Efficient Synthesis of Hantzsch Esters and Polyhydroquinoline Derivatives in Aqueous Micelles

Abstract

Hantzsch 1,4-dihydropyridine and polyhydroquinoline derivatives were synthesized in excellent yields in aqueous micelles. The reaction is catalyzed by PTSA and strongly accelerated by ultrasonic irradiation.

Hantzsch esters - polyhydroquinoline derivatives - aqueous micelles - PTSA

References and Notes

<A NAME="RD18307ST-1A">1a</A> Bossert F. Meyer H. Wehinger E. Angew. Chem., Int. Ed. Engl.  1981,  20:  762 

<A NAME="RD18307ST-1B">1b</A> Nakayama H. Kosoaka Y. Heterocycles  1996,  42:  901 

<A NAME="RD18307ST-1C">1c</A> Godfraid T. Miller R. Wibo M. Pharmacol. Rev.  1986,  38:  321 

<A NAME="RD18307ST-1D">1d</A> Mannhold R. Jablonka B. Voigdt W. Schoenafinger K. Schravan K. Eur. J. Med. Chem.  1992,  229 

<A NAME="RD18307ST-2A">2a</A> Buhler FR. Kiowski W. J. Hypertens.  1987,  5:  S3 

<A NAME="RD18307ST-2B">2b</A> Reid GL. Meredith PA. Pasanisi F. J. Cardiovasc. Pharmacol.  1985,  7:  S18 

<A NAME="RD18307ST-3A">3a</A> Sausins A. Duburs G. Heterocycles  1988,  27:  279 

<A NAME="RD18307ST-3B">3b</A> Mager PP. Coburan RA. Solo AJ. Trigle DJ. Rothe H. Drug Des. Discovery  1992,  8:  273 

<A NAME="RD18307ST-3C">3c</A> Clusa V. Drugs Future  1995,  20:  135 

<A NAME="RD18307ST-3D">3d</A> Boer R. Gekeler V. Drugs Future  1995,  20:  499 

<A NAME="RD18307ST-4A">4a</A> Ruppert R. Jeandon C. Sgambati A. Callot HJ. Chem. Commun.  1999,  2123 

<A NAME="RD18307ST-4B">4b</A> Menche D. Hassfeld J. Li J. Menche G. Ritter A. Rudolph S. Org. Lett.  2006,  8:  741 

<A NAME="RD18307ST-4C">4c</A> Garden SJ. Guimarães CRW. Corréa MB. Oleveira CAFD. Pinto ADC. Alencastro RBD. J. Org. Chem.  2003,  68:  8815 

<A NAME="RD18307ST-4D">4d</A> Quellet SG. Tuttle JB. MacMillan DWC. J. Am. Chem. Soc.  2005,  127:  32 

<A NAME="RD18307ST-4E">4e</A> Martin NJA. List B. J. Am. Chem. Soc.  2006,  128:  13368 

<A NAME="RD18307ST-5A">5a</A> Love B. Sander KM. J. Org. Chem.  1965,  30:  1914 

<A NAME="RD18307ST-5B">5b</A> Hantzsch A. Ber. Dtsch. Chem. Ges.  1888,  21:  942 

<A NAME="RD18307ST-6A">6a</A> Chari MA. Syamasundar K. Catal. Commun.  2005,  6:  624 

<A NAME="RD18307ST-6B">6b</A> Gordeev MF. Patel DV. Gordon EM. J. Org. Chem.  1996,  61:  924 

<A NAME="RD18307ST-6C">6c</A> Yadav JS. Reddy BVS. Basak AK. Narasaiah AV. Green Chem.  2003,  5:  3 

<A NAME="RD18307ST-6D">6d</A> Maquestiau A. Maeyence A. Eynde JJV. Tetrahedron Lett.  1991,  32:  3839 

<A NAME="RD18307ST-6E">6e</A> Ohberg L. Westman J. Synlett  2001,  1296 

<A NAME="RD18307ST-6F">6f</A> Anniyappan M. Muralidharan D. Perumal PT. Synth. Commun.  2002,  32:  659 

