2/22/2022
Solid phosgene, also known as triphosgene. The chemical name is bis (trichloromethyl) carbonate [Bis (trichloromethyl) Carbonate], abbreviated as BTC (structural formula shown in Figure 1) is an ideal substitute for phosgene. Phosgene and diphosgene are widely used in the synthesis of medicines, pesticides, organic intermediates, and polymer materials. However, due to their low safety, their usability is greatly limited. Phosgene and diphosgene have a low boiling point, are volatile and highly toxic, and have been banned or restricted in many countries.
Solid phosgene, also called triphosgene. The chemical name is bis(trichloromethyl) carbonate [bis(trichloromethyl)carbonate], abbreviated as BTC (structural formula, see Figure 1) and is an ideal substitute for phosgene. Phosgene and diphosgene are widely used in the synthesis of drugs, pesticides, organic intermediates and polymeric materials. However, due to its low security, its usability is very limited. Phosgene and diphosgene have a low boiling point, are volatile and very toxic and have been banned or restricted in many countries.
Triphosgene was first discovered in 1880. BTC is a white crystal with a pungent smell, with a relative molecular weight of 296.75, a melting point of 79-83°C, and a boiling point of 203-206°C. It is soluble in organic solvents such as ether, tetrahydrofuran, chloroform, and hexane. At room temperature, BTC has extremely low surface vapor pressure and high thermal stability. Even at distillation temperature, there is only a small amount of decomposition. Therefore, it is only treated as a general toxic substance in the industry. The chemical reactions it participates in are often very mild, with strong selectivity and high yield. At present, it is widely used in the synthesis of carbonate, chloroalkane, acid chloride, acid anhydride, urea, and poly heterocycles.
This paper mainly introduces and summarizes the preparation of triphosgene and its practical application in organic synthesis in recent years.
At present, the preparation methods of BTC are mainly batch method and continuous method; the mechanism is the chlorination reaction of dimethyl carbonate under photocatalysis.
2.1 Batch method
Dimethyl carbonate is dissolved in carbon tetrachloride, and under light, chlorine gas is passed continuously for more than 20 hours, and a free radical reaction occurs. After the reaction is over, carbon tetrachloride is distilled off, recovered, and used mechanically, and white crystal BTC can be obtained with a yield of over 95%.
2.2 Continuous method
The continuous method is based on two reactions, and three products of BTC, dimethyl carbonate and hydrochloric acid can be obtained according to the needs, which is an ideal process for producing BTC.
Triphosgene can undergo a phosgenation reaction with a nucleophile at a lower temperature; one molecule of triphosgene is equivalent to three molecules of phosgene, and it has many applications in fine organic synthesis.
3.1 Reaction of BTC with hydroxyl compounds
3.1.1 BTC can react with different hydroxyl compounds to obtain chloroformate products
3.1.2 The formed chloroformate intermediate can be combined with excess hydroxyl compound to obtain the carbonate product
3.1.3 Triphosgene can also react with vicinal diols to form cyclic carbonates, which is equivalent to the protection of hydroxyl functional groups
3.1.4 Triphosgene is also a good chlorination reagent, which can carry out chlorination reactions under mild conditions
3.1.5 Oxidation with alcohols to form aldehydes and ketones
3.2. Reaction of BTC with carboxylic acid compounds
3.2.1 Formation of acid chlorides
3.2.2 Anhydride formation
A molecule of carboxylic acid can react with 1/6 BTC in tetrahydrofuran and ethyl acetate to form acid anhydride.
3.3 Reaction of BTC with amino compounds
3.3.1 Formation of isocyanates with primary amines
Isocyanate compounds are an important class of polymer materials, such as polybenzylidene polyisocyanate, hexamethylene diisocyanate, etc.; isocyanate can form urea compounds with excess amines, which widely exist in pesticides and pharmaceutical intermediates.
3.3.2 BTC and secondary amines to generate acid chloride derivatives
In 1996, Kaufman used proline as a raw material and BTC-protected amino groups to prepare chiral amino acid precursors.
It can also generate urea intermediates with excess secondary amines, and then react with organometallic reagents to generate corresponding ketones.
3.4 BTC and bifunctional compounds to form heterocyclic compounds
3.4.1 Reaction of BTC with N, N bifunctional compounds
When there are primary amines, secondary amines, and carboxyl groups on the compound at the same time, BTC has higher selectivity for primary amines, and secondary amines and carboxyl groups do not need to be protected.
3.4.2 Reaction of BTC with N, O bifunctional compounds
3.5 BTC and N-formamide form isocyanide or imine
3.6 BTC and aldoxime or amide form nitrile compounds
3.7 FC reaction between BTC and aromatic compounds
references:
[1] Xing Fenglan. Research and application of a series of compounds synthesized by triphosgene instead of phosgene [J], Fine and Specialty Chemicals, 2006, 14(21): 11
[2] Wang Zhengping, Liu Tiancai. Synthesis and Application of Triphosgene [J], Progress in Chemical Industry, 2002, 21(3): 172
[3] Liao Lian'an, Zhao Shicai. Synthesis and application of triphosgene [J], Chemical Production and Technology, 1998, 4:33
[4] Lv Feng, Liu Yuting, Zou Jing, Zhang Dade, Yao Zuguang [J], Information Recording Materials, 2004, 5(3): 21
[5] Eekert, H., Forster, R. Angew. Chem., int. Ed, 1987, 922. [6] Jones, SS, et al. US 4321399(1990)
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