalation of N,N-dimethylcarbamates of 8-hydroxyquinoline.s
Br
Br 1) n-Buli
/ THF
Br
Br
or Et20i
Br
Scheme
1
In connection with this work, our interest has been focused on the bromine-lithium exchange reaction of the readily available 7-bromo-8-hydroxyquinoline l6 and 5,7-dibromo-%hydroxyquinoline 2.7 In a first attempt to achieve bromine-lithium exchange reaction, 5.7.dibromo-8-methoxyquinoline8 proved inconvenient for this purpose, since in addition to the expected exchange reaction, the 8-methoxyquinoline derivative undergoes nucleophilic attack’ by n-butyllithium (Scheme 1).
8416
On further consideration, we decided to investigate the bromine-lithium exchange reaction on the salts of the oxine derivatives 1 and 2. Indeed, according to their higher electron density, the salts of the oxine derivatives 1 and 2 were thought to be less sensitive to nucleophilic addition than their methoxy derivatives. With this aim in view, the sodium salt of compound 1 was formed at room temperature prior to adding nbutyllithium at -78°C (Scheme 2). Quenching the reaction medium with such electrophiles as Me3SiCl or p MeO-PhCHO (-78°C 1h; -30°C 2h; 0°C 2h), afforded 7-substituted ghydroxyquinolines 3a-b’O in moderate yields (Table 1) along with S-hydroxyquinoline. It must be pointed out that undesired products resulting from the nucleophilic attack of n-butyllithium at C-2 position could not be detected. This approach has the advantage of not only suppressing addition reaction of n-butyllithium but also avoiding a supplementary step of deprotection to have access to the desired 8-hydroxyquinolines.
Table 1: Bromine-lithium hydroxyquinolme
OH
1
OH
exchange
on 7-bromo-8-
3a-b Me$iCI
Scheme 2: a) NaH (1.5 eq) / THF / Rt / 2 h / N, : b) n-BuLI (1.1 eq) / -78°C / 1 h / N2 ; c) Electrophile (2 eq)
p MeO-PhCHO
MesSi p MeO-PhCH(OH)
3a: 63% 3b: 57%
With this first promising result in hand, we turned our interest towards the bromine-lithium exchange reaction of 5,7-dibromo-8-hydroxyquinoline 2. Thus. the sodium salt of 5,7-dibromo-8-hydroxyquinoline 2 was formed prior to adding I eq of n-butyllithium at -78°C. Addition of EtOD afforded the deuterated compound 4a in 90% yield together with compound 1 in 10% yield (Scheme 3). The formation of compounds 4a and 1 as the sole products of the reaction clearly indicates that bromine-lithium exchange occured regioselectively at the C-5 position.
Scheme
3 Br 1) NaH (1.2 eq) i 20’C 2) n-BULI (1.1 eq) / -78°C
l@] 5 Br&RzD Yie,d = 90% 1: R=H Yield = 10%
It should be noted that the sodium salt of 7-bromo-8-hydroxyquinoline 1 proved to be less reactive than the sodium salt of 5.7.dibromo-8.hydroxyquinoline 2, since it reacted with n-butyllithium at -78°C in 1 hour whereas under the same conditions the sodium salt of compound 2 reacted in 15 mn. The lower reactivity of compound 1 towards bromine-lithium exchange reaction is in agreement with the high degree of regioselectivity observed at C-5 position with 5,7-dibromo-8-hydroxyquinoline 2.
