Dichlorocarbene reaction with ketones

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). 

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. 

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],... 

The reaction of dichlorocarbene with ketones and diamines results in near quantitative formation of a mixture piperazinones 584 and 585 (80JOC754). As shown in Section III,C,2, piperazine 78 [R = H, R + R = (CH2)s], the minor product of the Rh2(OAc)4-catalyzed decomposition of diazo ester 73, is the result of the dimerization of the intermediate ylide 76 (84JOC113). Tetrahydropyrazines were synthesized through ring expansion of imidazolidines. Thermolysis or photolysis of diazo compounds... 

The term phase transfer catalysis was coined by Starks to describe the mechanism of catalysis of reactions between water-soluble inorganic salts and water-insoluble organic substrates by lipophilic quaternary ammonium and phosphonium ions Ql). His investigations of nucleophilic displacement reactions, such as that of aqueous sodium cyanide with 1-chlorooctane, and the investigations of Makosza on reactions of aqueous sodium hydroxide with chloroform to generate dichlorocarbene, and with active ketones and nitriles to generate carbanions, pioneered the field in the mid-1960 s. It was nearly fifteen years before many such processes were adopted in industry. Starks now estimates there are about sixty phase transfer catalytic processes in use worldwide, mostly in pharmaceutical and fine chemical manufacturing (32V... 

The reaction of enamines derived from cyclohexanone with dichlorocarbene to give the 1 1 adducts is now well established (137-139). The morpholine enamine (113) reacted with dichlorocarbene at —10 to —20° in tetrahydrofuran to give the stable crystalline adduct (201). Thermal decomposition followed by an aqueous work-up gave an a,)3-unsaturated ketone identified as 2-chloromethylene-cyclohexan-l-one (202) (139). 

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). 

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... 

Antidepressant activity is retained when the double bond in the cycloheptene ring is replaced by a fused cyclopropane. The starting material for this compound is obtained by the reaction of unsaturated ketone (24-6) with dichlorocarbene... 

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. ... 

Dichloromethyl ketones. Dichlorocarbene generated by the Makosza technique reacts with acetals of type 1 to form ketals of dichloromethyl ketones (2). The same reaction is observed with dibromocarbene. The R group of 1 can be hydrogen, alkyl, or aryl. ... 

An interesting ring expansion of cyclic ketones via reaction of the corresponding eneamines with dichlorocarbene has been observed. In this way, ketone 4 was obtained in good yield. Also, triethyloxoniiim salts effect ring expansion in diazoketones such as to afford the corresponding diketones. ... 

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). 

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