Dichlorocarbene, intermediate

Various synthetic routes to isocyanides have been reported since their identification over 100 years ago.8 Until now, the useful synthetic procedures all required a dehydration reaction8-11 Although the carbylamine reaction involving the dichlorocarbene intermediate is one of the early methods,8 it had not been preparatively useful until the innovation of phase-transfer catalysis (PTC).4 5... 

The most familiar, and most studied, example of 1,1-elimination occurs where no / -H atoms are available—the operation of factor (c) above—in the hydrolysis of haloforms, e.g. CHC13 (77), with strong bases. This involves an initial 1,1-elimination, probably via a two-step, i.e. 1,1-ElcB, pathway, to yield a dichlorocarbene intermediate (78) ... 

The case of p-hydroxy-y-alkenyl selenides merits further comments. The rearrangement efficiently takes place using the thallium(I) ethoxide method and the presence of an additional double bond in the reactant does not introduce a serious problem associated with unwanted reaction with the dichlorocarbene intermediate. This is not the case when silver tetrafluoroborate is used. 

This reaction proceeds via the deoxygenation of phosgene by atomic carbon to give the dichlorocarbene intermediate. When a gas-phase mixture of COClj and c -2-butene was used as the reactive matrix ... 

Increased para selectivity has been reported by using potassium, cesium and ammonium hydroxide as bases instead of sodium hydroxide.The addition of 6-cyclodextrin (BCD) afforded 100% para selectivity due to formation of a preferentially para ternary molecular complex between the phenolate ion, BCD and the dichlorocarbene intermediate.Although the presence of BCD does not enhance the total aldehyde production, it reduces the proportion of other isomeric aldehydes formed in favour of the para-product. Recently Zhang et. reported the synthesis of p-... 

The reaction of iminium salts such as 66 with salts of trichloroacetic acid has been shown to yield amides such as 84 on hydrolysis 126). It was suggested that the reaction proceeds by addition of dichlorocarbene to give an aziridinium intermediate (85), which was opened by trichloroacetate followed by hydrolysis to give the observed products 126). The observed products from the reaction can be accounted for by formation of CCI3,... 

The Ciamician-Dennstedt reaction can be thought of as the complement to the Reimer-Tiemann reaction (Scheme 8.3.2). The first step of both reactions is cyclopropanation of one of the carbon-carbon double bonds of a pyrrole with a dichlorocarbene, resulting in intermediate 3. The Ciamician-Dennstedt reaction results from cleavage of the internal C-C bond and elimination of chloride (path a), while the Reimer-Tiemann reaction results from cleavage of the exocyclic bond, and subsequent hydrolysis of the dichloromethyl moiety to furnish aldehyde 5 (path b). 

The idea that dichlorocarbene is an intermediate in the basic hydrolysis of chloroform is now one hundred years old. It was first suggested by Geuther in 1862 to explain the formation of carbon monoxide, in addition to formate ions, in the reaction of chloroform (and similarly, bromoform) with alkali. At the end of the last century Nef interpreted several well-known reactions involving chloroform and a base in terms of the intermediate formation of dichlorocarbene. These reactions included the ring expansion of pyrroles to pyridines and of indoles to quinolines, as well as the Hofmann carbylamine test for primary amines and the Reimer-Tiemann formylation of phenols. 

Carbon tetrachloride was also found to react with pyrryl potassium to give 3-chloropyridine, however the mechanism is obscure and would justify further investigation. In a preparatively useful reaction, pyrrole and chloroform in the vapor phase at 500-550° gave 3-chloro-pyridine (33%) and a little 2-chloropyridine (2-5%). No interconversion of the isomers occurred under these conditions, though pyrolytic rearrangement of N-alkylpyrrole to 3-substituted pyridines is considered to involve 2-alkylpyrroles as intermediates. There is some independent evidence that dichlorocarbene is formed in the vapor phase decomposition of chloroform. ... 

Reaction with chloroform under basic conditions is a common test for primary amines, both aliphatic and aromatic, since isocyanides have very strong bad odors. The reaction probably proceeds by an SnIcB mechanism with dichlorocarbene as an intermediate ... 

The reactive intermediates under some conditions may be the carbenoid a-haloalkyllithium compounds or carbene-lithium halide complexes.158 In the case of the trichloromethyllithium to dichlorocarbene conversion, the equilibrium lies heavily to the side of trichloromethyllithium at — 100°C.159 The addition reaction with alkenes seems to involve dichlorocarbene, however, since the pattern of reactivity toward different alkenes is identical to that observed for the free carbene in the gas phase.160... 

