Bis trichloromethyl Carbonate

Hiroshi Sano Gunma University, Kiryu, Japan 

Solubility sol methanol, ethanol, benzene, diethyl ether, hexane, THF, ethyl acetate dec slowly in cold water. 

Handling, Storage, and Precautions the reagent is somewhat moisture sensitive, but scrupulously anhydrous conditions are not necessary. Rapid handling of the reagent in open air, in the absence of a glove bag or dry box, is usually satisfactory. This reagent should only be handled in a fume hood. 

Chloroformylation. The use of triphosgene in the formation of chloroformates with both hydroxy compounds (eq 4) and substituted amines (eq 5) has been reported.  

Dehydration.. Synthesis of isocyanides from formamides (eq 6) is the only example of a dehydration reaction reported for triphosgene to date.  

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Triphosgene (bis(trichloromethyl)carbonate) has been used to deoxochlorinate [VOCh] - to [VClfi] - and [V02Cl2] to [VOCh] [6]. In both these cases the deox-ochlorination was accompanied by spontaneous reduction of the initial products (Scheme 6.1-2). 

Bis(2-diisopropylaminoethyl) Disulfide Bis(2-diisopropylaminoethyl) Sulfide Bis(2-fluoroethyl) 2-Chloroethylamine Bis(2-fluoroethyl)methylamine Bis(2-hydroxyethyl) Sulfide Bis(2-hydroxyethyl) Thioether Bis(2-hydroxyethyl)amine Bis(2-hydroxyethyl)methylamine Bis(2-propenyl) Sulfide Bis(bromomethyl) Ether Bis(chloromethyl) Ether Bis(cyclohexyl)carbodiimide Bis(ethenyl)sulfone Bis(trichloromethyl) Carbonate Bis(/3-bromoethyl) Sulfide Bis(/3-chloroethyl)ethylamine Bis(/3-Chloroethyl)methylamine Bis(/3-chloroethylthio)ethane Bis(/3-mercaptoethyl) Sulfide... 

Regioselective protection of the pentaol 230 with bis-trichloromethyl carbonate and subsequent acetic anhydride treatment affords the C-10 acetoxy C-l, C-2 carbonate compound 231 in good yield. Deprotection of the acetonide function and regioselective silylation of the C-7 hydroxyl group, followed by... 

Synthesis of the tricyclic [l,2,4]triazolo[l,5-c][l,3]benzoxazine 290 was described by an Italian group <1994FA89, 1995JME2196>. These authors reacted the triazolylphenole 289 with bis-trichloromethyl carbonate to obtain the tricyclic product 290 in poor to good yield. 

WH Daly, D Poche. The preparation of V-carboxyanhydridcs of a-amino acids using bis(trichloromethyl)carbonate. Tetrahedron Lett 29, 5894, 1988. 

More recent developments favor bis(trichloromethyl)-carbonate, which is produced by exhaustive photochlorination of dimethyl carbonate. 

Scheme 36 SPPS of N-Alkylated Peptides by the Bis(trichloromethyl) Carbonate Method,3°l...

A slightly modified version of the bis(trichloromethyl) carbonate method 30 has been used for the total SPPS of cyclosporin O 29 (Scheme 1) and omphalotin A 40 (Scheme 37). Since in this case an acid sensitive trityl resin was used, excess DIPEA was added to the resin. 

Bis(trichloromethyl) Carbonate Mediated Coupling General Procedure 1301... 

Fmoc-peptide-resin was deprotected with 20% piperidine/DMF (2 min+8 min). After washing, the resin was treated with dry THF (1 mL) for 15 min. Meanwhile, the Fmoc amino acid (3.5 equiv) was added to a 68 mM soln of bis(trichloromethyl) carbonate in dry THF [1.15 mM of bis(trichloromethyl) carbonate]. 2,4,6-Collidine (10 equiv) was added to the clear soln, upon which a precipitate of collidinium chloride formed. DIPEA (8 equiv) was added to the resin, immediately followed by addition of the suspension. The mixture was shaken for the times given in Scheme 39, filtered, and washed. 

L. Cotarca, P. Delogu, A. Nardelli, V Sunjic, Bis(trichloromethyl) Carbonate in Organic Synthesis, Synthesis 1996, 553-576. 

Other syntheses of this type are exemplified by the conversion of 126 to 127 by treatment with sodium sulfide (Scheme 79) <2004T4361, CHEC-III(11.16.6.1.2)711 >, the synthesis of the tricyclic [l,2,4]triazolo[l,5-z][l,3]benzox-azine 129 by reaction of the triazolylphenol 128 with bis-trichloromethyl carbonate (Scheme 80) <1995JME2196, CHEC-III(11.16.6.1)710>, and the preparation of indolo[2,l-z]benzo[l,2,4]triazine derivatives 131 by diazotization of 2-amino- 1-aryltetrahydroindoles 130 followed by an intramolecular coupling of the diazonium group with the aryl moiety (Scheme 81) <2003H2519, CHEC-III(11.14.8.4)638>. 

Scheme 10 Reaction of an Amino Acid with Bis(trichloromethyl) Carbonate (Triphosgene) To Produce N-Carboxyanhydrides...

The reversibility of the decomposition of Diphosgene into carbon tetrachloride and carbon dioxide is still a controversial topic. However, the production of phosgene by reaction of carbon tetrachloride and carbon dioxide over catalysts such as Lewis acids was recently claimed in Russian patents (Ref. 32). The reaction is assumed to proceed through the formation of trichloromethyl chloroformate or bis(trichloromethyl) carbonate. 

Kricheldorf, H. R. Lubbers, D., Polymers of carbonic acid, 1. Synthesis of thermotropic aromatic polycarbonates by means of bis(trichloromethyl) carbonate, Makromol. Chem. Rapid Commun. 1989, 10, 383-386. 

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