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trimethylsilyl trifluoromethanesulfonate(TMSOTf) is a widely used reagent in organic synthesis. It combines the reactivity of the trimethylsilyl group with the electrophilic nature of the triflate anion, making it a powerful catalyst and activating agent in a variety of chemical reactions.

Chemical Structure and Properties

Chemical Name: Trimethylsilyl trifluoromethanesulfonate
Abbreviation: TMSOTf
Molecular Formula: C₄H₉F₃O₃SSi
Molecular Weight: 218.27 g/mol
CAS Number: 27607-77-8

Physical Properties:

PropertyDescriptionAppearanceColorless to pale yellow liquidBoiling Point109–111°C (at 20 mmHg)Density~1.29 g/cm³SolubilityMiscible with most organic solventsStabilityReacts with water and alcohols

The molecule consists of a highly electrophilic triflate group (-OSO₂CF₃) and a trimethylsilyl (TMS) group, making it highly reactive in polar and anhydrous conditions.

Synthesis

TMSOTf is typically prepared by reacting trimethylsilyl chloride (TMSCl) with silver trifluoromethanesulfonate (AgOTf) under anhydrous conditions:

$$\text{TMSCl}+\text{AgOTf}\to \text{TMSOTf}+\text{AgCl}$$

The reaction must be performed in the absence of moisture because TMSOTf is hydrolytically unstable.

Applications

1. Catalyst in Organic Synthesis:

   • TMSOTf is an effective Lewis acid and is used to catalyze reactions requiring electrophilic activation.
   • It is widely employed in Friedel-Crafts alkylations, acylations, and other electrophilic aromatic substitution reactions.

2. Silylation Agent:

   • It is used to introduce trimethylsilyl (TMS) groups into alcohols, phenols, and carboxylic acids, protecting these functional groups during multistep syntheses.
   • Example: $$R-OH+\text{TMSOTf}\to R-OTMS+\text{HOTf}$$

3. Activation of Nucleophiles and Electrophiles:

   • TMSOTf enhances the reactivity of carbonyl compounds and other electrophiles, making it useful in reactions such as aldol condensations and Mukaiyama reactions.
   • It can also activate certain nucleophiles like enol ethers, dienes, and ketene acetals.

4. Carbocation Generation:

   • TMSOTf is frequently used to generate carbocations under mild conditions, which are crucial intermediates in cationic polymerization and rearrangement reactions.

5. Glycosylation Reactions:

   • It is a reagent of choice for glycosylation in carbohydrate chemistry, enabling the coupling of sugar donors with acceptors to form glycosidic bonds.
   • Example: $$\text{Sugar donor}+\text{Sugar acceptor}+\text{TMSOTf}\to \text{Glycoside}$$

6. Ring-Closing Reactions:

   • TMSOTf is used in cyclization reactions, such as in the synthesis of heterocyclic compounds and lactones.

7. Reagent for Selective Reactions:

   • Due to its mild reactivity, TMSOTf is often used for selective transformations where harsher conditions may lead to unwanted side reactions.

Advantages

• High Electrophilicity: Enables efficient activation of substrates.
• Mild Reaction Conditions: Operates under relatively low temperatures and pressures.
• Versatility: Useful across a range of organic transformations.

Safety and Handling

TMSOTf is a highly reactive compound and must be handled with care.

Hazards:

• Reacts violently with water to release toxic gases, such as hydrogen fluoride (HF) and triflic acid.
• Causes severe burns upon skin or eye contact.
• Vapors are corrosive to the respiratory system.

Safety Precautions:

• Work in a well-ventilated fume hood.
• Use proper PPE: gloves, goggles, and lab coats.
• Avoid contact with moisture and incompatible substances like strong bases and oxidizers.

First Aid:

• Inhalation: Move to fresh air immediately; seek medical attention.
• Skin/Eye Contact: Wash thoroughly with water; for eye exposure, rinse for at least 15 minutes and seek immediate medical assistance.
• Ingestion: Do not induce vomiting; seek medical help immediately.

Storage:

• Store in a tightly sealed container under anhydrous conditions.
• Keep away from moisture, acids, and bases.

Environmental Impact

TMSOTf is potentially hazardous to aquatic environments and should not be released into the environment. Disposal must comply with local environmental regulations.

