4,4'-Dimethoxytrityl chloride
[CAS# 40615-36-9]

Identification

• Classification: Biochemical >> Condensing agent
• Name: 4,4'-Dimethoxytrityl chloride
• Synonyms: 1,1'-(Chlorophenylmethylene)bis[4-methoxybenzene]; Di-p-anisylphenylmethyl chloride; DMT chloride; DMT-Cl
• Molecular Formula: C₂₁H₁₉ClO₂
• Molecular Weight: 338.83
• CAS Registry Number: 40615-36-9
• EC Number: 255-002-6
• SMILES: COC1=CC=C(C=C1)C(C2=CC=CC=C2)(C3=CC=C(C=C3)OC)Cl

Properties

• Density: 1.2±0.1 g/cm³, Calc.^*
• Melting point: 119-123 °C
• Index of Refraction: 1.584, Calc.^*
• Boiling Point: 463.1±45.0 °C (760 mmHg), Calc.^*
• Flash Point: 155.6±23.9 °C, Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS05;GHS07;GHS09 Danger
• Risk Statements: H314-H315-H317-H318-H319-H335-H411
• Safety Statements: P260-P261-P264-P264+P265-P271-P272-P273-P280-P301+P330+P331-P302+P352-P302+P361+P354-P304+P340-P305+P351+P338-P305+P354+P338-P316-P317-P319-P321-P332+P317-P333+P317-P337+P317-P362+P364-P363-P391-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Chronic hazardous to the aquatic environment	Aquatic Chronic	2	H411
Skin sensitization	Skin Sens.	1	H317
Serious eye damage	Eye Dam.	1	H318
Specific target organ toxicity - single exposure	STOT SE	3	H335
Skin corrosion	Skin Corr.	1	H314
Skin irritation	Skin Irrit.	2	H315
Eye irritation	Eye Irrit.	2	H319
Skin corrosion	Skin Corr.	1B	H314

Discovery and Applications

4,4'-Dimethoxytrityl chloride is a prominent chemical compound in the field of organic chemistry, particularly known for its applications in nucleic acid synthesis and peptide chemistry. This compound is a derivative of trityl chloride, which has been extensively utilized for protecting functional groups during synthetic procedures. The discovery of 4,4'-dimethoxytrityl chloride emerged from the need for more efficient protecting groups that could provide stability and enhance the overall yield in chemical reactions.

The synthesis of 4,4'-dimethoxytrityl chloride involves the reaction of trityl chloride with methanol in the presence of a suitable catalyst. This process introduces methoxy groups at the 4 and 4' positions of the trityl structure, resulting in a more sterically hindered and lipophilic compound. The presence of the methoxy groups not only improves the solubility of the compound but also enhances its protective capabilities during the synthesis of complex molecules.

4,4'-Dimethoxytrityl chloride is primarily employed as a protecting group for alcohols and amines in the synthesis of nucleosides and oligonucleotides. In these applications, the compound effectively shields reactive hydroxyl and amino groups from unwanted reactions during the synthesis process. The protective group can be easily removed under mild acidic conditions, restoring the original functional groups and enabling the subsequent steps of synthesis. This property is particularly valuable in the production of therapeutic oligonucleotides, which have gained significance in the fields of gene therapy and molecular biology.

In addition to its role in nucleic acid chemistry, 4,4'-dimethoxytrityl chloride has applications in peptide synthesis. Its ability to protect amino acids during solid-phase peptide synthesis allows for the construction of complex peptide sequences while minimizing side reactions. The use of this protecting group contributes to the efficiency and purity of the final peptide products, making it an essential tool in peptide-based drug development.

The versatility of 4,4'-dimethoxytrityl chloride extends to its applications in medicinal chemistry, where it is used in the synthesis of various bioactive compounds. The compound's protective properties enable the modification of lead compounds while preserving their biological activity, facilitating the development of novel therapeutics with enhanced efficacy and selectivity.

Recent advancements in the field have also explored the use of 4,4'-dimethoxytrityl chloride in combinatorial chemistry, where it aids in the rapid synthesis of diverse compound libraries. This approach has the potential to accelerate drug discovery processes by enabling the efficient generation of compounds with varied structures and properties.

In summary, 4,4'-dimethoxytrityl chloride is a vital compound with a rich history and numerous applications in organic synthesis, particularly in nucleic acid and peptide chemistry. Its discovery has significantly impacted synthetic methodologies, and its continued use underscores its importance in advancing research and innovation in pharmaceuticals and biotechnology.

References

2021. Synthesis of atom-specific nucleobase and ribose labeled uridine phosphoramidite for NMR analysis of large RNAs. Monatshefte für Chemie - Chemical Monthly, 152(12).
DOI: 10.1007/s00706-021-02851-2

2019. Efficient access to N-trifluoroacetylated 2'-amino-2'-deoxyadenosine phosphoramidite for RNA solid-phase synthesis. Monatshefte für Chemie - Chemical Monthly, 150(5).
DOI: 10.1007/s00706-019-02390-x

2019. Practical synthesis of N-(di-n-butylamino)methylene-protected 2-aminopurine riboside phosphoramidite for RNA solid-phase synthesis. Monatshefte für Chemie - Chemical Monthly, 150(10).
DOI: 10.1007/s00706-019-02502-7