Trichloromethyl anion

When trichloroacetic acid is used to protonate an enamine (17,17a), the salt has only limited stability. The trichloroacetate anion undergoes decarboxylation and the trichloromethyl anion which is generated adds to the iminium salt, giving an a-amino trichloromethyl derivative (8). 

Trichloroacetic acid behaves somewhat similarly in that protonation of the enamine occurs l7J7d). Subsequent decarboxylation of the trichloro-acetate gives trichloromethyl anion, which adds to the iminium cation to give the trichloromethyl amine derivative. Thus the enamine (113) undergoes reaction with trichloroacetic acid to give N-[l-(trichloromethyl)cyclo-hexyl]-morpholine (8). The latter compound undergoes rearrangement on... 

A method that provides an alternative route to dichlorocarbene is the decarboxylation of trichloroacetic acid.161 The decarboxylation generates the trichloromethyl anion, which decomposes to the carbene. Treatment of alkyl trichloroacetates with an alkoxide also generates dichlorocarbene. 

The change in selectivity on changing the catalyst is ascribed to lower lipophilicity and greater hydration of the tight Q+ CCI3 ion pair, which reduces the activity of the trichloromethyl anion, allowing more time for decomposition to the carbene. The effect of catalyst structure may be summarized as follows [47] ... 

From Chapter 7 it is apparent that the trichloromethyl anion is formed under basic conditions from chloroform, as a precursor of the carbene. The anion can also react with Jt-deficient alkenes (see Section 7.3) and participate in nucleophilic substitution reactions, e.g. 1,1-diacyloxy compounds are converted into 1,1,1-trichloroalkan-2-ols [58] (Scheme 6.35). Similarly, benzyl bromides are converted into (2-bromoethynyl)arenes via an initial nucleophilic displacement followed by elimination of hydrogen bromide [59] (Scheme 6.35). 

As indicated in Chapter 1, the hydroxide ion is not readily transported into the organic phase, particularly when the benzyltriethylammonium ion is employed as the catalytic cation. Hence, the reaction of chloroform with the hydroxide ion must occur by an interfacial mechanism. The interfacial reaction initially produces the trichloromethyl anion, which immediately forms an effective ion-pair with the benzyltriethylammonium cation. Diffusion of the ion-pair into the bulk of the organic phase occurs, followed by a slow decomposition of the trichloromethyl anion... 

That the formation of the trichloromethyl anion is an interfacial reaction is evident from the high stirring rate required to maintain reproducibly high yields (see Chapter l). In many reported reactions, chloroform is used as the organic solvent, whereas in other examples it is used in a fourfold excess over the reactive substrate in dichloromethane. Benzene has also been used as the co-solvent but it reduces the rate of the reaction, probably because it is a poorer solvent for benzyltriethylammonium salts. 

With the exception of the parent compounds, where the Michael adducts are isolated, acrylic esters [see, e.g. 6,7,31,105,111 ] and nitriles [6,7], and vinyl ketones [26, 113, 115] generally yield the cyclopropanes (Table 7.6) under the standard Makosza conditions with chloroform. Mesityl oxide produces a trichlorocyclopropy-lpropyne in low yield (10%) [7]. When there is no substituent, other than the electron-withdrawing group at the a-position of the alkene, further reaction occurs with the trichloromethyl anion to produce spiro systems (35-48%) (Scheme 7.12) [7, 31]. Under analogous conditions, similar spiro systems are formed with a,p-unsaturated steroidal ketones [39]. Generally, bromoform produces cyclo adducts with all alkenes. Vinyl sulphones are converted into the dichlorocyclopropane derivatives either directly or via the base-catalysed cyclization of intermediate trichloromethyl deriva-... 

A combined -cyclodextrin quatemary ammonium salt catalyst promotes the addition of the trichloromethyl anion to aromatic aldehydes and enhances the yield of the a-hydroxy acid [7],... 

Conjugated ketones and esters generally react with chloroform under basic conditions by Michael-type addition of the trichloromethyl anion to the C=C bond or by insertion of dichlorocarbene into the C=C bond, depending on the substitution pattern of the conjugated system (see Sections 6.4 and 7.3). The corresponding reaction with bromoform under basic conditions produces 1,1-dibromocyclopropanes. 

