Dichlorocarbene reaction with aldehydes

When the reaction with substituted benzaldehydes is conducted in the presence of ammonia, the a-amino carboxylic acids are formed [11], The corresponding reaction involving bromoform is less effective and, for optimum yields, the addition of lithium chloride, which enhances the activity of the carbonyl group, is required. In its absence, the overall yields are halved. The reaction of dichlorocarbene with ketones or aryl aldehydes in the presence of secondary amines produces a-aminoacetamides [12, 13] (see Section 7.6). 

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). 

Aldoximes are normally dehydrated by reaction with dichlorocarbene, produced under soliddiquid two-phase conditions, to yield nitriles in high yield [41, 42], whereas a-hydroxy ketoximes are cleaved with the simultaneous formation of a nitrile and either an aldehyde or ketone (Scheme 7.33). Yields are generally >70% and, in the case of cyclic hydroxy ketoximes, the products are acyclic oxo nitriles [43],... 

Phenols are smoothly converted into phenolic aldehydes by reaction with chloroform in the presence of base (the Reimer-Tiemann reaction). This overall formylation reaction is of interest in that it involves the generation from chloroform and alkali of the reactive intermediate, dichlorocarbene (2). This effects electrophilic substitution in the reactive phenolate ions giving the benzylidene dichloride (3) which is hydrolysed by the alkaline medium to the corresponding hydroxyaldehyde. The phenolic aldehyde is isolated from the reaction medium after acidification. 

The 3,4-dioxoperhydro derivative of (3) was obtained by cross carbonylation of 2-hydroxymethyl-pyridine <87CC125>. Reaction of Schiff bases, prepared from 2-aminopyridine and its 5,6-benzologue with aldehydes and dichlorocarbene, afforded 2-aryl-3-chloro-4-oxo-4/f derivatives of (12) and its 6,7-benzologue <9lKGS8io>. 

The reactions of dichlorocarbene with morpholine and piperidine enamines derived from cyclopentanone and cyclohexanone have been reported to lead to ring expanded and a-chloromethylene ketone products (355,356). Similarly a-chloro-a, -unsaturated aldehydes were obtained from aldehyde derived enamines (357). Synthesis of aminocyclopropanes (353,359) could be realized by the addition of diphenyldiazomethane (360) and the methylene iodide-zinc reagent to enamines (367). 

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). 

Dioxanes and dioxolanes, derived from alkyl and aryl aldehydes, react with dichlorocarbene specifically at the C-2 position, with no evidence of reaction at C-4 or C-5 (Scheme 7.2). The yields are variable, but provide a convenient route to dichloromethyl ketones [13, 14], The rate of insertion into the C-H bond correlates with the electronic character of the 2-aryl substituent and is also influenced by... 

Methylpyrrolo(2,3-6]pyridine reacts with dichlorocarbene (Reimer-Tiemann reaction) to give the aldehyde (51) with no trace of a ring-expanded product (68AHC(9)27). On the other hand, the 2-phenyl compound gives the chloropyridine (52) and no aldehyde... 

Dehydroaporphines undergo both N- and C-7-protonation in trifluoroacetic acid, but it is the C-7-protonated immonium salt which is formed almost exclusively under equilibration conditions.41 Some C-6a- and C-7-deuteriated aporphines can, therefore, be prepared. The reaction of dehydronuciferine with dichlorocarbene yielded dehydronuciferine-7-carboxaldehyde. Reduction of this aldehyde with sodium cyanoborohydride afforded 7-methyldehydro-nuciferine.42... 

Using bromodichloromethyl(phenyl)mercury, vinyl acetate afforded 2-acetoxy-l,l-dichlo-rocyclopropane (1, 85%), dichlorocyclopropanation of other aldehyde enol esters would also be expected. The cyclopropane 1 ( 10%) together with 2-acetoxy-l,l,l-trichloropropane (2,10%) were formed when the dichlorocarbene was generated from sodium trichloroacetate, the chain product 2 results from the reaction of the trichloromethyl anion (for the mechanism, see ref 197). These reactions are described in Houben-Weyl, Vol. 4/3, pp 177-178. Under phase-transfer catalytic conditions (CHClj/base/PTC), with a typical catalyst such as benzyl-triethylammonium chloride, vinyl acetate gave 2 (65%) only (Houben-Weyl, Vol.E19b, ppl550-1551). 

It is interesting to compare early experimental work with the facilities available in a modem laboratory. Von Auwers was the first to separate the chloro ketones from the normal phenolic aldehydes of the Reimer-Tiemann reaction. Identirication and strocture proof by chemical means followed. It is a tribute to von Auwers skill and insight that his identification procedures have withstood the onslaught of modem spectroscopic means. Although the chloro ketones (equations 8-10) have been called the abnormal products of the reaction, in cases where the ortho and para positions are occupied (see equation 10) only ketonic material is obtained.In fact, the presence of the dichloro ketones provides one of the better arguments for the intermediacy of dichlorocarbene in the reaction mechanism. ... 

In Equation (6), the resulting dichlorocarbene and the phenolate ion tmdergoes a reversible reaction to form an intermediate, which subsequently loses a proton and then gains a proton to 3deld the benzylidene dichloride. The benzylidene dichloride on being subjected to a treatment with an alkali followed by the hydronium ion yields the corresponding ort/io-hydroxy aldehyde (or salicylaldehyde). 

Sol 9. (d) Aldehydes and ketones having a-protons react with secondary amines to form enamines. The enamine formed in the first step undergoes cyclopropanation reaction at the double bond with dichlorocarbene that is generated by a-elimination of HCl from chloroform. This product undergoes ring expansion to furnish 2-chlorocyclohex-2-en-l-one (I). 

Reaction of dichlorocarbene with dehydronuciferine yields dehydro-nuciferine-7-carboxaldehyde. Reduction of this aldehyde with sodium cyano-borohydride at pH 3 affords in good yield 7-methyldehydronuciferine. Alternatively, sodium borohydride reduction of the aldehyde succeeded by treatment with hydrogen cyanide affords 7-cyanomethyldehydronuciferine. (See Scheme 10.7.)... 

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