8417
To confirm the synthetic interest of this regioselective bromine-lithium exchange reaction, we used a large range of electrophiles to quench the reaction medium. Thus, 7-bromo-8-hydroxy-5-substituted quinolines 4a-j’ ’ were obtained in moderate to good yields (table 2). In conclusion, it seems that the regioselective brominelithium exchange reaction of oxine derivative 2 opens up an efficient and versatile way to 5substituted 7bromo-8-hydroxyquinolines. This method found applications in the synthesis of various heteroaromatics.12
Table
2: Bromine-llthlum
exchange
on 5.7.dibromo-8-hydroxyquinoline
Synthesis of S-substituted 7-bromo-%hydroxyquinolines 4a-4j; general procedure: To a suspension of sodium hydride (as an 8010 suspension in oil , 356 mg, 11.9 mmol) in THF (80 mL), was added under N2, 5,7-dibromo-8-hydroxyquinoline (3 g, 9.9 mmol) over a period of 10 min. After 2 h stirring at room temperature, the resulting green solution was precooled at -78’C before adding a solution of n-butyllithium in hexane (4.4 mL, 10.9 mmol, 2.5 M) as such rate to keep the solution at -78°C. During this period the solution turned pale brown from green. The solution was stirred for 15 min at -78°C after which time boron trifluoride etherate (19.8 mmol) was added when oxirane was used as electrophile. The appropriate electrophile (23.8 mmol for chlorotrimethylsilane and 1 I .9 mmol for the others) in THF (10 mL) was added dropwise at -78°C and the obtained solution was stirred at this temperature for a further 2 h. The solution was hydrolyzed at -78°C with 15 mL of 2 M HCl in THF and was allowed to reach room temperature. After treatment with 1 M aq NaHC03 (50 mL) and phase separation. the aqueous phase was extracted 3 times with CH2Cl2 (30 mL). The combined organic phases were dried (Na2S04) and the solvents were evaporated under vacuum to afford the crude product. Compounds 4d. 4e and 4i were purified by recrystallization (4d and 4e from toluene; 4i from hexane). Compound 4c was obtained pure by washings with ether (15 mL). Compounds 4b, 4h, 4f, 4g and 4j were purified by flash chromatography on silica gel (compounds 4b, 4h: CH2C12 then EtOAc as eluent; compounds 4f. 4g, 4j: CH2Cl2 as eluent). Acknowledgment: this work.
We thank la Quinoleine
(Oissel plant; France) and Schering AG for financial
REFERENCES I.
AND
support of
NOTES
Albert, A.; Rubbo, S. D.; Goldacre, R. J.: Balfour, B. G. Brit. J. Expfl. Pnthol. 1947, 28, 69-87. Gershon, H.; Parmegiani, P. Appl. Micmbiol. 1963, II, 62-65. Shchukina, M. N.; Savitskaya, N.V. Zh. Obshch. Kim. 1952, 22, 1218-1224. Trotz, S. I.; Pitts, J. J. Kirk-Othmer Encycl. Chem. Technal., Wiley-Interscience. New York. 3 rd edn. 1981. 13, 223. Gershon, H.; Clarke, D.D.; Gershon. M. Monatsh. Chem. 1994. 125 (I), 51-59.
8418
2.
3. 4. 5. 6. 7. 8.
9. 10.
11.
12.
