Trichloromethyl chloroformate activator

Trichloromethyl chloroformate (diphosgene) is used as a safe substitute for highly toxic phosgene gas. The latter is generated in situ by addition of catalytic amounts of tertiary amines or amides, or active carbon. Diphosgene also disproportionates to 2 equivalents of phosgene on heating above 250°C. 

Figure 6. Block drawing of the pilot installation for the production of trichloromethyl chloroformate by exhaustive photochlorination [39] 1 Dryer for gaseous Cl2 (H2S04 cone.). 2 Safety tank. 3 Thermoregulated immersion-type photochemical reactor. 4 Raschig column. 5 Cl2 detection system (1,2,4-trichlorobenzene). 6 Neutralization tank (20% NaOH). 7 Reservoir of 20% NaOH. 8 Buffer to atmospheric pressure (20% NaOH). 9 Active carbon filter. 10 Reservoir of crude trichloromethyl chloroformate. 11 Buffer to normal atmosphere via CaCl2 filter and direct entry for trichloromethyl chloroformate to be distilled. 12 Distillation flask with Vigreux column. 13 Exit to vacuum pump. 14 Solid NaOH filter before pump. 15 Cooling water alarm linked to power supply of the light source. 16 Medium pressure mercury arc. 17 Heater for distillation apparatus. 18 Magnetic stirrers. /T thermometer /P manometer.

Despite this they should be considered as possible alternatives in cases where more familiar methods fail. Amongst this group of activators are p-toluenesulfonyl chloride, tiifluoromethanesulfonic anhy-dride,silver tetrafluoroborate, molybdenum oxide, phosphorous pentoxide, trichloromethyl chloroformate, 2-fluoro-l-methylpyridiniumsulfonate, chlorosulfonyl isocyanate, antimony penta-chloride (for which an X-ray structure of the DMSO-SbCb conqilex was obtained) and phenyl dichlo-rophosphate. ... 

This decomposition takes place also at ordinary temperatures when trichloromethyl chloroformate comes into contact with substances having a porous structure such as activated carbon, or with iron oxide, etc. 

Sigurdsson, S.T., Seeger, B., Kutzke, U. and Eckstein, F. (1996) A mild and simple method for the preparation of isocyanates from aliphatic amines using trichloromethyl chloroformate. Synthesis of an isocyanate containing an activated disulfide. The Journal of Organic Chemistry, 61, 3883-3884. 

In order to avoid the need for DCC, a number of activated derivatives of IV-hydroxysuccinimide itself have been developed which react directly with, for example, an oi-amino acid to provide the required activated oi-amino acid esters. These include the commercially available carbonate (1), a stable crystalline solid obtained from HOSu and Trichloromethyl Chloroformate or from 0-trimethylsilyloxysuccinimide and Phosgene and the related phosphate (2) derived from HOSu and Diphenyl Phosphorochlo-ridate under Schotten-Baumann conditions. Another alternative (also commercially available) is the oxalate (3), formed from HOSu and Oxalyl Chloride In general, these intermediates react rapidly with an iV -protected a-amino acid, usually in the presence of a mild base such as pyridine, to provide excellent yields of the required hydroxysuccinimide esters, generally with less racemization than is sometimes associated with the HOSu-DCC method. It is also possible to cany out the entire process of peptide synthesis in one pot using these reagents. 

The metabolism of carbon tetrachloride proceeds via cytochrome P-450-dependent dehalogenation (Sipes et al. 1977). The first step involves cleavage of one carbon-chlorine bond to yield Cl- and a trichloromethyl free radical, which is then oxidized to the unstable intermediate trichloromethanol, the precursor of phosgene. Hydrolytic dechlorination of phosgene yields C02 and HC1 (Shah et al. 1979). Although there are similarities in the metabolism of chloroform and carbon tetrachloride, metabolic activation of chloroform produces primarily phosgene, whereas the level of phosgene production from... 

The lack of trichloromethyl anion adducts to acrylates in these processes is possibly due to relatively tight, poorly lipophilic ion pairs Me4N CCI3 which cannot penetrate the organic phase thus, they reside in the interfacial region where the hydrated trichloromethyl anions have low activity. Consequently, dichlorocarbene reacts with acrylates to form 1,1-dichlorocy-clopropanes 2. ( )-A -tert-Butyl but-2-enamide forms the cyclopropane 3 on reaction with dichlorocarbene, generated from chloroform/base/phase-transfer catalyst, with tetramethylam-monium chloride as the catalyst. ... 

Dechlorothiolation. Activated trichloromethyl groups (e.g., in RCOCCI3) are converted to the benzenethiomethyl residues using PhSH-PhSNa. Both substitution and hydrodechlorination occur on such treatment. However, chloroform and a,a,ct-trichloro-toluene do not react in the same manner. 

There are many strategies for the synthesis of carbonates [19,203] (Fig. 11) on polymeric supports. Some of the most common ones are the activation of an alcohol via addition of fois-trichloromethyl carbonate (BTC) and base [204], the activation of alcohols via for example carbonyl diimidazole and subsequent transformation with alcohols [19] or the direct conversion of resin-bound alcohols into carbonates via reaction with chloroformates. 

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