Preparation of Dimethylmethoxy Chromanol

Dimethylmethoxy Chromanol (DMC) is a chromanol derivative, structurally related to Vitamin E (tocopherols). Its preparation typically involves modification of the chromanol ring, introducing methoxy and methyl groups at specific positions.

General Reaction Scheme

The preparation of Dimethylmethoxy Chromanol usually involves:

1. Chromanol core synthesis

  • Start from a hydroxychroman or tocopherol precursor.

2. Methylation

  • Introduce methyl groups on the phenolic hydroxyls or the chromanol ring.

3. Methoxylation

  • Convert a hydroxyl group (-OH) into a methoxy group (-OCH₃) using a methylating agent.

4. Purification

  • Purify via column chromatography or recrystallization.
Preparation of Dimethylmethoxy Chromanol-Xi'an Lyphar Biotech Co., Ltd

Materials and Reagents

Typical reagents include:

  • Hydroxychromanol or a tocopherol derivative
  • Methyl iodide (CH₃I) or dimethyl sulfate ((CH₃O)₂SO₂) as methylating agents
  • Base: potassium carbonate (K₂CO₃) or sodium hydride (NaH)
  • Solvents: acetone, dichloromethane (Dimethylmethoxy Chromanol), or ethanol
  • Purification agents: silica gel, recrystallization solvents (hexane, ethyl acetate)

Stepwise Synthesis (Representative Method)

Step 1: Activation of Hydroxyl Group

  • Dissolve the chromanol precursor in a dry solvent (e.g., acetone).
  • Add a base (e.g., K₂CO₃) to deprotonate the phenolic hydroxyl.
  • Stir at room temperature until the hydroxyl is fully activated.

Step 2: Methylation

  • Add methyl iodide (CH₃I) dropwise under inert atmosphere (N₂).
  • Stir at room temperature or slightly elevated temperature (30–50°C) for several hours.
  • The phenolic OH group is converted to -OCH₃.

Step 3: Ring Methylation (if required)

  • Additional methyl groups on the chromanol ring can be introduced using alkylation reactions.
  • Commonly done using Friedel–Crafts alkylation with methyl halides in the presence of a Lewis acid (e.g., AlCl₃).

Step 4: Work-Up

  • Quench the reaction with water.
  • Extract with an organic solvent (e.g., Dimethylmethoxy Chromanol).
  • Wash with brine and dry over anhydrous sodium sulfate.
Preparation of Dimethylmethoxy Chromanol-Xi'an Lyphar Biotech Co., Ltd

Step 5: Purification

  • Alternatively, recrystallize from suitable solvents (e.g., hexane or ethanol) to obtain pure Dimethylmethoxy Chromanol as a solid.

Notes

  • Reactions must be carried out under dry conditions to avoid hydrolysis of methylating agents.
  • Methoxylation efficiency depends on base strength and reaction temperature.
  • Avoid excess heat during ring methylation to prevent over-alkylation or decomposition.