Enolate chlorination

The enolic chlorine at the 3 position in (32-6) can be removed under reductive conditions such as zinc and acid to give the cephem (34-1) that now... 

Write the structures of the enol forms of 2 butanone that react with chlorine to give 1 chloro 2 butanone and 3 chloro 2 butanone... 

Represent the reaction of chlorine with each of the enol forms... 

Rapid halogenation of the a carbon atom takes place when an enolate ion is generated m the presence of chlorine bromine or iodine... 

As m the acid catalyzed halogenation of aldehydes and ketones the reaction rate is mde pendent of the concentration of the halogen chlorination brommation and lodmation all occur at the same rate Formation of the enolate is rate determining and once formed the enolate ion reacts rapidly with the halogen... 

The compounds 2- (16) and 4-pyridone (38) undergo chlorination with phosphoms oxychloride however, 3-pyridinol (39) is not chlotinated similarly. The product from (38) is 4-chloropyridine [626-61-9]. The 2- (16) and 4-oxo (38) isomers behave like the keto form of the keto—enol tautomers, whereas the 3-oxo (39) isomer is largely phenolic-like, and fails to be chlotinated (38). 

Enols of simple ketones can be generated in high concentration as metastable species by special techniques. Vinyl alcohol, the enol of acetaldehyde, can be generated by very careful hydrolysis of any of several ortho ester derivatives in which the group RC02 is acetate acid or a chlorinated acetate acid. ... 

Since many steroidal double bonds will react with peracids, these must be protected before the enol acetylation step. Chlorination is generally satisfactory for this purpose. ... 

Reaction of 1-ethoxycyclohexene (34) with dichlorocarbene gives 1-ethoxy-7,7-dichloronorcarane (35) in 87 % yield. Rearrangement of dichlorocyclo-propane (35) in hot quinoline results in loss of both chlorine atoms to give l-ethoxycyclohepta-l,3,5-triene (37) in 37% yield. Hydrolysis of enol ether (37) with a very small quantity of hydrochloric acid in methanol produces cyclohepta-3,5-dienone (38) in 91 % yield. ... 

In this paper Speziale and Smith 109) described experiments which led them to modify the mechanism proposed earlier 108) for the reaction of trivalent phosphorus compounds with haloamides. The first step is considered to be attack of the trivalent phosphorus compound on a chlorine atom of the halo amide (132) to produce a resonance-stabilized enolate ion (133). This is reasonable since under conditions where the trichloroamide... 

The formulated mechanism is supported by the finding that no halogen from the phosphorus trihalide is transferred to the a-carbon of the carboxylic acid. For instance, the reaction of a carboxylic acid with phosphorus tribromide and chlorine yields exclusively an a-chlorinated carboxylic acid. In addition, carboxylic acid derivatives that enolize easily—e.g. acyl halides and anhydrides—do react without a catalyst present. 

Halogenation of steroid 3-ketones can lead to complicated mixtures by virtue of the fact that the kinetic enol leads to 3 halo products, whereas the thermodynamic product is that halogenated at the 4 position. Carefully controlled reaction of the 5a-androstanolone with chlorine thus leads to the 2a-chloro derivative (29). Reaction of that intermediate with O(p-nitrophenyl)-hydroxylamine affords the androgenic agent ni stremine acetate (30). ... 

The chlorophylls produced by bacteria, algae and plants are a natural source of chlorins. The isolation of chlorophylls from natural material is known to be difficult because of their extreme sensitivity to various reactions, such as enolization, epimerization, allomerization, de-methoxycarbonylation, solvolysis, demctalation, dephytylation, photooxidation, etc. Often the... 

When the nucleophile is a stabilized carbanion such as the enolate of acetylacetone, 1-benzoylacetophenone, diethylmalonate, or ethyl acetatoacetone, the reaction proceeds similarly. The monosubstituted complex is isolated as long as it contains an acidic hydrogen in the benzylic position. In addition, for the case of diketones CH2(COR)2 (R = Me, Ph, OEt), a deacetylation is observed in an acidic medium [92,93]. These features are the same as described above in the case of the substitution of Cl by stabilized carbanions in monochloroaromatics (the second chlorine being an inert arene substituent [99] Scheme XVII, Eq. (31) and Tables 10 and 11. 

The mean value of k for a large number of liquids is 2 12 liquids containing hydroxyl groups, or those which have an enolic modification, liquid chlorine, fused salts, and metals, have much smaller values of k, and this is attributed to polymerisation, since if the actual molecular weight is larger than that assumed in calculating V , the latter value will also be smaller. Ramsay and Aston (1894) assumed that it will be proportionally smaller, but the values of the polymerisation coefficients thereby deduced obviously depend on the formula assumed for the polymerised molecule, and are therefore arbitrary. 

The first step, as we have already seen (12-3), actually consists of two steps. The second step is very similar to the first step in electrophilic addition to double bonds (p. 970). There is a great deal of evidence for this mechanism (1) the rate is first order in substrate (2) bromine does not appear in the rate expression at all, ° a fact consistent with a rate-determining first step (3) the reaction rate is the same for bromination, chlorination, and iodination under the same conditions (4) the reaction shows an isotope effect and (5) the rate of the step 2-step 3 sequence has been independently measured (by starting with the enol) and found to be very fast. With basic catalysts the mechanism may be the same as that given above (since bases also catalyze formation of the enol), or the reaction may go directly through the enolate ion without formation of the enol ... 

So do anhydrides and many compounds that enolize easily (e.g., malonic ester and aliphatic nitro compounds). The mechanism is usually regarded as proceeding through the enol as in 12-4. If chlorosulfuric acid (CISO2OH) is used as a catalyst, carboxylic acids can be ot-iodinated, as well as chlorinated or brominated. N-Bromosuccinimide in a mixture of sulfuric acid-trifluoroacetic acid can mono-brominate simple carboxylic acids. ... 

A number of other methods exist for the a halogenation of carboxylic acids or their derivatives. Acyl halides can be a brominated or chlorinated by use of NBS or NCS and HBr or HCl. The latter is an ionic, not a free-radical halogenation (see 14-2). Direct iodination of carboxylic acids has been achieved with I2—Cu acetate in HOAc. " ° Acyl chlorides can be a iodinated with I2 and a trace of HI. Carboxylic esters can be a halogenated by conversion to their enolate ions with lithium A-isopropylcyclohexylamide in THF and treatment of this solution at -78°C with... 

In a related reaction, enolate 71 is undergoing an electrophilic chlorination with 2,2,6,6-tetrachloro-cyclohexanone (74, Fig. 39), eventually leading to a-chlorinated enol esters 75 [91]. However, a different mechanism cannot be completely ruled out, where the catalyst is not acylated by the ketene, but chlorinated by the tetrachloro-ketone to form [64c-Cl] as the reactive species. 

Enolizahon of cyanoketone rac-5 under the previously optimized conditions, followed by reaction with p-toluenesulfonic anhydride afforded a 90 10 ratio of the two expected enol tosylates in 90% yield. An immediate advantage of the tosylates compared to the triflate was seen on isolation, when the desired compound 32 was found to be a crystalline solid. In this way an 85% isolated yield of 32 as a single isomer could be achieved without the need for chromatography (Scheme 9.24). Use of p-toluenesulfonyl chloride in place of the anhydride led to a-chlorination... 

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