[650-51-1] · C2Cl3NaO2 · Sodium Trichloroacetate · (MW 185.36)
(generation of the trichloromethyl anion and dichlorocarbene)
Physical Data: mp >300 °C.
Solubility: sol DME, diglyme.
Preparative Method: a methanol solution of Trichloroacetic Acid is neutralized with freshly prepared Sodium Methoxide to the phenolphthalein end point while keeping the temperature below 20 °C. The methanol is removed on the rotary evaporator at 20 °C. The salt is then dried in a vacuum oven at 50 °C for 20 h. The yield is nearly quantitative.1
Handling, Storage, and Precautions: is an irritant and is hygroscopic.
It was discovered that dichlorocarbene could be generated under essentially neutral conditions by heating a solution of sodium trichloroacetate. If this was done in the presence of an alkene, the corresponding dichlorocyclopropane was obtained (eqs 1 and 2). Cyclohexene and cycloheptatriene yielded the cyclopropyl derivatives in 65% and 47% yield, respectively.2
This was found to be the preferred method for the cyclopropanation of Trichloroethylene (eq 3). Although the yield was modest (22%), this was counterbalanced by the overall simplicity of the method.3 This yield was later improved to 47% by reducing the amount of 1,1-Dimethoxyethane (DME) used in the reaction by one half. The reduction in the amount of DME slowed the decomposition of the salt and cut down on the byproducts produced from the reaction of DME with dichlorocarbene. Hundreds of grams of the cyclopropane can be prepared in this way.4
Another modification in the way the reaction can be run is to use a combination of tetrachloroethylene, which is very unreactive,5 and DME. By using a 10:2.5 ratio of tetrachloroethylene:DME, the entire amount of the salt could be added at the start rather than in portions. In this solvent mixture, only a portion of the salt dissolves. This helps control the rate of CO2 evolution and hence the rate of carbene formation. Under these conditions, the yield of the cis-biscyclopropyl derivative of 1,5-cyclooctadiene (eq 4) rose to 62%. A small amount of the trans-bis-adduct was also formed, but was easily removed by recrystallization. If the solvent was tetrachloroethylene alone, none of the desired product was formed.6
Allene reacts with dichlorocarbene generated from the salt to afford the methylenecyclopropane derivative (eq 5).7
In an attempted cyclopropanation of Bis(trimethylsilyl)acetylene with sodium trichloroacetate (eq 6), the cyclobutenone was produced instead of the cyclopropane. The reaction with Phenyl(trichloromethyl)mercury resulted in ill-defined material.8
An effort to prepare diaziridines from azodicarboxylates and dichlorocarbene was thwarted by a rearrangement. The reaction of Diethyl Azodicarboxylate with sodium trichloroacetate in refluxing DME (eq 7) produced the rearranged compound in 69% yield. The same reaction with PhHgCCl2Br as the carbene precursor provided the same compound in 87% yield.9
The use of phase transfer conditions can provide an effective set of reaction conditions in some cyclopropanation reactions, with tetraheptylammonium bromide and Aliquat® 336 being the most effective.10 In addition, crown ethers were found to accelerate the loss of CO2, but at the same time result in somewhat lower yields.11
Dichlorocarbene has been shown to be capable of inserting into a C-H bond of alkyl-substituted aromatics. Thus the reaction of cumene with sodium trichloroacetate (eq 8) in refluxing DME resulted in a 33% yield of b,b-dichloro-t-butylbenzene. Only a 0.5% yield of insertion product was obtained if the dichlorocarbene was formed using Chloroform/Potassium t-Butoxide.12 Prior to this, halocarbenes were not known to attack C-H bonds.
The insertion into Si-H is also possible. Treatment of Triethylsilane with sodium trichloroacetate affords the dichloromethylsilane (eq 9) in 32% yield.13 The insertion of dichlorocarbene into the Si-H bond occurs with retention of configuration at silicon. The reaction of (+)-a-naphthylphenylmethylsilane (eq 10) with sodium trichloroacetate in the presence of 18-Crown-6 produces (+)-a-naphthylphenylmethyldichloromethylsilane in 70% yield.14
The reaction of the tricyclic anhydride with sodium trichloroacetate did not result in any dichlorocyclopropane formation. Instead, the product from the addition of the trichloromethyl anion to the anhydride was produced (eq 11).1 The reaction of aldehydes (eq 12) and acid chlorides (eq 13) under these conditions also affords products resulting from the reaction of the trichloromethyl anion.15 The yields for these later two processes were not as good as for the reaction with the anhydride. The presence of the anhydride was found to accelerate the decomposition of the salt.
Sodium trichloroacetate has been employed in the syntheses of trimethylsilyl trichloroacetate16 and t-butyldimethylsilyl trichloroacetate.17 The trimethylsilyl derivative was prepared from the salt and the silyl chloride in 83% yield in benzene using 18-crown-6 as the catalyst (eq 14). The t-butyldimethylsilyl compound was formed in 83% yield in an uncatalyzed reaction between the salt and the silyl chloride in THF (eq 15). These two reagents have found use for the introduction of silyl-protecting groups.17,18 The trimethylsilyl trichloroacetate has also found application in a simple procedure for the preparation of Mosher's acid.16
Dichlorocarbene has been found to mediate carbon-carbon bond formation in the coupling of benzazoles to bis-benzazoles. The yields of the bis-benzazoles were identical using either the sodium trichloroacetate method (eq 16) or the Chloroform/Sodium Hydroxide/phase transfer method to generate dichlorocarbene.19
In a ring-expansion route for the preparation of (2,4)pyridinophanes, the bicyclic pyrrole was heated with sodium trichloroacetate in DME (eq 17) to provide the pyridinophane in 28% yield. An analogous reaction with phenyl(bromodichloromethyl)mercury as the source of dichlorocarbene produced the same compound but only in 20% yield.20
Michael J. Taschner
The University of Akron, OH, USA