Acetamide enol

Fig. 6. +NR+ mass spectra of (top) acetamide enol and (bottom) acetamide. Neutralization with CH3SSCH3 at 70% transmittance, reionization with 02 at 70% transmittance...

The deprotonation of BSA using lithium diisopropylamide was used to generate the protected acetamide enolate ion for use in the synthesis of the dienone shown in eq 22. It has been shown subsequently that the same product can be prepared by the reaction of the anion, generated from n-butyllithium and BSA, with 2,6-dibromo-l,4-benzoqurnone. The anion has also been used in reactions with a number of carbonyl compounds, including benzophenone. ... 

Molecules that contain two or three bulky aryl groups. An example is 2,2-dimesitylethenol (112). In this case, the keto content at equilibrium is only In cases such as this steric hindrance (p. 189) destabilizes the keto form. In 112 the two aryl groups are 120° apart, but in 113 they must move closer together (w 109.5°). Such compounds are often called Fuson-type enols ° There is one example of an amide with a bulky aryl group, A-methyl l w(2,4,6-triisopropylphenyl)acetamide, that has a measurable enol content, in sharp contrast to most amides. 

The enolized form of 2-acetyl-2-cyclohexen-l-one has been synthesized in low yield by dehydrochlorination of 2-acetyl-2-chlorocyclohexanone in collidine at 180° and by elimination of acetamide from 3-acetamido-2-acetylcyclohexanone at 120-140°. The preparation of other a,/3-unsaturated /3-dicarbonyl compounds has been attempted with varying degrees of success. The... 

Acetamido-2-acetylcyclohexanone (enol form) Acetamide, N-(2-acetyl-3-hydroxy-2-cyclohexen-l-yl)- (9) (35241-91-9)... 

Scheme 9.19 Amidation of the enol triflate with acetamide.

In general, LiBr and NEt3 are employed in 1.5 and 1.2 equiv, respectively. Although the reaction becomes rather slower, catalytic amounts of LiBr/NEt3 (0.1 equiv each) are also sufficient. In reactions with the highly reactive dipolarophile N-methylmaleimide, the catalytic reaction results in a better yield. A similar lithiation is possible with a-substituted (alkylideneamino)acetates and (alkylideneamino)-acetamides to generate lithium enolates (86). Cycloadditions with a variety of a,(3-unsaturated carbonyl compounds leads to endo cycloadducts. However, the reaction with acrylonitrile is again nonstereoselective. 

Smietana, M., and Mioskowski, C., Preparation of silyl enol ethers using (bistrimethylsilyl)acetamide in ionic liquids, Org. Lett, 7,1037-1039,2001. 

The first starting material for building benzodiazepines was prepared inadvertently in a synthesis aimed at the benzodiazoxepine (6-1). The oxime acetamide (6-2) from 2-aminobenzophenone was thus treated with hydrogen chloride in the expectation that the new heterocycle would form by the elimination of water between the oxime and the enol form of the amide. The product mrned out in fact to be the quinazoline A-oxide (6-3), the product from the addition of the nucleophilic oxime nitrogen to the amide carbonyl group. 

Most of the information on simple a-arylation reactions on the enolates of amides comes from a single study by Rossi and Alonso.128 They showed that with acetamide itself no arylation reactions took place, presumably on account of ionization of the N—H rather than the C—H bond and the observation that the... 

Chlorophenyl)glutarate monoethyl ester 87 was reduced to hydroxy acid and subsequently cyclized to afford lactone 88. This was further submitted to reduction with diisobutylaluminium hydride to provide lactol followed by Homer-Emmons reaction, which resulted in the formation of hydroxy ester product 89 in good yield. The alcohol was protected as silyl ether and the double bond in 89 was reduced with magnesium powder in methanol to provide methyl ester 90. The hydrolysis to the acid and condensation of the acid chloride with Evans s chiral auxiliary provided product 91, which was further converted to titanium enolate on reaction with TiCI. This was submitted to enolate-imine condensation in the presence of amine to afford 92. The silylation of the 92 with N, O-bis(trimethylsilyl) acetamide followed by treatment with tetrabutylammonium fluoride resulted in cyclization to form the azetidin-2-one ring and subsequently hydrolysis provided 93. This product was converted to bromide analog, which on treatment with LDA underwent intramolecular cyclization to afford the cholesterol absorption inhibitor spiro-(3-lactam (+)-SCH 54016 94. 

A. C. Amyes, T. L. Formation and stability of enolates of acetamide and acetate anion an Eigen plot for proton transfer at y-carbonyl carbon./. Am. Chem. Soc. 2002, 124, 2957— 2968. 

Silyl enolates generated from a-allyloxy ketones undergo the [2,3]-Wittig rearrangement in the presence of a catalytic Lewis base such as lithium 2-pyrrolidone, lithium acetamide, or lithium hexamethyldisilazide (Scheme ll).15... 

N, A-Dialkylacetamide enolate ions (143) were proved to react with aryl halides in liquid ammonia giving A,A-dimethyl-a-arylacetamides together with some A,A-dimethyl-a, a-diarylacetamides189. In order to synthesize some herbicides of the amide family, a series of A,A-dimethyl a-aryl and a,a-diaryl acetamides were prepared by the reaction of aryl halides (Phi, /7-iodoanisole, / -iodotoluene, 1-iodonaphthalene, 9-bromophenan-threne, 9-bromoanthracene and/ -iodobenzoic acid) with 143 (equation 95)190. The product distribution was shown to be dependent on the 143/aryl halide ratio. With a ratio of 5, approximately 50% of 144 and 20% of 145 were obtained. 

SCHEME 56. Left lithium enolate (A) and azaenolate (B) of acetamide (energies at the MP2/ZPE level). Right intramolecular chelation scheme in lithium diazaenolate of H2NCO-CH(CH3)NH-CHO216... 

THF205. More recently, the acetamide AcNH2 bare enolate has been re-inspected by DFT methods218. In particular, a 5-7 kcal mol 1 rotation barrier of the pyramidalized NH2 group has been computed (in agreement with experiment), for the monomer as well as for the mixed aggregate with LiOH. 

On the other hand, the condensation of Gamer s aldehyde574 with the non-chiral lithium enolate of diethylacetamide in non-chelating conditions occurs preferentially on the 57-face with a moderate 37% d.e. The same reaction using the enolate of (R.R)- or (5,5)-pseudoephedrine acetamides resulted in identical anti aldol adducts, but with an amplification of the face recognition of the aldehyde for the matched (R, W )-pscudoephedrine (d.e. = 96%). On the other hand, the mismatched (5,5)-pseudoephedrine gave only 12% d.e. (Scheme 120)575. 

SCHEME 120. Diastereoselective addition of pseudoephedrine acetamide lithium enolates on (1 )-Gamer s aldehyde575... 

The enol of acetamide (6) is also quite stable as an isolated species, as documented by the dominant survivor ion in the +NR+ mass spectrum (Fig. 6). Compared to 6, the thermodynamically more stable neutral acetamide (7) shows less... 

Hydroxy acetamides. The (R)-sulfinyljcetamidcs (2) obtained by reaction of the enolate of N,N-dialkylacetamides with 1 undergo an aldol-type reaction with aldehydes in the presence of base. The adducts (3) arc desulfurized to optically active P-hydroxy... 

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