![Soluble Expression of (+)-γ-Lactamase in Bacillus subtilis for ...biocat.jiangnan.edu.cn/__local/7/B9/F1/D4E9D1AA92C53F...[3]. While (−)-γ-lactam can be applied in the synthesis](https://static.fdocument.org/doc/165x107/60d7f4c9fffa135fc614cee2/soluble-expression-of-lactamase-in-bacillus-subtilis-for-3-while.jpg)
7-(γ-Diethylaminopropylamino)-isoquinoline 1
1
1944 RICHARD A. ROHINSON [CONTRIBUTION FROM THE LABORATO~IES OF G. D. SEARLE AND COMPANY] 7-(~-Diethylaminopropylamino)-isoquinoline BY RICHARD A. ROBINSON In continuation of the study of basically alky- lated aminois~quinolines~~~ we have prepared 7- (y-diethylaminopropy1amino)-isoquinoline. In the second paper of this series it was shown that 5- ( y -diethylaminoprop ylamino) -isoquinoline could be prepared by the application of the Bucherer reaction to 5-hydroxyisoquinoline. The 7-hy- droxyisoquinoline, under similar conditions, was found to react with even greater ease than the 5 4 (1) Presented before the Organic Section of the American Chemi- cal Society, Sept., 1946. 5-isomer, yielding 65% of 7-(y-diethylamino- propylamino) -isoquinoline. With ammonium sulfite practically quantitative yields of 7-amino- isoquinoline3 were obtained. Experimental 7- (7 -Diethylaminopropylamino) -isoquinoline .-Four- teen and five-tenths grams of 7-hydroxyisoquinoline, 45 g. of ydiethylaminopropylamine, 100 ml. of water and 12.8 g. of sulfur dioxide were refluxed under a pressure of 3 in. for thirty-six hours. The product was isolated by ether extraction and purified by distillation a t 3 mm. The dihydrochloride, yellow needles of m. p. 145', was purified by recrystallization from isopropanol. By desiccation a t lOO", 1 mm., for twelve hours a weight loss of 4.54% occurred. The analysis is reported on a dry basis. Anal. Calcd. for C I B H ~ ~ C I ~ N ~ : C, 58.18; H, 7.63; C1.21.47. Found: C, 58.1; H,8.17; C1, 21.62. Summary (2) This work was undertaken in cooperation with the Survey of Antimalarial Drugs of the National Research Council. The results of antimalarial screening tests on the compounds here reported will be found in "Antimalarial Drugs 1941-1845," Edwards Brothers, Ann Arbor. :\Iichigan, 1946. The preparation of 7-(y-diethylaminopropyl- amino)-isoquinoline is described. CHICAGO, ILLINOIS 13) Rohinson. THIS JCURNAI., paper 2. 69, 19-12 (1947). RECEIVED FEBRUARY 3, 1947 [CONTRIBUTION FROM ?HE LABORATORIES OF G. D. SEARLE AND COMPASY.]. 8- (7-Diethylaminopropylamino) 4soquinoline BY RICHARD A. ROBINSON In preceding papers2s3 we have described the synthesis of 5- and 7-(y-diethylaminopropyl- amino)-isoquinoline by application of the Bu- cherer reaction to 5- and 7-hydroxyisoquinoline. In view of the difficulties encountered with other methods tried for this type of sub~titution~~ the Bucherer reaction seemed to present the most hopeful means for introducing a dialkylamino- alkylamino group at position 8. Although the 8-hydroxyisoquinoline required for this reaction had never been described a suggestion for a pos- sible method of preparation was found in ClausJ4 work on isoquinolinesulfonic acids. He obtained by sulfonation of isoquinoline at 115" two iso- quinolinesulfonic acids which he designated as Acids I and 11. Acid I, the chief product, has now been established as isoquinoline-5-sulfonic (1) Presented before the Organic Section of the American Chemical Society. Sept., ;946. (2) This work was undertaken in cooperation with the Survey of Antimalarial Drugs of the National Research Council. The results of antimalarial screening tests on the compounds here reported will he found in "Antimalarial Drugs 1941-1945," Edwards Brothers, Ann Arbor, Michigan, 1846. (3) (a) Robinson, THIS JOURNAL, paper 2, 69, 1942 (1947): (b) ilaper 3. 69, 1944 (1947). (1) Claus and Raps, J. 3rakl. Chem., (2) 45, 211 (1892); Claus and Seeleman. ihid . 52, 1 (1895). acid.j By sulfonation at 300' acid I1 was the chief product. This acid on caustic fusion yielded a hydroxyisoquinoline of m. p. 184" whose struc- ture was not known. We repeated the prepara- tion of this hydroxyisoquinoline with the hope that it would be the 8-hydroxyisoquinoline. The sulfonation of isoquinoline (A), carried out at 300" as suggested by Claus, produced about 35% of isoquinoline-5-sulfonic acid which could be sepa- rated by means of a difficultly soluble calcium salt. The residue of soluble calcium salts which was evidently a mixture could not be resolved into its pure components. By converting this mix- ture to the sodium salts and fusing with 60y0 so- dium hydroxide a new hydroxyisoquinoline was obtained in an over-all yield of 15%. This new hydroxyisoquinoline melted at 213'; it was en- tirely pure and showed no tendency to be unstable as suggested by Claus. It was different from the known 5- and 7-hydroxyisoquinoline and from 6- hydroxyisoquinoline which was prepared by de- methylation of 6-metho~yisoquinoline.~ It re- acted with ammonium sulfite yielding 85% of an (5) Tyson, THIS JOURNAL, 61, 183 (1939); Andersag, .Wed. Chem. Abhandl. a. mcd. chcm., 2, 377 (1934); Claus and Gutzeit, J. prnkl Chem., [Z] 52, 9 (1895). (6) Robinson, ibid., paper 1. 69, 1939 (1947).
