IJOC  Vol.3 No.4 , December 2013
Synthesis of N-Benzyl-3-anilinopropanamides and Cyclization to 4-Hydroxy-4-N-benzylamino-1,2,3,4-tetrahydroquinoline
ABSTRACT

Substituted 3-anilinopropanamides were converted to N-benzyl derivatives via uncatalyzed amine exchange reaction with benzylamine in up to 41% yield. Unprotected aniline nitrogen had been observed to inhibit facile cyclization. An attempt was therefore made to protect the N by acetylation prior to cyclization. During this process, facile ring closure occurred in the methoxy series to give 4-hydroxy-4-N-benzylamino-1,2,3,4-tetrahydroquinolines in up to 69% yield.

 

 


Cite this paper
L. Nnamonu, V. Agwada and C. Nwadinigwe, "Synthesis of N-Benzyl-3-anilinopropanamides and Cyclization to 4-Hydroxy-4-N-benzylamino-1,2,3,4-tetrahydroquinoline," International Journal of Organic Chemistry, Vol. 3 No. 4, 2013, pp. 229-234. doi: 10.4236/ijoc.2013.34032.
References
[1]   A. R. Katritzky, S. Rachwal and B. Rachwal, “Recent Progress in the Synthesis of 1,2,3,4-Tetrahydroquinolines,” Tetrahedron Letters, Vol. 52, No. 48, 1996, pp. 1503115070. http://dx.doi.org/10.1016/S0040-4020(96)00911-8

[2]   B. S. Slusher, K. C. Rissolo, P. F. Jackson and L. M. Pullan, “Centrally-Administered Glycine Antagonists Increase Locomotion in Monoamine-Depleted Mice,” Journal of Neural Transmission. General Section, Vol. 97, No. 3, 1994, pp. 175-185.
http://dx.doi.org/10.1007/BF02336139

[3]   Y. Yoneda, T. Suzuki, K. Ogita and D. Han, “Support for Radio Labelling of a Glycine Recognition Domain on the N-Methyl-D-aspartate Receptor Ionophore Complex by 5,7-[3H]dichlorokynurenate in Rat Brain,” Journal of Neurochemistry, Vol. 60, No. 2, 1994, pp. 634-645.
http://dx.doi.org/10.1111/j.1471-4159.1993.tb03195.x

[4]   T. Nishiyama, Y. Hashiguchi, S. Sakata and T. Sakaguchi, “Antioxidant Activity of the Fused Heterocyclic Compounds, 1,2,3,4-Tetrahydroquinolines, and Related Compounds-Effect of Ortho-Substituents,” Polymer Degradation and Stability, Vol. 79, No. 2, 2003, pp. 225-230.
http://dx.doi.org/10.1016/S0141-3910(02)00285-9

[5]   V. Getautis, A. Stanisauskaite, T. Malinauskas, J. Stumbraite, V. Gaidelis and V. Jankauskas, “Hydrazones Possessing a Phenyl-1,2,3,4-tetrahydroquinoline Moiety as Hole Transporting Materials,” Monatshefte für Chemie/ Chemical Monthly, Vol. 137, No. 11, 2006, pp. 1401-1409.

[6]   V. Getautis, J. Stumbraite, V. Gaidelis, V. Jankauskas, A. Kliucius and V. Paulauskas, “Molecular Glasses Possessing a Phenyl-1,2,3,4-tetrahydroquinoline Moiety as Hole Transporting Materials for Electrophotography,” Synthetic Metals, Vol. 157, No. 1, 2007, pp. 35-40.
http://dx.doi.org/10.1016/j.synthmet.2006.12.001

[7]   V. V. Kouznetsov, C. M. Gómez, L. K. Parada, J. H. Bermuda, L. K. Méndez and A. M. Acevedo, “Efficient Synthesis and Free-Radical Scavenging Capacity of New 2,4-Substituted Tetrahydroquinolines Prepared via BiCl3-Catalyzed Three-Component Povarov Reaction, Using N-Vinylamides,” Molecular Diversity, Vol. 15, No. 4, 2011, pp. 1007-1016.
http://dx.doi.org/10.1007/s11030-011-9330-5

