Aromatic Electrophilic Substitution vs. Intramolecular Wittig Reaction: Vinyltriphenylphosphonium Salt Mediated Synthesis of 4-Carboxyalkyl-8-formyl Coumarins

Abstract

4-Carboxyalkyl-8-formyl coumarins have been synthesized from 2-hydroxybenzaldehydes via vinyltriphenylphosphonium salt mediated aromatic electrophilic substitution in good yields. The vinyltriphenylphosphonium salt is generated in situ by protonation of the reactive 1:1 intermediate produced by the reaction of triphenylphosphine and dialkyl acetylenedicarboxylate with 2-hydroxybenzaldehydes.

Keywords

4-carboxyalkyl-8-formyl coumarin - diethyl acetylenedicarboxylate - dimethyl acetylenedicarboxylate (DMAD) - 2-hydroxybenzaldehyde - vinyltriphenylphosphonium salt - aromatic electrophilic substitution

References and Notes

• 1 Chakraborty DP. Das Gupta A. Bose PK. Ann Biochem. Exp. Med.  1957,  17:  57 
• 2a Arora RB. Mathur CN. Br. J. Pharmacol.  1963,  20:  29 
• 2b Link KP. Harvey Lect.  1943,  39:  162 
• 3 Willette RE. Soine TO. J. Pharm. Sci.  1962,  51:  149 
• 4 Molho D, Boschetti E, and Fontaine L. inventors; US  3175943.  ; Chem. Abstr. 1966, 64, 14040a
• 5 Schonberg A. Latif N. J. Am. Chem. Soc.  1954,  7:  6208 
• 6 Kadis S. Cigler A. Ajl S. Microb. Toxins  1972,  7:  1 
• 7 Ellis GP. West GB. Prog. Med. Chem.  1974,  10:  109 
• 8 Holfmann R. Wells P. Morrison H. J. Org. Chem.  1971,  36:  102 
• 9 Wells P. Morrison H. J. Am. Chem. Soc.  1975,  97:  154 
• 10a Kostova I. Curr. Med. Chem.  2005,  5:  29 
• 10b Campagne JM. Six Y. Science of Synthesis   Vol. 26:  Thieme; Stuttgart: 2004.  p.989 
• 10c Borges F. Roleira F. Milhazes N. Santana L. Uriarte E. Curr. Med. Chem.  2005,  12:  887 
• 11 Murray RDH. Mendez J. Brown SA. The Natural Coumarins: Occurrence, Chemistry and Biochemistry   Wiley; New York: 1982. 
• 12a Von Pechmann H. Duisberg C. Ber. Dtsch. Chem.  1883,  16:  2119 
• 12b Von Pechmann H. Ber. Dtsch. Chem. Ges.  1884,  17:  929 
• 12c John EVO. Israelstam SS.
  J. Org. Chem.  1961,  26:  240 
• 12d Rao YVS. Kulkarni SJ. Subramanyam M. Rao AVR. J. Chem. Soc., Chem. Commun.  1993,  1456 
• 13a Jones G. Org. React.  1976,  15:  204 
• 13b Adams R. Bockstahler TE. J. Am. Chem. Soc.  1952,  74:  5346 
• 13c Brufola G. Fringuelli F. Piermatti O. Pizzo F. Heterocycles  1996,  43:  1257 
• 13d Kadin SB. J. Org. Chem.  1966,  31:  620 
• 14 Johnson JR. Org. React.  1942,  1:  210 
• 15 Shriner RL. Org. React.  1942,  1:  1 
• 16 Woods LL. Sapp J. J. Org. Chem.  1962,  27:  3703 
• 17a Simonis H. Remmert P. Ber. Dtsch. Chem. Ges.  1914,  47:  2229 
• 17b Robertson A. Sandrock WF. Hendry CB. J. Chem. Soc.  1931,  2426 
• 18 Sethna SM. Shah NM. Shah RC. J. Chem. Soc.  1938,  228 
• 19a Potdar MK. Mohile SS. Salunkhe MM. Tetrahedron Lett.  2001,  42:  9285 
• 19b Potdar MK. Rasalkar MS. Mohile SS. Salunkhe MM. J. Mol. Catal. A: Chem.  2005,  235:  249 
• 20a Rodríguez-Domínguez JC. Kirsch G. Tetrahedron Lett.  2006,  47:  3279 
• 20b Reddy BM. Patil MK. Lakshmanan PP. J. Mol. Catal. A: Chem.  2006,  256:  290 
• 20c Selvakumar S. Chidambaram M. Singh AP. Catal. Commun.  2007,  8:  777 
• 21 Bose DS. Rudradas AP. Babu MH. Tetrahedron Lett.  2002,  43:  9195 
• 22 Kadnikov DV. Larock RC. Org. Lett.  2000,  2:  3643 
• 23 Rajintha B. Naveen Kumar V. Someshwar P. Venu Madhav J. Narsimha Reddy P. Thirupathi Reddy Y. ARKIVOC  2006,  (xii):  23 
• 24 Livant P. Xu W. J. Org. Chem.  1998,  63:  636 ; and references cited therein
• 25a Khandekar AC. Khadilkar BM. Synlett  2002,  152 
• 25b Gu Y. Zhang J. Duan Z. Deng G. Adv. Synth. Catal.  2005,  347:  512 
• 26a Yavari I. Hekmat-Shoar R. Zonouki A. Tetrahedron Lett.  1998,  39:  2391 
• 26b Yavari I. Adib M. Hojabri L. Tetrahedron  2001,  57:  7537 
• 26c Yavari I. Abbasinejad A.-M. Hossaini Z. Org. Biomol. Chem.  2003,  1:  560 
• 26d Galariniotou E. Fragos V. Makri A. Litinas KE. Nicolaides DN. Tetrahedron  2007,  63:  8298 
• 26e Kumar P. Upadhyay PK. Tetrahedron Lett.  2009,  50:  236 
• 27 Kumar P. Bodas MS. Org. Lett.  2000,  2:  3821 
• 28 Hekmat-Shoar R. Souri S. Faridbod F. Phosphorus, Sulfur Silicon Relat. Elem.  2003,  178:  1457 
• 29 Glasnov TN. Ivanov IC. Synth. Commun.  2008,  38:  1579 
• 30 Majumdar KC. Ansary I. Sinha B. Chattopadhyay B. Synthesis  2009,  3593 
• 32 Hekmat-Shoar R. Souri S. Rahimifard M. Faridbod F. Phosphorus, Sulfur Silicon Relat. Elem.  2002,  177:  2827 
• 33 Cobridge DEC. Phosphorus: An Outline of the Chemistry, Biochemistry and Uses   5th ed.:  Elsevier; Amsterdam: 1995. 
• 34a Johnson AW. Tebby JC. J. Chem. Soc.  1961,  2126 
• 34b Caesar JC. Griffiths DV. Griffiths PA. Tebby JC. J. Chem. Soc., Perkin Trans. 1  1989,  1:  2425 