In reactions which have some analogy with the interaction of dichloro-carbene/trichloromethyl anions with ketones, 2-dichloromethyloxazolines yield chloro-oxiranes and a-chlorocarbonyl compounds (Scheme 7.18). The formation of the oxiranes is favoured with aldehydes and lower homologue ketones, whereas cyclic ketones and aryl ketones are converted preferentially into the a-chloro carbonyl derivatives [18]. 

Reaction of the azophosphoranes (Scheme 7.32) with dichlorocarbene follows an interesting pathway to produce l-aryl-5-chloropyrazole-3-carboxylic esters. The initial displacement of the phosphine (probably as the oxide) has been confirmed by the isolation of the 3,3-dichloropropenic ester under mild conditions. Subsequent conversion into the pyrazole appears to involve reaction with a trichloromethyl anion followed by attack by a second dichlorocarbene, although evidence for the mechanism of these steps is circumstantial [40],... 

Attempts to produce chiral cyanhydrins under phase-transfer catalytic conditions (3.3.9) using ephedrinium or cinchoninium catalysts has been singularly unsuccessful [21,22]. Optical purities varying from 0 to 60% have been recorded [22], but verification of the reproducibility of the higher values is needed. Similarly, nucleophilic attack on a carbonyl group by the trichloromethyl anion under phase-transfer catalytic conditions (see Section 7.4) in the presence of benzylquininium chloride produces a chiral product, but only with an enantiomeric excess of 5.7% [23]. The veracity of this observation has also been questioned [24],... 

The facile elimination of the trichloromethyl anion favours the formation of (LXXXIX) and provides the driving force for triazine formation. The alternative possible initial formation of (XCI) seems less likely, since cyclohexylamine and ethyl trichloroacetate give cyclo-hexyltrichloroacetamide (CaHn-NH-CO-CCls) and not the cyclo-hexylurethan 600). 

Thermolysis of 59 in chloroform (17) led to formation of carbonyl ylide 64, subsequent proton abstraction from chloroform (p fa = 24.1), and recombination with the trichloromethyl anion gave acetal 65. The intermediacy of radicals was discounted since conducting the reaction in neat BuaSnH did not change the product distribution. 

Generation of dichlorocarbene and its addition to an alkene in a two-phase system proceeds somewhat differently. Here a solution of an alkene in chloroform forms the organic phase the other is concentrated aqueous NaOH. The first step, deprotonation of chloroform, occurs at the phase boundary then the trichloromethyl anion formed at the phase boundary enters the organic phase in the form of ion pairs with Q+. Inside the organic phase the anions dissociate reversibly to dichlorocarbene and Q+C1 exchanges anions at the phase boundary so that Cl passes into the aqueous phase and another trichloromethyl anion into the organic phase. Anions are transferred to the organic phase not from the aqueous phase but from the phase boundary. Reference 5 contains additional details. 

Dichlorocarbene is the reactive intermediate formed by the reaction of alkali on chloroform, and typically it adds to olefins to give 1,1-dichlorocyclo-propanes. The PTC procedure for the generation of dichlorocarbene is particularly useful and is illustrated by its reaction with cyclohexene to form (38) (Expt 7.15). The mechanism is formulated below and probably involves the reaction of the quaternary ammonium hydroxide with chloroform at the phase boundary, and dissolution into the organic phase of the quaternary ammonium derivative of the trichloromethyl anion (41). This species breaks down to form dichlorocarbene and the quaternary ammonium chloride. The latter returns to the aqueous phase to maintain the cycle of events, while the dichlorocarbene reacts rapidly with the cyclohexene in the organic phase. 

The two intermediates probably arise in the later stages of the reaction when the thioalkoxide concentration is low. The presence of these intermediates is evidence of the intermediate formation of the trichloromethyl anion, in reactions of the following kind. 

