Application background and overview of triphosgene
Phosgene is also known as solid phosgene. The chemical name of triphosgene is bis (trichloromethyl) carbonic acid, its English name is Bis (Triehloromethyl) Carbonate (BTC for short), its common name is Triphosgene, and its molecular formula is CO (OCCl3)2. Triphosgene is a white crystal with an odor similar to phosgene. The relative molecular mass is 296.75, the melting point is 81 ℃ ~ 83 ℃, the boiling point is 203 ℃ ~ 206 ℃, the solid density is 1.78 g/cm3, and the melt density is 1.629 g/cm3 , soluble in organic solvents such as ether, tetrahydrofuran, benzene, ethane, and chloroform. Its physical properties were reported in 1887, but its crystal structure was not reported until 1971.
Triphosgene is a compound with asphyxiating toxicity. Is a potentially asphyxiating poison. Hydrolysis is very slow and can be accelerated by heating or adding alkali. Soluble in organic solvents such as toluene, chlorobenzene, alkyl halides, kerosene, etc., miscible with phosgene, and also soluble in mustard gas, chloropicrin, and acidic fumes such as silicon tetrachloride, tin tetrachloride, and titanium tetrachloride. in the agent. It can be released with smoke screens and is easily adsorbed by porous substances. Activated carbon has high adsorption efficiency, and gas masks can effectively protect it. Triphosgene is a widely used chemical raw material and can be used to prepare chemical products such as chloroformate and isocyanate.
However, phosgene is a highly toxic gas that is difficult to use, transport and store, and is difficult to accurately measure in applications. Some of the side reactions produced also bring great inconvenience to laboratories or small-scale use. Triphosgene is a stable solid crystalline compound. Its use, transportation and storage are safer than phosgene, and it can be measured accurately, which can reduce the occurrence of side reactions. As a substitute for the highly toxic phosgene and diphosgene in synthesis, triphosgene not only has low toxicity, is safe and convenient to use, but also has mild reaction conditions, good selectivity and high yield. Due to the chemical properties of solid phosgene, it has a wide range of applications. Triphosgene can replace phosgene and is used in chemical production of various scales, and its application prospects are very broad.
The application reaction mechanism of triphosgene
Under the action of nucleophiles (Nu) such as triethylamine, pyridine, diisopropylethylamine and dimethylformamide, triphosgene reacts with the substrate as follows:
It can be seen from the above reaction formula that 1 mol triphosgene is equivalent to 3 mol phosgene, and corresponding salts are formed at the same time. 1 molecule of triphosgene can generate 3 molecules of active intermediate (ClCONu+Cl-), which can react with various nucleophiles under mild conditions. It is based on this mechanism that triphosgene can react with alcohols, aldehydes, amines, amides, carboxylic acids, phenols, hydroxylamine and other compounds. The reaction types that can replace phosgene and diphosgene include chloromethylation and urealysis. , carbonation, isocyanation, chlorination, isonitrilation, cyclization reaction, alcohol oxidation, etc., and are widely used in the synthesis and production of medicines, pesticides, dyes, pigments and various polymer materials.
Applications of triphosgene
Application of triphosgene 1. Synthesis of isocyanate
The carbonylation reaction between phosgene and primary amines can produce various isocyanates. However, because phosgene is difficult to accurately measure, side reactions often occur. Triphosgene is a solid and can be measured accurately, and using triphosgene instead of phosgene greatly improves its safety, so it can safely replace phosgene. The reaction between triphosgene and amine compounds is a widely used field. This reaction is highly selective. Some calcium carbonate functional groups do not require protection and can directly generate isocyanate, urea and other compounds.
The carbonylation reaction between triphosgene and various primary amines can synthesize various isocyanates. The reaction only needs to accurately control the ratio of triphosgene and amines to obtain the target product without the occurrence of by-products. For example: triphosgene reacts with 2,4-diaminodiphenylmethane to synthesize 2,4-dimethyldiisocyanate (TDI); triphosgene reacts with 4,4′-diaminodiphenylmethane to generate 4,4′- Diphenylmethane diisocyanate (MDI); triphosgene and hexamethylenediamine can generate sodium hexamethylene diisocyanate (HDI).
BTC can also perform cyclization and condensation reactions during the carbonylation reaction. In this type of reaction, triphosgene is widely used. It can be used not only to prepare N-carbonyl anhydride, but also to prepare various important heterocyclic compounds and cyclic carbonate compounds. The former can be used to prepare active amino acids and polypeptide compounds, and the latter can be used to prepare various pharmaceutical and pesticide intermediates.
Application of triphosgene 2. Synthesis of polycarbonate
The traditional process for synthesizing polycarbonate is to use phosgene and bisphenol A as raw materials and dichloromethane as the solvent. The current synthesis method of polycarbonate is to use acid diphenyl ester and monomer bisphenol for transesterification, which replaces the conventional phosgene synthesis route and achieves two green goals at the same time: first, no toxic and harmful raw materials are used; Second, because the reaction is carried out in a molten state, suspected carcinogens (methyl chloride) are not used as solvents.