Corsini, A.; Cassidi, R.M. Talanta, 1979, 26, 297-301. Demura, Y.; Hirakawa, K.; Murase, I. Bull. C&m. %c. Jpn. 1982,55, 2863-2865. Uhlemann, E.; Weber, W. U. Z. anorg. allg. Chem. 1984, 510, 79-87. Uhlemann, E.; Schilde, U. 2. anorg. allg. Chew. 1985, 524, 193-200. Friedrich, A.; Uhlemann, E.; Schilde, U. Z. anorg. allg. Chem. 1986, 534, 199-205. Song, K.; Yang, J.; Liu, X. Chin. J. Chem. 19% 12, 19-25. Sagawa, T.; Imura, H.; Ohashi, K. Proc. Symp. Solvent Extr. 1993,73 (Chem. Abstr. 121, 239339~). Kolobielski, M.; J. Heterocycl. Chem. 1966, 3, 275277. Uhlemann, E.; Mickler, W.: Ludwig, E. J. prukt. Chem. 1981, 323, 3, 521-524. QuQuiner, G.; Marsais, F.; Snieckus, V. and Epsztajn, J. Advances in Heterocyclic Chemistry 1991, 52, 186-304 and references cited therein. Pearson, D.E.; Wysong, R. D.; Breder, C.V. J. Org. Chem. 1967,32, 2358-2360. Gershon, H.; McNeil, M. W.; Schulman, S.G. J. Org. Chem. 1971, 36, 1616-1619. DOLL H. J. M. Chimie-Actualife’s 1971, 22 Sept. Dou, H. J. M.; Hassanaly, P.; Metzer, J. J. Heterocycl. Chem. 1977, 323-323. Trkourt, F.; Mallet, M.; Mongin, F.; QuCguiner, G. Synthesis, in press. It is already mentioned in the literature that quinolines are sensitive to nucleophilic attack with organolithium and organomagnesium reagents. For further details see ref.5. lH NMR data (6, ppm; J, Hz): Compound 3a (CDC13 at 60 MHzj 6 0.40 (s, 9H), 7.60-7.20 (m, 3H), 8.10 (dd, IH, J = X.2-1.4), 8.75 (dd, lH, J = 4.2-1.4). compound 3b (DMSO-d6 at 400 MHz) 6 3.68 (s, 3H), 6.24 (s. IH), 6.83 (d, 2 H, J = 8.8). 7.32 (d, 2H, J = 8.8). 7.38 (d, IH, / = 8.5), 7.50 (dd, 1H. .I = 8.2.4.2), 7.66 (d, lH, .I = 8.5), 8.27 (dd, 1H. / = 8.2-1.4), 8.82 (dd, IH, J = 4.2-1.4). ‘H NMR data (6, ppm; J, Hz): compound 4a (DMSO-d6 at 200 MHz) 6 7.61 (dd,lH, J = 8.4-4.2), 7.67 (s, IH), 8.38 (dd, IH, / = 8.4-l.S), 8.89 (dd, lH, J = 4.2-1.5). Compound 4b (DMSO-d6 at 200 MHz) 6 6.24 (s, lH), 7.31 (m, 5H), 7.46 (dd. lH, J = 8.7.4.2), 7.71 (s, IH), 8.48 (dd, lH, J = 8.7.l.4), 8.82 (dd, lH, J = 4.2-1.4). Compound 4c (DMSO-d6 at 200 MHz) 6 7.84 (dd, lH, J = 8.6-4.2), 8.40 (s. 1H). 8.96 (dd, IH, J = 4.2.l.O), 9.56 (dd, IH. J = 8.6-l.O), 10.07 (s, 1H). Compound 4d (DMSO-d6 at 200 MHz) 6 7.73 (dd, lH, J = 8.5.4.2), 8.22 (s, lH), 8.30 (dd, lH, J = 8.5-1.4). 8.89 (dd. 1H. J = 4.2-1.4). Compound 4e (CDC13 at 200 MHz) 6 7.73 (dd, lH, J = 8.5 4.2), 7.85 (s, IH). 8.44 (dd, lH, J = 8.5-1.5). 8.96 (dd, lH, J = 4.2-1.5). Compound 4f (CDC13 at 200 MHz) 6 0.45 (s. 9H), 7.50 (dd, 1H. J = 8.5.4.2), 7.75 (s, 1H). 8.39 (dd, lH, J = 8.5-l.4), 8.80 (dd, lH, J = 4.2-1.4). Compound 4g (CDC13 at 200 MHz) 6 2.58 (s, 3H), 7.46 (s, lH), 7.50 (dd, lH, J = 8.5-4.2). 8.26 (dd. IH. J = 8.5-1.5). 8.80 (dd. IH, J = 4.2-1.5). Compound 4b (DMSO-d6 at 200 MHz) 6 3.09 (t, 2H. J = 6.4), 3.70 (t, 2H, J = 6.4), 7.52 (s, IH), 7.55 (dd, lH, / = 8.63.8), 8.50 (dd, IH. J = 8.6-l.4), 8.89 (dd, IH, J = 3.8-1.4). Compound 4i (CDC13 at 60 MHz) 8 1.85-0.65 (m, 13H), 2.85 (t. 2H. J = 7.5), 7.50-7.20 (m, 2H), 8.25 (dd, 1H. J = 8.5-1.5), 8.75 (dd , 1H. J = 3.0-1.5). Compound 4j (DMSC-d6 at 60 MHz) S 3.65 (s, 3H), 6.20 (s, IH), 6.85 (d. ?H, / = 8.51, 7.65-7.10 [m. SH), 8.25 (dd, lH. J = 851.5). 8.80 (dd, lH, J = 4.0-1.5). Trkcourt. F.; Mongin, F.; Mallet, M.; QuCguiner. G. J. Heterocycl. Chem., in press. TrCcourt, F.; Mongin, F.: Mallet. M.: Qukguiner. G. Syr&z. Commun., in press.
