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ortho-Hydroxybenzaldehydes
from Phenyl-2-nitropropenes

A Convenient & Short Route for the Synthesis of Ayapin & Scoparone

S.L. Kelkar, C.P. Phadke, S. Marina
Ind. J. Chem. 23B, 458-459 (1984)

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Abstract

A short, convenient and general route to synthesise two important intermediates in coumarin synthesis, viz. 2-hydroxy-4,5-methylenedioxybenzaldehyde (4a) and 2-hydroxy-4,5-dimethoxybenzaldehyde (4b), is described. These have been converted by Wittig reaction into the naturally occurring coumarins, ayapin (1a) and scoparone (1b), respectively.

Three methods are reported1 in literature for the synthesis of ayapin (1a), a naturally occurring coumarin which exhibits hemostatic2 and antibiotic3 activities. These methods involve either longer routes or difficultly available reagents and give 1a in lower yields. We report herein a short and convenient synthesis of 1a using easily available reagents and mild reaction conditions.

Piperonal (2a) was converted into β-methyl-β-nitrostyrene (3a)4 which was treated, as per the recently reported but not the generalised procedure of Royer and coworkers5 , with 2 mol each of acetyl chloride and aluminium chloride in methylene chloride at -30C to give 2-hydroxy- 4,5-methylenedioxybenzaldehyde (4a) in 40% yield. This on refluxing with Ph3P=CHCO2Et in ethylbenzene afforded 1a (Chart 1) in 65% yield.

Similarly, 3,4-dimethoxy-β-methyl-β-nitrostyrene (3b)6 was converted into 2-hydroxy-4,5-dimethoxy- benzaldehyde (4b) in 35% overall yield starting from veratraldehyde (2b). Since 4b has already been converted into scoparone in this laboratory7, this procedure also represents a short and convenient synthesis of scoparone (1b).

Experimental

Hydroxybenzaldehydes (4a,b) from β-methyl-β-nitrostyrenes (3a,b)

A 5% solution of 3a or 3b in methylene chloride, cooled to -30C, was added to a similarly cooled 20% suspension of acetyl chloride (2M) and aluminium chloride (2M) in CH2Cl2. The mixture was stirred for 30 min and poured over ice and 0.1 N HCl. Methylene chloride layer was separated, washed with water and extracted with 1 N NaOH till free from phenol. The aqueous layer was acidified and extracted with ether. The ether layer on drying and removal of solvent, gave 4a or 4b which was characterised as given below:

4a: Yield 40%, yellowish needles from pet. ether, mp 124C (lit.1, mp 125C).
4b: Yield 35%, white needles from pet. ether, mp 104C (lit.7 mp 105C).
      This was found to be identical (m.m.p., IR, co-TLC) with an authentic sample of 4b.

Ayapin (1a)

A mixture of 4a (0.15 g) and Ph3P=CHCO2Et (0.3 g) was refluxed in dry ethylbenzene (5 ml) for 10 h and solvent removed under reduced pressure. The residue as sublimed in vacuo to get a solid (0.35g) which was stirred in aq. ethanol (50%, 10 ml) to dissolve triphenylphosphine oxide8. This on filtration gave 1a (0.14 g) showing blue fluorescence under UV, mp 225C (taken on hot plate with covered slide), sublimes at 170C (lit.1 sublimation temperature 174C, mp 224-225C).

References

  1.  
    1. Späth E, Bose P K & Schlager J, Chem. Ber. 70B, 302 (1937)
    2. Crosby D G & Berthold R V, J. Org. Chem., 27, 3080 (1962)
    3. Kengi F & Mitsuru N, Bull. Chem. Soc. Japan., 35, 1321 (1962)
  2. Bose P K, Sen P B & Chakravarty K, Ann. Biochem. Exptl. Med., 5, 1 (1945); Chem. Abs. 40, 2224 (1948)
  3. Chakraborty D P, Sen M & Bose P K, Trans. Bose. Res. Inst., 24, 31 (1961); Chem. Abs. 56, 1835 (1962)
  4. Seebach D, Leitz H F & Ehrig V, Michael-Additionen von Lithiumenolaten und schwefelsubstituierten Lithiumorganylen an Nitrolefine, Chem. Ber., 108, 1924-1945 (1975)
  5. Guillaumel J, Demerseman P & Royer R, Sur une Transformation Inattendue du β-Methyl-β-Nitrostyrene en Aldehyde Salicylique, Tetrahedron, 37, 4215-4217 (1981)
  6. Gairud C B & Lappin G R, The Synthesis of β-Nitrostyrenes, J. Org. Chem., 18, 1-3 (1953)
  7. Mali R S, Yadav V J & Zaware R N, Indian. J. Chem., 21B, 759 (1982)
  8. Paradkar M V, personal communication.