The reactions of dichlorocarbene with phosphorus ylides result in the corresponding olefins and phosphines.66-68 In the reaction of dichlorocarbene generated in situ with tributyl- and triphenylmethylenephosphoranes or triphenylethylidenephosphorane, the olefin yield increases as the nucleo-philicity of phosphorus ylide increases. According to,67 the reaction starts from the electrophilic attack of carbene at the a-C atom of phosphorus ylide. Then the intermediately formed betaine (28) (Scheme 14) decomposes to eliminate the phosphine molecule and form dichloroolefin (29). 

Diols generally react with dichlorocarbene to produce a mixture of alkenes and chlorinated cyclopropanes or chloroalkanes, depending on the reaction conditions whereas, under phase-transfer catalysed conditions, the major products are the alkenes and epoxides produced by ring closure of the initial adduct (Scheme 7.20) [14]. When an excess of chloroform is used, further reaction of the alkenes with dichlorocarbene produces the cycloadducts. In addition to the formation of the alkene and epoxide, 1,2-dihydroxycyclooctane yields cyclooctanone, via a 1,2-hydride shift within the intermediate carbenium ion. 

When ketones are reacted with dichlorocarbene in the presence of secondary amines, a-aminoacetamides are obtained via the ring opening of the intermediate oxiranes by the amine [19]. Similar products are obtained from the corresponding reactions with aniline and also with aldehydes (see Section 7.4). 

Evidence for the generation of these reactive intermediates was obtained from a study of the effect of added cydohexene on the sonication of chloroform. The presence of free radicals in the system was confirmed by the appearance of chlorocydohexane as a product and by the increased rate of decomposition of CHCI3 in the presence of cyclohexene. The increased decomposition rate is a consequence of the presence, in the cavitation bubble, of the alkene which mops up the Cl radical as it is formed and prevents the regeneration of chloroform - i. e. the kinetic steps in Scheme 3.4 are driven from left to right. Carbene intermediates are implicated by the formation of tricyclic compounds such as (1) via dichlorocarbene addition to cydohexene. 

Where we have reason to suspect the involvement of a particular species as a labile intermediate in the course of a reaction, it may be possible to confirm our suspicions by introducing into the reaction mixture, with malice aforethought, a reactive species which we should expect our postulated intermediate to react with particularly readily. It may then be possible to divert the labile intermediate from the main reaction pathway—to trap it—and to isolate a stable species into which it has been unequivocally incorporated. Thus in the hydrolysis of trichloromethane with strong bases cf. p. 46), the highly electron-deficient dichlorocarbene, CClj, which has been suggested as a labile intermediate (p. 267), was trapped by introducing into the reaction mixture the electron-rich species cis but-2-ene (11), and then isolating the resultant stable cyclopropane derivative (12), whose formation can hardly be accounted for in any other way ... 

The gaseous dichlorocarbene radical cation reacted with alkyl halides via a fast electrophilic addition to form a covalently bonded intermediate (CI2C—X—R)+ in a Fourier transform ion cyclotron resonance mass spectrometer. This intermediate fragments either homolytically or heterolytically to produce net halogen atom or halogen ion transfer product. Addition of carbonyls to the carbene ion is followed by homolytic cleavage of the C-O bond to yield a new carbene radical cation. 

A derivative of 1,3-naphthyne was postulated by Billups et al. as an intermediate of the dehydrohalogenation of the dichlorocarbene adduct of 2-bromoindene with potassium tert-butoxide however, the complex product mixture did not allow the reaction mechanism to be conclusively elucidated (Scheme 16.19). 

Although the gem-dihalocyclopropanes are fairly stable compounds, they can participate — as has been shown in the above sections — in quite a number of chemical transformations. Several reactions between dihalocarbenes and alkenes have been described in which no dihalocyclopropane formation could be observed that these intermediates might have been produced was only inferred from the type of products finally isolated. A typical process of this type is the e/ufo-addition of dihalocarbenes to norbomene and norbomadiene as discussed above. Comparable rearrangements have been observed, when dichlorocarbene additions either lead to aromatic products or when they cycloadd to rather inert aromatic systems. In the latter case a ring-enlargement takes place. A reaction related to the concerted opening of two cyclopropane rings in a bicyclopropyl system as discussed above takes place when dichlorocarbene is added to spiro[2.4]hepta-4,6-diene [227]. 

Finally, the formation of chlorocyclobutenes 25 and 27 by treatment of trimethylcyclopropene 24 with dichlorocarbene,2n and by reaction of l,l-dibromo-2,2-dichloro-3-chloromethyl-3-methylcyclopropane (26) with methyllithium 212 can be explained by disrotatory outward ring opening of an intermediate dichlorobicyclobutane with concomitant migration of an endo-ch a-rine and methylation, respectively. 

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