(Received
in France
21 June
1995; accepted
I5 September
1995)
Letrem, Vol. 36, No. 46, pp. 8415-8418.
1995 Elsevier Science Ltd Printed m Great Britain 0040.4039/95 $9.50+0.00
0040.4039(95)01776-3
Bromine-Lithium Florence
Exchange on Bromo-&hydroxyquinolines Formation of their Sodium Salts.
Mongin, Jean-Marie Fourquez, StCphanie Rault, Vincent Alain Godard, Francois T&court and Guy QuCguiner* Lahoralowe
de Chimie Institut
Fine et HCterocyclique
National
des Sciences
BP 08 7613 I Mont
de I’IRCOF,
Appliquks
Samt Aignan
via
Levacher
associC au CNRS
de Rouen. (France)
Abstract: A short and versatile method 1s reported for the preparation of X-hydroxyquinoline derivatives by reaction of n-hutylhthium with 5,7-dibromo-8.hydroxyqulnoline 2 and 7-bromo-Shydroxyqumoline 1 as their so&urn salts. Thus. brornme-lithium exchange reaction on compound 2. highly regioselecrlve. gave after addition of various electrophiles, kubstituted 7-bromo-8hydroxyquinolines 4a-j in moderate to good yields. The same procedure was also applicable to 7. bromo-Ghydroxyquinoline 1 which led to 7.substituted X-hydroxyqumolmes 3a-b.
As part of a project which aimed at obtaining oxinr derivatives. we have been interested in the development of new methods to obtain 8-hydroxyquinoline derivatives differently substituted on the phenyl ring. Oxine and its derivatives have in the past received considerable attention for their biological propertiest and have been used extensively in the field of metallurgy and analytical chemistry as selective metal extracting agents and corrosion inhibitors.* Nevertheless, a survey of the literature revealed that few efficient and general methods are available to have access to oxine derivatives. The classical methods are cyclization reactions based on substituted benzene derivatives.3 These methods present limited synthetic use because of the difficulty in preparing polysubstituted benzene derivatives. On the other hand, Friedel-Crafts reactions of 8-hydroxyquinoline led to a mixture of 5and -/-substituted S-hydroxyquinolines in poor yields4 Moreover, these methods lack versatility and are carried out under drastic conditions. More recently, our group studied a new method of fonctionalization of oxine using the directed m-rho metalation of N,N-dimethylcarbamates of 8-hydroxyquinoline.s
Br
Br 1) n-Buli
/ THF
Br
Br
or Et20i
Br
Scheme
1
In connection with this work, our interest has been focused on the bromine-lithium exchange reaction of the readily available 7-bromo-8-hydroxyquinoline l6 and 5,7-dibromo-%hydroxyquinoline 2.7 In a first attempt to achieve bromine-lithium exchange reaction, 5.7.dibromo-8-methoxyquinoline8 proved inconvenient for this purpose, since in addition to the expected exchange reaction, the 8-methoxyquinoline derivative undergoes nucleophilic attack’ by n-butyllithium (Scheme 1).
