N,O-Bis(trimethylsilyl)acetamide (BSA) is a highly reactive silylating agent widely used in organic synthesis, pharmaceutical chemistry, and analytical chemistry (particularly in gas chromatography-mass spectrometry, GC-MS). It is structurally similar to BSTFA (N,O-bis(trimethylsilyl)trifluoroacetamide) but differs in the absence of a trifluoromethyl group, making it less volatile and more suitable for certain derivatization applications.

1. Key Properties

• Chemical Formula: C₈H₂₁NOSi₂

• Molecular Weight: 203.43 g/mol

• Appearance: Colorless to pale yellow liquid

• Boiling Point: ~71–73°C (at reduced pressure)

• Density: ~0.83 g/cm³

• Solubility: Miscible with common organic solvents (e.g., THF, DCM, hexane), reacts violently with water.

2. Primary Applications

(1) Derivatization in GC-MS Analysis

• Used to silylate polar compounds (e.g., alcohols, carboxylic acids, amines) for improved volatility and thermal stability.

• Example reaction with a hydroxyl group:
  $\mathrm{R}-\mathrm{O}\mathrm{H}+\mathrm{B}\mathrm{S}\mathrm{A}\stackrel{}{\to }\mathrm{R}-\mathrm{O}\mathrm{S}\mathrm{i}(\mathrm{C}\mathrm{H}{\phantom{}}_3){\phantom{}}_3+\mathrm{C}\mathrm{H}{\phantom{}}_3\mathrm{C}\mathrm{O}\mathrm{N}\mathrm{H}\mathrm{S}\mathrm{i}(\mathrm{C}\mathrm{H}{\phantom{}}_3){\phantom{}}_3$

(2) Protecting Group in Organic Synthesis

• Temporarily protects -OH, -NH, -SH groups during multistep synthesis.

• Example: Selective silylation of amino acids before peptide coupling.

(3) Pharmaceutical Intermediates

• Used in the synthesis of steriods, nucleosides, and antibiotics where moisture-sensitive intermediates require protection.

3. Advantages Over Other Silylating Agents

Why choose BSA?

• Milder byproducts (acetamide derivatives) compared to BSTFA (trifluoroacetamide).

• Better for heat-sensitive compounds due to lower volatility than BSTFA.

4. Safety & Handling

• Hazard Class: Flammable liquid (UN 2924), reacts violently with water.

• Storage: Under dry inert gas (N₂/Ar) at 2–8°C to prevent hydrolysis.

• Protection: Use gloves, goggles, and fume hood due to corrosive fumes.

5. Commercial Availability

• Suppliers: Sigma-Aldrich, TCI Chemicals, Alfa Aesar.

• Common Grades: ≥98% purity (GC-MS grade available).

Conclusion

BSA is a versatile silylation reagent offering a balance between reactivity and safety, making it ideal for GC-MS derivatization, protecting group chemistry, and pharmaceutical synthesis. Its lower volatility and milder byproducts compared to BSTFA make it preferable for certain lab-scale and industrial applications.