Transcript of 7-(γ-Diethylaminopropylamino)-isoquinoline 1
1944 RICHARD A . ROHINSON
[CONTRIBUTION FROM THE LABORATO~IES OF G. D. SEARLE AND COMPANY]
7-(~-Diethylaminopropylamino)-isoquinoline BY RICHARD A. ROBINSON
In continuation of the study of basically alky- lated aminois~quinolines~~~ we have prepared 7- (y-diethylaminopropy1amino)-isoquinoline. In the second paper of this series i t was shown that 5- ( y -diethylaminoprop ylamino) -isoquinoline could be prepared by the application of the Bucherer reaction to 5-hydroxyisoquinoline. The 7-hy- droxyisoquinoline, under similar conditions, was found to react with even greater ease than the
5 4
(1) Presented before the Organic Section of the American Chemi- cal Society, Sept. , 1946.
5-isomer, yielding 65% of 7-(y-diethylamino- propylamino) -isoquinoline. With ammonium sulfite practically quantitative yields of 7-amino- isoquinoline3 were obtained.
Experimental 7- (7 -Diethylaminopropylamino) -isoquinoline .-Four-
teen and five-tenths grams of 7-hydroxyisoquinoline, 45 g. of ydiethylaminopropylamine, 100 ml. of water and 12.8 g. of sulfur dioxide were refluxed under a pressure of 3 in. for thirty-six hours. The product was isolated by ether extraction and purified by distillation a t 3 mm. The dihydrochloride, yellow needles of m. p. 145', was purified by recrystallization from isopropanol. By desiccation a t lOO", 1 mm., for twelve hours a weight loss of 4.54% occurred. The analysis is reported on a dry basis.
Anal. Calcd. for C I B H ~ ~ C I ~ N ~ : C, 58.18; H, 7.63; C1.21.47. Found: C, 58.1; H,8.17; C1, 21.62.
Summary (2) This work was undertaken in cooperation with the Survey of Antimalarial Drugs of t h e National Research Council. T h e results of antimalarial screening tests on the compounds here reported will be found in "Antimalarial Drugs 1941-1845," Edwards Brothers, Ann Arbor. :\Iichigan, 1946.
The preparation of 7-(y-diethylaminopropyl- amino)-isoquinoline is described. CHICAGO, ILLINOIS 13) Rohinson. THIS JCURNAI., paper 2. 69, 19-12 (1947) . RECEIVED FEBRUARY 3 , 1947
[CONTRIBUTION FROM ?HE LABORATORIES OF G. D. SEARLE AND COMPASY.].
8- (7-Diethylaminopropylamino) 4soquinoline BY RICHARD A. ROBINSON
In preceding papers2s3 we have described the synthesis of 5- and 7-(y-diethylaminopropyl- amino)-isoquinoline by application of the Bu- cherer reaction to 5- and 7-hydroxyisoquinoline. In view of the difficulties encountered with other methods tried for this type of s u b ~ t i t u t i o n ~ ~ the Bucherer reaction seemed to present the most hopeful means for introducing a dialkylamino- alkylamino group a t position 8. Although the 8-hydroxyisoquinoline required for this reaction had never been described a suggestion for a pos- sible method of preparation was found in ClausJ4 work on isoquinolinesulfonic acids. He obtained by sulfonation of isoquinoline a t 115" two iso- quinolinesulfonic acids which he designated as Acids I and 11. Acid I, the chief product, has now been established as isoquinoline-5-sulfonic
(1) Presented before the Organic Section of t h e American Chemical Society. Sept., ;946.
(2) This work was undertaken in cooperation with the Survey of Antimalarial Drugs of t h e National Research Council. T h e results of antimalarial screening tests on the compounds here reported will he found in "Antimalarial Drugs 1941-1945," Edwards Brothers, Ann Arbor, Michigan, 1846.
(3) (a) Robinson, THIS JOURNAL, paper 2, 69, 1942 (1947): (b) ilaper 3. 69, 1944 (1947). (1) Claus and Raps, J . 3rakl. Chem., ( 2 ) 45, 211 (1892); Claus
and Seeleman. ihid . 52, 1 (1895).
acid.j By sulfonation a t 300' acid I1 was the chief product. This acid on caustic fusion yielded a hydroxyisoquinoline of m. p. 184" whose struc- ture was not known. We repeated the prepara- tion of this hydroxyisoquinoline with the hope that it would be the 8-hydroxyisoquinoline. The sulfonation of isoquinoline (A), carried out a t 300" as suggested by Claus, produced about 35% of isoquinoline-5-sulfonic acid which could be sepa- rated by means of a difficultly soluble calcium salt. The residue of soluble calcium salts which was evidently a mixture could not be resolved into its pure components. By converting this mix- ture to the sodium salts and fusing with 60y0 so- dium hydroxide a new hydroxyisoquinoline was obtained in an over-all yield of 15%. This new hydroxyisoquinoline melted at 213'; it was en- tirely pure and showed no tendency to be unstable as suggested by Claus. It was different from the known 5 - and 7-hydroxyisoquinoline and from 6- hydroxyisoquinoline which was prepared by de- methylation of 6-metho~yisoquinoline.~ I t re- acted with ammonium sulfite yielding 85% of an
( 5 ) Tyson, THIS JOURNAL, 61, 183 (1939); Andersag, .Wed. Chem. Abhand l . a . mcd. chcm., 2, 377 (1934); Claus and Gutzeit, J . p r n k l Chem., [Z] 52, 9 (1895).
(6) Robinson, i b i d . , paper 1. 69, 1939 (1947).