8416
On further consideration, we decided to investigate the bromine-lithium exchange reaction on the salts of the oxine derivatives 1 and 2. Indeed, according to their higher electron density, the salts of the oxine derivatives 1 and 2 were thought to be less sensitive to nucleophilic addition than their methoxy derivatives. With this aim in view, the sodium salt of compound 1 was formed at room temperature prior to adding nbutyllithium at -78°C (Scheme 2). Quenching the reaction medium with such electrophiles as Me3SiCl or p MeO-PhCHO (-78°C 1h; -30°C 2h; 0°C 2h), afforded 7-substituted ghydroxyquinolines 3a-b’O in moderate yields (Table 1) along with S-hydroxyquinoline. It must be pointed out that undesired products resulting from the nucleophilic attack of n-butyllithium at C-2 position could not be detected. This approach has the advantage of not only suppressing addition reaction of n-butyllithium but also avoiding a supplementary step of deprotection to have access to the desired 8-hydroxyquinolines.
Table 1: Bromine-lithium hydroxyquinolme
OH
1
OH
exchange
on 7-bromo-8-
3a-b Me$iCI
Scheme 2: a) NaH (1.5 eq) / THF / Rt / 2 h / N, : b) n-BuLI (1.1 eq) / -78°C / 1 h / N2 ; c) Electrophile (2 eq)
p MeO-PhCHO
MesSi p MeO-PhCH(OH)
3a: 63% 3b: 57%
With this first promising result in hand, we turned our interest towards the bromine-lithium exchange reaction of 5,7-dibromo-8-hydroxyquinoline 2. Thus. the sodium salt of 5,7-dibromo-8-hydroxyquinoline 2 was formed prior to adding I eq of n-butyllithium at -78°C. Addition of EtOD afforded the deuterated compound 4a in 90% yield together with compound 1 in 10% yield (Scheme 3). The formation of compounds 4a and 1 as the sole products of the reaction clearly indicates that bromine-lithium exchange occured regioselectively at the C-5 position.
Scheme
3 Br 1) NaH (1.2 eq) i 20’C 2) n-BULI (1.1 eq) / -78°C
l@] 5 Br&RzD Yie,d = 90% 1: R=H Yield = 10%
It should be noted that the sodium salt of 7-bromo-8-hydroxyquinoline 1 proved to be less reactive than the sodium salt of 5.7.dibromo-8.hydroxyquinoline 2, since it reacted with n-butyllithium at -78°C in 1 hour whereas under the same conditions the sodium salt of compound 2 reacted in 15 mn. The lower reactivity of compound 1 towards bromine-lithium exchange reaction is in agreement with the high degree of regioselectivity observed at C-5 position with 5,7-dibromo-8-hydroxyquinoline 2.
8417
To confirm the synthetic interest of this regioselective bromine-lithium exchange reaction, we used a large range of electrophiles to quench the reaction medium. Thus, 7-bromo-8-hydroxy-5-substituted quinolines 4a-j’ ’ were obtained in moderate to good yields (table 2). In conclusion, it seems that the regioselective brominelithium exchange reaction of oxine derivative 2 opens up an efficient and versatile way to 5substituted 7bromo-8-hydroxyquinolines. This method found applications in the synthesis of various heteroaromatics.12
Table
2: Bromine-llthlum
exchange
on 5.7.dibromo-8-hydroxyquinoline
Synthesis of S-substituted 7-bromo-%hydroxyquinolines 4a-4j; general procedure: To a suspension of sodium hydride (as an 8010 suspension in oil , 356 mg, 11.9 mmol) in THF (80 mL), was added under N2, 5,7-dibromo-8-hydroxyquinoline (3 g, 9.9 mmol) over a period of 10 min. After 2 h stirring at room temperature, the resulting green solution was precooled at -78’C before adding a solution of n-butyllithium in hexane (4.4 mL, 10.9 mmol, 2.5 M) as such rate to keep the solution at -78°C. During this period the solution turned pale brown from green. The solution was stirred for 15 min at -78°C after which time boron trifluoride etherate (19.8 mmol) was added when oxirane was used as electrophile. The appropriate electrophile (23.8 mmol for chlorotrimethylsilane and 1 I .9 mmol for the others) in THF (10 mL) was added dropwise at -78°C and the obtained solution was stirred at this temperature for a further 2 h. The solution was hydrolyzed at -78°C with 15 mL of 2 M HCl in THF and was allowed to reach room temperature. After treatment with 1 M aq NaHC03 (50 mL) and phase separation. the aqueous phase was extracted 3 times with CH2Cl2 (30 mL). The combined organic phases were dried (Na2S04) and the solvents were evaporated under vacuum to afford the crude product. Compounds 4d. 4e and 4i were purified by recrystallization (4d and 4e from toluene; 4i from hexane). Compound 4c was obtained pure by washings with ether (15 mL). Compounds 4b, 4h, 4f, 4g and 4j were purified by flash chromatography on silica gel (compounds 4b, 4h: CH2C12 then EtOAc as eluent; compounds 4f. 4g, 4j: CH2Cl2 as eluent). Acknowledgment: this work.