31

Synthesis of Ethyl 8-formyl-2-oxo-2 H -chromene-4-carboxylate (6a)
A mixture of 2-hydroxybenzaldehyde (4a, 200 mg, 0.81 mmol) and Ph₃P (320 mg, 1.22 mmol) in DMF (7 mL) was stirred at r.t. for 10 min in a 25 mL round-bottom flask. A solution of diethyl acetylenedicarboxylate (206 mg, 1.22 mmol) in DMF (3 mL) was added dropwise for another 10 min, and the dark-brown coloured solution thus obtained was heated at 50 ˚C for 12 h. Then the reaction mixture was extracted with CH₂Cl₂ (3 × 20 mL), washed with H₂O (4 × 20 mL), brine (20 mL), and dried over anhyd Na₂SO₄. The solvent was removed under reduced pressure to give a crude mass, and the product was isolated by silica gel (230-400 mesh) column chromatography using a mixture of EtOAc-PE (1:9) as an eluent, and pure product 6a was obtained as a solid, yield 82%; mp 117-118 ˚C. IR (KBr): 1699, 1725, 1746 cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 1.46 (t, 3 H, J = 7.2 Hz, CH₂CH ₃), 4.49 (q, 2 H, J = 6.8 Hz, CH ₂CH₃), 7.06 (s, 1 H, C3H of coumarin), 7.46 (t, 1H, J = 8.0 Hz, ArH), 8.14 (dd, 1 H, J = 7.6, 1.2 Hz, ArH), 8.59 (dd, 1 H, J = 8.0, 1.2 Hz, ArH), 10.73 (s, 1 H, CHO). ^¹³C NMR (100 MHz, CDCl₃): δ = 14.1, 62.9, 116.6, 119.8, 123.8, 124.7, 130.9, 133.0, 142.2, 155.5, 158.3, 163.3, 187.1. HRMS: m/z calcd for C₁₃H₁₀O₅: 269.0426 [M + Na]⁺. Found: 269.0429 [M + Na]⁺. Anal. Calcd (%) for C₁₃H₁₀O₅: C, 63.42; H, 4.09. Found: C, 62.91; H, 4.10.