Conclusion

Trimethylsilyl trifluoromethanesulfonate (TMSOTf) is a versatile and powerful reagent widely used in organic synthesis, particularly in electrophilic activation and silylation reactions. Its high reactivity and selectivity make it invaluable for various chemical processes, although its handling requires careful precautions due to its corrosive and moisture-sensitive nature.

4-hydroxy Benzyl Alcoholis an organic compound commonly used in chemical and pharmaceutical research. It is a phenolic derivative of benzyl alcohol, containing both a hydroxyl group (-OH) and a benzyl alcohol functional group. These features make it a versatile compound for various synthetic and biological applications.

Chemical Structure and Properties

Chemical Name: 4-Hydroxybenzyl alcohol
Other Names: Para-hydroxybenzyl alcohol, Tyrosol
Molecular Formula: C₇H₈O₂
Molecular Weight: 124.14 g/mol
CAS Number: 623-05-2

Physical Properties:

PropertyDescriptionAppearanceWhite to off-white crystalline solid or powderMelting Point85–87°CBoiling Point285°CSolubilitySoluble in water, ethanol, and other polar solventsOdorMild phenolic odor

The compound's chemical structure features a benzene ring substituted with a hydroxyl group at the para position and a primary alcohol group on the benzyl side chain.

Synthesis

4-Hydroxybenzyl alcohol can be synthesized through various methods, including:

1. Reduction of 4-Hydroxybenzaldehyde: The reduction of 4-hydroxybenzaldehyde using a mild reducing agent such as sodium borohydride (NaBH₄) or catalytic hydrogenation produces 4-hydroxybenzyl alcohol.

   C6H4(OH)CHO+H2→C6H4(OH)CH2OHC₆H₄(OH)CHO + H₂ → C₆H₄(OH)CH₂OHC6​H4​(OH)CHO+H2​→C6​H4​(OH)CH2​OH

2. Biotechnological Synthesis: It can also be produced via microbial or enzymatic pathways, particularly from tyrosine or related precursors, using engineered microorganisms.

Applications

1. Pharmaceutical Research:

   • 4-Hydroxybenzyl alcohol is a biologically active compound known for its antioxidant and anti-inflammatory properties.
   • It serves as a model compound for studying phenolic antioxidants and their role in preventing oxidative stress.
   • It is found in natural sources, including olives, and is studied for its cardioprotective and neuroprotective effects.

2. Chemical Synthesis:

   • It is a precursor in the synthesis of various fine chemicals, including polymers, agrochemicals, and fragrances.
   • The hydroxyl group on the aromatic ring provides reactivity for substitution and coupling reactions.

3. Biomimetic Studies:

   • 4-Hydroxybenzyl alcohol is a structural analog of tyrosol, a naturally occurring antioxidant in olive oil. It is used in research focused on mimicking the beneficial properties of Mediterranean diets.

4. Material Science:

   • It is used in the preparation of phenolic resins and other polymeric materials.
   • It serves as a building block for advanced materials requiring phenolic functionality.

5. Antimicrobial Applications:

   • Due to its phenolic nature, it exhibits antimicrobial properties and is explored as an additive in formulations requiring biostatic effects.

Safety and Handling

4-Hydroxybenzyl alcohol is generally regarded as safe when handled under standard laboratory conditions, but caution should still be exercised.

Safety Precautions:

• Wear appropriate personal protective equipment (PPE) such as gloves, safety glasses, and lab coats.
• Work in a well-ventilated area or under a fume hood to avoid inhaling any dust or vapors.

Storage:

• Store in a cool, dry place, away from heat and direct sunlight.
• Keep the container tightly closed to prevent moisture uptake, as it may degrade over time.

First Aid:

• In case of skin contact: Wash thoroughly with soap and water.
• In case of eye contact: Rinse eyes with water for several minutes and seek medical attention if irritation persists.
• If ingested or inhaled: Seek immediate medical attention.

Environmental Impact

4-Hydroxybenzyl alcohol is not considered highly toxic to the environment, but care should be taken during disposal. Waste material should be handled according to local regulations to prevent contamination of water or soil.

Conclusion

4-Hydroxybenzyl alcohol is a versatile compound with applications spanning pharmaceuticals, material science, and organic synthesis. Its phenolic and alcohol functional groups make it reactive and adaptable for various industrial and research uses. Proper handling and storage ensure its stability and effectiveness, while its biological activities continue to make it a focus of scientific investigation.