However, reaction of acyclic dienamines with hydrazoic acid gives a mixture of products derived by 1,2-, 1,4- and 3,4 + 1,2-addition of HN3 to the diene system. In this case C-protonation is followed immediately by addition of the strongly nucleophilic azide anion, so that equilibrium of the C-protonated enamines cannot occur3c. Treatment of the morpholine dienamine of isophorone with trichloroacetic acid in boiling benzene resulted in decarboxylation and the 1,4-addition of a proton and the trichloromethyl anion. Basic hydrolysis of the adduct gave dienoic acid 54 (Scheme 4). 

The thermal decomposition of sodium trichloroacetate initially gives the trichloromethyl anion (Eq. 1). In the presence of a proton-donating solvent (or moisture) this anion gives chloroform in the absence of these reagents the anion decomposes by loss of chloride ion to give dichlorocarbene (Eq. 2). 

Ordinarily water must be scrupulously excluded from carbene-generating reactions. Both the intermediate trichloromethyl anion (3) and dichlorocarbene (4) react with water. But in the presence of a phase transfer... 

Carbon tetrachloride undergoes stepwise reduction at mercury in DMF containing TEABr [45]. Several groups of workers [46-52] have electrogenerated the shortlived trichloromethyl anion, which can react with acrylonitrile, ethyl acrylate, diethyl fumarate, alkyl monohalides, and a variety of aldehydes and ketones. De Angelis and coworkers [53] have used dichlorocarbene, generated via reduction of carbon tetra-... 

The first example for the insertion of an electrogenerated dichlorocarbene into substituted indoles was described by F. De Angelis and co-workers. The dichlorocarbene was generated by reduction of CCU, followed by fragmentation of the resulting trichloromethyl anion. Under these conditions, 2,3-dimethylindole was converted to 3-chloro-2,4-dimethylquinoline and 3-(dichloromethyl)-2,3-dimethyl-3/-/-indole in moderate yield. The study revealed that the reaction mechanism and product formation are determined by the acidity of the solvent. 

Trichhromethylation of anhydrides. When the salt is decomposed in 1,2-di-mcthoxyethane in the presence of an olefinic anhydride, reaction occurs exclusively at a carbonyl group of the anhydride, apparently by the trichloromethyl anion precursor of the carbene, to give the trichloromethyl addition product. Yields are erratic, ranging from 80 to 8%. 

Carbenes bear a resemblance to carbocations in that there is an empty p orbital that can behave as an electron sink. However, a full orbital that can serve as an electron source is on the same atom. Trichloromethyl anion loses chloride, forming the reactive dichlorocarbene, a neutral, electron-deficient, electrophilic intermediate. Stabilization in dichlorocarbene results from the interaction of the full lone pair orbitals of chlorine with the empty p orbital of the carbene (Fig. 8.11). If the donors on the carbene are good enough, the carbene becomes nucleophilic. With few exceptions, carbenes react stereospecifically with double bonds to produce three-membered rings. 

The reaction is carried out under neutral conditions, therefore base-sensitive compounds are well tolerated. According to the standard procedure, a mixture of alkene and sodium trichloroacetate was heated in 1,2-dimethoxyethane, at ca. 80°C. In the case of alkenes of low reactivity, a large excess (ca. 10 mol) of sodium trichloroacetate was required. A useful modification consists of refluxing the components in inexpensive chloroform in the presence of catalytic amounts of tetraalkylammonium salt. ° The trichloromethyl anion would be expected to participate but has been inferred in one experiment only. ... 

Attempted 1,4-cycloaddition of dichlorocarbene with 1,3-diphenylisobenzofuran was unsuccessful (Houben-Weyl, Vol.E19b, pi562). The formation of 8,8-dichloro-2-(2-phenylethyl)-2,3-dihydro-l,3-methano-l//-isoindole-l-carbonit ile (31) by the reaction of chloroform with isoindole derivative 30 under phase-transfer catalysis conditions has probably been misinterpreted as 1,4-addition of dichlorocarbene.This reaction may involve the Michael addition of trichloromethyl anion to isoindole followed by the cyclization of the adduct. 

The reactivity of alkenes toward dichlorocarbene also decreases if there is a halogen in an allylic position. In this case side reactions, such as alkylation of trichloromethyl anion, halide exchange in the case of allylic bromides etc., take place. Although the yields of the products from these side reactions are low, they impede the isolation of the desired product, e.g. formation of 3, 4, and... 

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