Formaldehyde → HCID 15673976, compound

HRID 1200174Notes

Reaction equation

HRID 1200174 reaction equation
[CH3:1][C@:2]12[CH2:19][CH2:18][C@H:17]3[C@@H:7]([CH2:8][CH2:9][C:10]4[C@:15]3([CH3:16])[CH2:14][CH2:13][C:12](=[O:20])[CH:11]=4)[C@@H:6]1[CH2:5][CH2:4][C:3]2=[O:21].[C:22]1([SH:28])[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.[CH2:29]=O.[OH-].[Na+]>CCOCC.C(O)C.C(N(CC)CC)C>[C:22]1([S:28][CH2:29][C:11]2[C:12](=[O:20])[CH2:13][CH2:14][C@@:15]3([CH3:16])[C:10]=2[CH2:9][CH2:8][C@@H:7]2[C@@H:17]3[CH2:18][CH2:19][C@@:2]3([CH3:1])[C@H:6]2[CH2:5][CH2:4][C:3]3=[O:21])[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

8

Reactant 4

HCID 712FormaldehydeHCID 6128AndrostenedioneHCID 7969ThiophenolHCID 14798Sodium Hydroxide

Product 1

HCID 15673976HCID 15673976, compound

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 3283Diethyl EtherSolventHCID 8471TriethylamineSolvent

Procedure

Alternatively, a mixture of androst-4-ene-3,17-dione, thiophenol, 40% aqueous formaldehyde, triethylamine and ethanol was heated under reflux for a period of about 48 hours. The cooled solution was poured onto an aqueous sodium hydroxide solution and the product isolated by ether extraction. The ether extracts were washed with water and dried over magnesium sulfate. The resulting residue was triturated with hexane to remove any condensation by-product derived from the thiophenol and formaldehyde. The 4-phenylthiomethylandrost-4-ene-3,17-dione so obtained was desulfurized by dissolving in acetone and adding to a suspension of Raney Nickel in refluxing acetone. The mixture was refluxed for about 5 hours under stirring. The hot solution was filtered and the catalyst washed with boiling ethanol and water. The combined filtrates were concentrated under vacuum whereupon the product separated as a solid mass. Recrystallization from acetone/hexane yielded 4-methylandrost-4-ene-3,17-dione. A mixture of sodium acetate (1 g), absolute chloroform (30 ml), formaldehyde diethyl acetal (30 ml, 0.24 mol), phosphoryl chloride (3.8 ml, 0.04 mol), and 4-methylandrost-4-ene-3,17-dione (0.81 g, 2.7 mmol) was refluxed for about 7 hours, i.e. until the starting material has disappeared. The suspension was allowed to cool and under vigorous stirring a saturated sodium carbonate solution was added dropwise until the pH of the aqueous layer became alcaline (~1 hour). The organic layer was separated, neutralized with water, and dried over sodium sulfate. After concentration under reduced pressure the oily residue was purified by chromatography on silica gel using hexane/ethylacetate as eluent. Thus the pure 4-methyl-6-methylenandrost-4-ene-3,17-dione was obtained in 60% yield; I.R. (KBr): 3080 (6=CH2), 1735 (17-oxo), 1665 (3-oxo), 1635, 1595 cm-1 (Δ4 and 6=CH2).

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for a period of about 48 hours
  3. washThe ether extracts were washed with water
  4. dry with materialdried over magnesium sulfate
  5. customThe resulting residue was triturated with hexane
  6. customto remove any condensation by-product

Sources & evidence

ORD record
ord-b17649b0e38f4d57a25ec6cfd51f4aa8
Source dataset
uspto-grants-1990_02
Patent number
US04904650

Reaction notes

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