[8]   C. S. Yi and S. Y. Yun, “Ruthenium-Catalyzed Intermolecular Coupling Reactions of Arylamines with Ethylene and 1,3-Dienes: Mechanistic Insight on Hydroamination vs Ortho-C-H Bond Activation,” Organic Letters, Vol. 7, 2005, pp. 2181-2183.
http://dx.doi.org/10.1021/ol050524+

[9]   Y. Luo, Z. Li and C.-J. Li, “A Silver-Catalyzed Domino Route toward 1,2-Dihydroquinoline Derivatives from Simple Anilines and Alkynes,” Organic Letters, Vol. 7, 2005, pp. 2675-2678. http://dx.doi.org/10.1021/ol050826b

[10]   T. Nishio, M. Tabata, H. Koyama and M. Sakamoto, “Photochemistry of N-(2-Acylphenyl)-2-methylprop-2-enamides: Competition between Photocyclization and Long-Range Hydrogen Abstraction,” Helvetica Chimica Acta, Vol. 88, No. 1, 2005, pp. 78-86.
http://dx.doi.org/10.1002/hlca.200490298

[11]   G.-D. Isabelle, P. Gastaud and T. V. Rajan Babu, “Asymmetric Synthesis of Functionalized 1,2,3,4-Tetrahydroquinolines,” Organic Letters, Vol. 3, No. 13, 2001, pp. 2053-2056. http://dx.doi.org/10.1021/ol016018b

[12]   M. Rueping, T. Theissmann, M. Stoeckel and A. P. Antonchick, “Direct Enantioselective Access to 4-Substituted Tetrahydroquinolines by Catalytic Asymmetric Transfer Hydrogenation of Quinolines,” Organic & Biomolecular Chemistry, Vol. 9, No. 19, 2011, p. 6844-6850.
http://dx.doi.org/10.1039/c1ob05870c

[13]   X. Yang, C. Xi and Y. Jiang, “CuCl2-Catalyzed One-Pot Formation of Tetrahydroquinolines from N-Methyl-Nalkylanilines and Vinyl Ethers in the Presence of t-Butylhydroperoxide,” Molecules, Vol. 11, 2006, pp. 978-987. http://dx.doi.org/10.3390/11120978

[14]   R. Degutyte, J. Stumbraite and V. Getautisa, “Synthesis of a Bifunctional 1,2,3,4-Tetrahydroquinoline Derivative: 4,4’-(1,4-Phenylene)di-(1,2,3,4-tetrahydrobenzo[f]quinolin-2-ol),” Archives for Organic Chemistry, No. 7, 2009, pp. 26-32.

[15]   K. Takamura, A. Shioya, T. Yamamoto, S. Takama and Y. Nitta, “Studies on Analgesics of Aniline Series 3. Preparation and Properties of N,N-Dialkyl3-(substituted anilino)butyramide Series,” Chemical & Pharmaceutical Bulletin, Vol. 13, No. 2, 1965, pp. 211-217.
http://dx.doi.org/10.1248/cpb.13.211

[16]   V. C. Agwada and L. A. Nnamonu, “Synthesis of 3-Anilinopropanamides,” Chemical Society of Nigeria, Vol. 37, No. 2, 2012, pp. 98-101.

[17]   R. C. Elderfield, W. J. Gensler, T. H. Bembry, C. B. Kremer, F. Brody, H. A. Hageman and J. D. Head, “Synthesis of Certain Simple 4-Aminoquinoline Derivatives,” Journal of the American Chemistry Society, Vol. 68, No. 7, 1946, pp. 1250-1251. http://dx.doi.org/10.1021/ja01211a032

[18]   A. Y. Idris, M. I. Sule and M. S. Sallau, “Synthesis and Anticonvulsant Studies of Isomeric N-Benzyl-3-anisidinopropanamides (3-[(Methoxyphenyl)amino]propanamides),” Nigerian Journal of Pharmaceutical Sciences, Vol. 8, No. 1, 2009, pp. 118-127.

 
 
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