<A NAME="RD18307ST-7A">7a</A> Ko S. Yao C.-F. Tetrahedron  2006,  62:  7293 

<A NAME="RD18307ST-7B">7b</A> Heravi MM. Bakhtiari K. Javadi NM. Bamoharram FF. Saeedi M. Oskooie HA. J. Mol. Catal. A.: Chem.  2007,  264:  50 

<A NAME="RD18307ST-7C">7c</A> Kumar A. Maurya RA. Tetrahedron  2007,  63:  1946 

<A NAME="RD18307ST-7D">7d</A> Wang L.-M. Sheng J. Zhang L. Han J.-W. Fan Z.-Y. Tian H. Qian C.-T. Tetrahedron  2005,  61:  1539 

<A NAME="RD18307ST-8">8</A>

Typical Experimental Procedure for the Synthesis of 1,4-Dihydropyridine Derivatives
In a 25 mL round-bottomed flask, benzaldehyde (1 mmol), ethyl acetoacetate (2 mmol), NH₄OAc (1 mmol), and PTSA (0.1 mmol) was added. To this an aqueous solution of SDS (3 mL, 0.1 M) was added. The reaction mixture was immersed in an ultrasonic bath and irradiated for 1 h. Then, the reaction mixture was diluted with brine and extracted with EtOAc. The organic layer was dried over anhyd Na₂SO₄ and concentrated to give a crude product. The pure product was obtained by crystallization of the crude material from MeOH; mp 158 °C. ¹H NMR (200 MHz, CDCl₃): δ = 1.21 (t, J = 7.7 Hz, 6 H), 2.29 (s, 6 H), 4.08 (q, J = 7.7 Hz, 4 H), 4.98 (s, 1 H), 6.00 (s, 1 H), 7.01-7.26 (m, 5 H). IR (KBr): 3322, 1676, 1633 cm^-1. MS: m/z = 330 [M + H]⁺. Anal. Calcd for C₁₉H₂₃NO₄: C, 69.28, H, 7.04, N, 4.25. Found: C, 69.12, H, 6.98, N, 4.14.

<A NAME="RD18307ST-9">9</A>

Typical Experimental Procedure for the Synthesis of Polyhydroquinoline Derivatives
In a 25 mL round-bottomed flask, dimedone (1 mmol), benzaldehyde (1 mmol), ethyl acetoacetate (1 mmol), NH₄OAc (1 mmol), and PTSA (0.1 mmol) was added. To this an aqueous solution of SDS (3 mL, 0.1 M) was added. The reaction mixture was immersed in an ultrasonic bath and irradiated until reaction was complete (TLC monitoring, 1-3 h). The reaction mixture was diluted with brine and extracted with EtOAc. The organic layer was dried over anhyd Na₂SO₄ and concentrated to give a crude product. The pure product was obtained by crystallization from MeOH; mp 203-204 °C. ¹H NMR (300 MHz, CDCl₃): δ = 0.94 (s, 3 H), 1.07 (s, 3 H), 1.21 (t, J = 7.1 Hz, 3 H), 2.13-2.29 (m, 4 H), 2.35 (s, 3 H), 4.06 (q, J = 7.1 Hz, 2 H), 5.07 (s, 1 H), 6.64 (s, 1 H), 7.08-7.13 (m, 1 H), 7.18-7.23 (m, 2 H), 7.28-7.33 (m, 2 H). ¹³C NMR (75 MHz, CDCl₃): δ = 12.92, 17.96, 25.84, 28.15, 31.38, 35.33, 39.65, 49.50, 58.52, 104.72, 110.70, 124.74, 126.59, 126.72, 142.41, 145.82, 147.47, 166.24, 194.43. IR (KBr): 3287, 3078, 2963, 1697, 1611
cm^-1. MS: m/z = 340 [M + H]⁺. Anal. Calcd for C₂₁H₂₅NO₃: C, 74.31, H, 7.42, N, 4.13. Found: C, 74.27, H, 7.39, N, 4.08.