We thank la Quinoleine
(Oissel plant; France) and Schering AG for financial
REFERENCES I.
AND
support of
NOTES
Albert, A.; Rubbo, S. D.; Goldacre, R. J.: Balfour, B. G. Brit. J. Expfl. Pnthol. 1947, 28, 69-87. Gershon, H.; Parmegiani, P. Appl. Micmbiol. 1963, II, 62-65. Shchukina, M. N.; Savitskaya, N.V. Zh. Obshch. Kim. 1952, 22, 1218-1224. Trotz, S. I.; Pitts, J. J. Kirk-Othmer Encycl. Chem. Technal., Wiley-Interscience. New York. 3 rd edn. 1981. 13, 223. Gershon, H.; Clarke, D.D.; Gershon. M. Monatsh. Chem. 1994. 125 (I), 51-59.
8418
2.
3. 4. 5. 6. 7. 8.
9. 10.
11.
12.
Corsini, A.; Cassidi, R.M. Talanta, 1979, 26, 297-301. Demura, Y.; Hirakawa, K.; Murase, I. Bull. C&m. %c. Jpn. 1982,55, 2863-2865. Uhlemann, E.; Weber, W. U. Z. anorg. allg. Chem. 1984, 510, 79-87. Uhlemann, E.; Schilde, U. 2. anorg. allg. Chew. 1985, 524, 193-200. Friedrich, A.; Uhlemann, E.; Schilde, U. Z. anorg. allg. Chem. 1986, 534, 199-205. Song, K.; Yang, J.; Liu, X. Chin. J. Chem. 19% 12, 19-25. Sagawa, T.; Imura, H.; Ohashi, K. Proc. Symp. Solvent Extr. 1993,73 (Chem. Abstr. 121, 239339~). Kolobielski, M.; J. Heterocycl. Chem. 1966, 3, 275277. Uhlemann, E.; Mickler, W.: Ludwig, E. J. prukt. Chem. 1981, 323, 3, 521-524. QuQuiner, G.; Marsais, F.; Snieckus, V. and Epsztajn, J. Advances in Heterocyclic Chemistry 1991, 52, 186-304 and references cited therein. Pearson, D.E.; Wysong, R. D.; Breder, C.V. J. Org. Chem. 1967,32, 2358-2360. Gershon, H.; McNeil, M. W.; Schulman, S.G. J. Org. Chem. 1971, 36, 1616-1619. DOLL H. J. M. Chimie-Actualife’s 1971, 22 Sept. Dou, H. J. M.; Hassanaly, P.; Metzer, J. J. Heterocycl. Chem. 1977, 323-323. Trkourt, F.; Mallet, M.; Mongin, F.; QuCguiner, G. Synthesis, in press. It is already mentioned in the literature that quinolines are sensitive to nucleophilic attack with organolithium and organomagnesium reagents. For further details see ref.5. lH NMR data (6, ppm; J, Hz): Compound 3a (CDC13 at 60 MHzj 6 0.40 (s, 9H), 7.60-7.20 (m, 3H), 8.10 (dd, IH, J = X.2-1.4), 8.75 (dd, lH, J = 4.2-1.4). compound 3b (DMSO-d6 at 400 MHz) 6 3.68 (s, 3H), 6.24 (s. IH), 6.83 (d, 2 H, J = 8.8). 