Enamine, a-chloro

Recently a-chloro-)3-chlorocarbonyl enamines have been obtained from ynamines and phosgene (121a). 

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). 

Most a-chloro enamines can be readily converted into the corresponding a-fluoro enamines by reaction with potassium or cesium fluoride or to the iodo enamines by reaction with potassium iodide. All a-halo enamines are highly hygroscopic and must be stored in sealed tubes. 

Few publications are devoted to the synthesis of imidazole derivatives the reaction between A-chloro-A -benzenesulfonylamidines with enamines shown in Scheme 9 serves as an example (87T4785). 

Fig. 6.12. Acid-free preparation of carboxylic chloride from carboxylic acids and a chloro-enamine.

Figure 6.12 shows that carboxylic acids can also be converted into carboxylic chlorides without releasing HC1. This is possible when carboxylic acids are treated with the chloro-enamine A. First the carboxylic acid adds to the C=C double bond of this reagent electrophilically (mechanism Figure 3.40, see also Figure 3.42). Then, the addition product B dissociates completely to give the ion pair C it constitutes the isopropyl analog of the Vilsmeier-Haack intermediate B of the DMF-catalyzed carboxylic chloride synthesis of Figure 6.11. The new Vilsmeier-Haack intermediate reacts exactly like the old one (cf. previous discussion) The chloride ion undertakes an SN reaction at the carboxyl carbon. This produces the desired acid chloride and isobutyric N,N-dimethylamide.

Amide should be first transformed to its hydrochloride in order to cut down the formation of a-chloro-jf(-chlorocarbonyl enamines 72,73). The method is very general but the choice of experimental conditions and of the base is critical and yields may vary strongly depending on the case (39). There is also one side-reaction which can hardly be avoided the ynamine already formed reacts with the yet unreacted amide chloride, the a-chloroenamine 70) or even with the tert-amine hydrochloride to form the very stable cyclobutene cyanines and/or allenamidinium salts. These by-products have an interest of their own and will be discussed later. Formation of these salts may strikingly lower the yield of ynamines, but because of their salt character they are not harmfull during the work-up72). 

Cyclopropanes have also been obtained by reaction of enamines with a-chloro electrophilic alkenes. After Michael addition the chlorine undergoes nucleophilic displacement by the regenerated enamine or enolate anion260,261 (Scheme 112). Bicy-clo[ 1.1.0] butanes may be obtained by cycloaddition of trimethyl ethylenetricarboxylate followed by a base catalysed displacement of the amine moiety262 (Scheme 113). 

Preparation. This a-chloro enamine (1) is prepared in about 80% yield by the reaction of phosgene with N,N-dimcthylisobutyramide followed by elimination of hydrogen chloride with triethylamine. ... 

Appropriately functionalized alkenes (enamines, a-haloalkenes, silylenoi ethers, acylvinyl phosphonium salts) are frequently employed as the CC fragment in reaction with amidines, guanidines and ureas. An -chloro-A -alkylamidine will react with the enamine derived from an aldehyde to give in the first instance a 2-imidazoline (4). Such compounds deaminate readily to produce the fully aromatic imidazoles (5), especially when heated with pyridinium or triethylammonium chlorides or 50% sulfuric acid (Scheme 4.3.3). 

The ring contraction of 2-halocyclohexanone enamines has been discussed in Section 4.3.12. The preparation of aminocyclopropane derivatives from the enamines of substituted a-chloro-cycloheptanones showed some restrictions. The substituent influences both the energy difference between the aminoallyl cation and cyclopropiminium ion and a subsquent homoenamine ring opening. 

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