For example: triphosgene and 1,4-hydroquinone can react to prepare thermally denatured polycarbonate; 4,4′-dihydroxybiphenyl, 4,4′-dihydroxydiphenyl ether, 4,4&r Fluorophenylboronic acid – dihydroxybenzophenone, bisphenol A and 4,4′-dihydroxydiphenylsulfone and other dihydric phenols can generate thermotropic liquid crystals in the presence of triphosgene.�Carbonate; bisphenol A polycarbonate copolymer can be produced by solution condensation polymerization of triphosgene and the O,O’-methylene bridged dimer of bisphenol A; using triphosgene and bisphenol A as monomers, Use interfacial polycondensation method to synthesize high molecular weight polycarbonate; triphosgene can also be used to prepare thermoplastic polycarbonate and polycarbonate-styrene-acrylonitrile terpolymers and other high molecular polymers, functional polymerized styrene wait.
Application of triphosgene 3. Synthesis of chloroformate
Using triphosgene and alcohol or secondary amine as raw materials, they react in the presence of solvent to generate chloroformate. Eckert used tertiary alcohols and functionalized amides as solvents to synthesize chloroformates in high yields. It first reacts with a nucleophile to form an unstable intermediate, which then reacts with a hydroxyl compound to form a chloroformate. Triphosgene chloroformylation reaction can be used in organic synthesis to prepare various important chemical intermediates. Such as: synthesis of β-lactam antibiotic precursors, synthesis of cationic lipid compounds, synthesis of active carbamates, etc.
Application of triphosgene 4. Synthesis of acid chlorides and acid anhydrides
Due to the high chlorine content in triphosgene molecules, it is a good chlorinating agent and can be used in chlorination reactions. The reaction of triphosgene and carboxylic acid can produce various acid chlorides and acid anhydrides, especially aromatic acid chlorides and acid anhydrides. Using triphosgene to synthesize acid chlorides and acid anhydrides has mild reaction, convenient post-processing, less pollution and high yield.
Applications of triphosgene 5. Synthetic medicines and pharmaceutical intermediates
Triphosgene can be used to replace phosgene and diphosgene in the synthesis of drugs and pharmaceutical intermediates. For example: triphosgene is used to replace trichloromethyl chloroformate and triphenylazepine to react with triphenylazepine to synthesize formamide benzene, which is used for the synthesis of antidepressant and analgesic drug carbamazepine; triphosgene is used with N-ethyloxypiperazine Reaction to synthesize N-ethyloxypiperazine acid chloride, which is used for the synthesis of oxypiperazine penicillin side chain intermediates; triphosgene is used to replace phosgene and trichloromethyl chloroformate interacts with anthranilamide for the antihypertensive drug quinine Synthesis of oxazolinediones.
Application of triphosgene 6. Synthetic pesticides
Triphosgene reacts with alcohol to prepare chloroformate, which can then be further reacted with the corresponding amine to prepare a series of carbamate pesticides. Triphosgene reacts with secondary amines to obtain aminoacyl chloride, which can then react with another molecule of amine to produce many urea herbicides, such as linuron. The corresponding acyl isocyanate can be prepared by reacting triphosgene with 2,6-difluorobenzamide, which can then be reacted with a suitable amine to prepare a series of benzoyl urea pesticides. Similarly, triphosgene and sulfonamide can also be used to prepare sulfonylurea herbicides.
In addition, triphosgene reacts with 1,2-bifunctional compounds such as 1,2-diamine, diol (alcohol), aminoalcohol, amino acid, aminoamide, o-aminophenol and catechol to form a five-membered heterogeneous compound. Cyclic compounds, which are important intermediates for many pesticides. Another example is the cyclization reaction of triphosgene and 2-amino-5-methoxyphenol to synthesize the natural product 6-methoxy-2,3-dihydrobenzothiazole with fungicidal activity.
Application preparation of triphosgene
The synthesis of BTC usually uses dimethyl carbonate to perform a thorough photochlorination reaction in carbon tetrachloride. The chemical reaction formula is as follows:
The reaction proceeds at a lower temperature, accompanied by the release of a large amount of heat, which requires cooling to transfer heat. Nuclear magnetic resonance studies show that the chlorination reaction proceeds in steps. As the degree of chlorination deepens, the chlorination reaction rate gradually slows down. This is due to the influence of steric hindrance, which makes -OCHCl2 more intense than -OCH2Cl. Difficult to further chlorine. Therefore, the temperature in the later stage of the reaction should be appropriately increased to increase the reactivity of free radicals, and the introduction speed of chlorine should be appropriately slowed down. From the overall process point of view, this will not only not reduce the reaction speed, but on the contrary, it can speed up the reaction process. .