7.32 (d, 2H, J = 8.8). 7.38 (d, IH, / = 8.5), 7.50 (dd, 1H. .I = 8.2.4.2), 7.66 (d, lH, .I = 8.5), 8.27 (dd, 1H. / = 8.2-1.4), 8.82 (dd, IH, J = 4.2-1.4). ‘H NMR data (6, ppm; J, Hz): compound 4a (DMSO-d6 at 200 MHz) 6 7.61 (dd,lH, J = 8.4-4.2), 7.67 (s, IH), 8.38 (dd, IH, / = 8.4-l.S), 8.89 (dd, lH, J = 4.2-1.5). Compound 4b (DMSO-d6 at 200 MHz) 6 6.24 (s, lH), 7.31 (m, 5H), 7.46 (dd. lH, J = 8.7.4.2), 7.71 (s, IH), 8.48 (dd, lH, J = 8.7.l.4), 8.82 (dd, lH, J = 4.2-1.4). Compound 4c (DMSO-d6 at 200 MHz) 6 7.84 (dd, lH, J = 8.6-4.2), 8.40 (s. 1H). 8.96 (dd, IH, J = 4.2.l.O), 9.56 (dd, IH. J = 8.6-l.O), 10.07 (s, 1H). Compound 4d (DMSO-d6 at 200 MHz) 6 7.73 (dd, lH, J = 8.5.4.2), 8.22 (s, lH), 8.30 (dd, lH, J = 8.5-1.4). 8.89 (dd. 1H. J = 4.2-1.4). Compound 4e (CDC13 at 200 MHz) 6 7.73 (dd, lH, J = 8.5 4.2), 7.85 (s, IH). 8.44 (dd, lH, J = 8.5-1.5). 8.96 (dd, lH, J = 4.2-1.5). Compound 4f (CDC13 at 200 MHz) 6 0.45 (s. 9H), 7.50 (dd, 1H. J = 8.5.4.2), 7.75 (s, 1H). 8.39 (dd, lH, J = 8.5-l.4), 8.80 (dd, lH, J = 4.2-1.4). Compound 4g (CDC13 at 200 MHz) 6 2.58 (s, 3H), 7.46 (s, lH), 7.50 (dd, lH, J = 8.5-4.2). 8.26 (dd. IH. J = 8.5-1.5). 8.80 (dd. IH, J = 4.2-1.5). Compound 4b (DMSO-d6 at 200 MHz) 6 3.09 (t, 2H. J = 6.4), 3.70 (t, 2H, J = 6.4), 7.52 (s, IH), 7.55 (dd, lH, / = 8.63.8), 8.50 (dd, IH. J = 8.6-l.4), 8.89 (dd, IH, J = 3.8-1.4). Compound 4i (CDC13 at 60 MHz) 8 1.85-0.65 (m, 13H), 2.85 (t. 2H. J = 7.5), 7.50-7.20 (m, 2H), 8.25 (dd, 1H. J = 8.5-1.5), 8.75 (dd , 1H. J = 3.0-1.5). Compound 4j (DMSC-d6 at 60 MHz) S 3.65 (s, 3H), 6.20 (s, IH), 6.85 (d. ?H, / = 8.51, 7.65-7.10 [m. SH), 8.25 (dd, lH. J = 851.5). 8.80 (dd, lH, J = 4.0-1.5). Trkcourt. F.; Mongin, F.; Mallet, M.; QuCguiner. G. J. Heterocycl. Chem., in press. TrCcourt, F.; Mongin, F.: Mallet. M.: Qukguiner. G. Syr&z. Commun., in press.
(Received
in France
21 June
1995; accepted
I5 September
1995)