Vanillin → Avenanthramide E

HRID 2175681Notes

Reaction equation

HRID 2175681 reaction equation
N1CCCCC1.[OH:7][C:8]1[CH:15]=[CH:14][C:11]([CH:12]=O)=[CH:10][C:9]=1[O:16][CH3:17].C([CH2:21][C:22]([NH:24][C:25]1[CH:33]=[CH:32][CH:31]=[CH:30][C:26]=1[C:27]([OH:29])=[O:28])=[O:23])(O)=O>C1(C)C=CC=CC=1>[OH:7][C:8]1[CH:15]=[CH:14][C:11](/[CH:12]=[CH:21]/[C:22]([NH:24][C:25]2[CH:33]=[CH:32][CH:31]=[CH:30][C:26]=2[C:27]([OH:29])=[O:28])=[O:23])=[CH:10][C:9]=1[O:16][CH3:17]

Participants

5

Reactant 3

HCID 1183VanillinHCID 8082PiperidineHCID 4399222-(2-Carboxyacetamido)benzoic acid

Product 1

HCID 10245047Avenanthramide EYield 78%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Piperidine (0.50 mL, 5.1 mmol) was added to a suspension of 4-hydroxy-3-methoxybenzaldehyde (0.77 g, 5.1 mmol) and 2-[(carboxyacetyl)amino]benzoic acid (1.0 g, 4.5 mmol) in toluene (5.0 mL). The reaction flask was fitted with a Dean-Stark apparatus and heated to reflux for 3 h, then cooled to rt and the resulting suspension was filtered and washed with toluene. The piperidinium salt was dissolved in MeOH (12.0 mL) and water (12.0 mL) at 40° C. and the solution was acidified with concentrated HCl. The precipitate was filtered, providing (E)-2-[[3-(4-hydroxy-3-methoxyphenyl)-1-oxo-2-propenyl]amino]benzoic acid (1.1 g, 78%) as a yellow crystalline solid; mp 207.5-208.5° C., lit.5 230-233° C.; δH (500 MHz, DMSO-d6) 3.83 (s, 3H, OCH3), 6.71 (d, J=15.5 Hz, 1H, CH═CHCO), 6.80 (d, J5′,6=8.5 Hz, 1H, H5′), 7.13 (dd, J5,6=8.5, J2′,6′=1.5 Hz, 1H, H6′), 7.15 (t, J3,4=J4,5=8.0 Hz, 1H, H4), 7.34 (d, J2′,6′=1.5 Hz, 1H, H2′), 7.52 (d, J=15.5 Hz, 1H, CH═CHCO), 7.60 (td, J4,5=J5,6=8.0, J3,5=2.0 Hz, 1H, H5), 8.00 (dd, J3,4=8.0, J3,5=2.0 Hz, 1H, H3), 8.62 (d, J5,6=8.0 Hz, 1H, H6), 9.57 (s, 1H, OH), 11.27 (s, 1H, NH), 13.61 (br s, 1H, CO2H).

Workup

  1. customThe reaction flask was fitted with a Dean-Stark apparatus
  2. temperatureheated
  3. temperatureto reflux for 3 h
  4. filtrationthe resulting suspension was filtered
  5. washwashed with toluene
  6. dissolutionThe piperidinium salt was dissolved in MeOH (12.0 mL)
  7. customat 40° C.
  8. filtrationThe precipitate was filtered

Sources & evidence

ORD record
ord-613b5ec8d17c4d34a4af46d6b5b08bb0
Source dataset
uspto-grants-2015_06
Patent number
US09062076B2

Reaction notes

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