Phthalide → HCID 86733983, compound

HRID 1576495Notes

Reaction equation

HRID 1576495 reaction equation
[C:1]1([CH:7]([C:11]([OH:13])=[O:12])[C:8]([OH:10])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.S(Cl)(Cl)=O.[K+].[Br-].[C:20]1([C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH2:23][O:22]1)=[O:21]>CCOCC.CN(C)C=O.C1(CC(O)=O)C=CC=CC=1.C1(C2C(=CC=CC=2)CO1)=O>[C:1]1([CH:7]([C:11]([OH:13])=[O:12])[C:8]([OH:10])=[O:9])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1.[C:20]1([C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH2:23][O:22]1)=[O:21]

Participants

8

Reactant 4

HCID 6885PhthalideHCID 24386Thionyl ChlorideHCID 75791Phenylmalonic acidHCID 253877Potassium Bromide

Product 1

HCID 86733983HCID 86733983, compoundYield 48.5%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 3283Diethyl EtherSolventHCID 86733984HCID 86733984, compoundSolvent

Procedure

Phenylmalonic acid (12.6 g; 0.07 M) and thionyl chloride (5.2 ml.; 0.07 M) were heated under reflux for 2 hrs. in anhydrous ether (50 ml.) containing 1-2 drops of dimethylformamide. At the end of this period the solvent and any remaining thionyl chloride were removed in vacuo. The oily residue was dissolved in anhydrous ether (75 ml.), o-phthalaldehydic acid (10.5g; 0.07 M) was added in one portion and the mixture heated under reflux for 2 hrs. The yellow reaction solution was cooled to ambient temperatures and extracted with saturated sodium bicarbonate solution (150 ml.) and the bicarbonate solution quickly washed with ether (100 ml.) and acidified to pH 1.0 with 5N hydrochloric acid (NB the bicarbonate layer should be made acidic as quickly as possible due to the lability of the phthalide ester group at alkaline pH values). A yellow oil precipitated out of the acidic solution and it was extracted into methylene dichloride (2×100 ml.) and the organic extracts were washed with water (2×100 ml.) and dried over anhydrous magnesium sulphate. Upon concentrating the dried methylene solution in vacuo to ca. 1/4 volume the product crystallised as a white solid (6.0g.), m.p. 130°-131°. A second crop was obtained (4.6g.) m.p. 128°-130°, representing a total yield of 48.5%. i.r. (KBr) strong bands inter alia at: 1770cm-1 1700 cm-1 1420 cm-1 1275 cm-1 1265 cm- 1 1215 cm-1 1145 cm-1 1050 cm-1 960 cm-1 750 cm-1 695 cm-1 n.m.r. [(CD3)2CO/D2O]: δ= 7.9-7.3 (1 OH. multiplet. phenyl and phthalide aromatics and ##EQU4## δ= 4.97(1H.s. ##EQU5## Upon standing a third peak developed at δ= 3.83 which is the methylene group in phthalide phenyl acetate formed by decarboxylation of phthalide hydrogen phenylmalonate.

Workup

  1. temperatureunder reflux for 2 hrs
  2. customAt the end of this period the solvent and any remaining thionyl chloride were removed in vacuo
  3. dissolutionThe oily residue was dissolved in anhydrous ether (75 ml.)
  4. additiono-phthalaldehydic acid (10.5g; 0.07 M) was added in one portion
  5. temperaturethe mixture heated
  6. temperatureunder reflux for 2 hrs
  7. temperatureThe yellow reaction solution was cooled to ambient temperatures
  8. extractionextracted with saturated sodium bicarbonate solution (150 ml.)
  9. washthe bicarbonate solution quickly washed with ether (100 ml.)
  10. customA yellow oil precipitated out of the acidic solution and it
  11. extractionwas extracted into methylene dichloride (2×100 ml.)
  12. washthe organic extracts were washed with water (2×100 ml.)
  13. dry with materialdried over anhydrous magnesium sulphate
  14. concentrationUpon concentrating the dried methylene solution in vacuo to ca. 1/4 volume the product
  15. customcrystallised as a white solid (6.0g.), m.p. 130°-131°
  16. customA second crop was obtained (4.6g.) m.p. 128°-130°

Sources & evidence

ORD record
ord-421b7734a45b431a96d29bdf6b503917
Source dataset
uspto-grants-1976_09
Patent number
US03981866

Reaction notes

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