Acetic anhydride enolization

Preparation of enol acetates [1, 800, after citation of ref. 18] It has been shown in at least two cases that the perchloric acid catalyzed acetic anhydride enol acetylation is thermodynamically controlled.183 Thus the 3-keto-5/3-steroid, 17/3-acetoxy-50-androstane-3-one (1), on reaction with acetic anhydride-perchloric acid gives the two enol acetates (2) and (3) in the ratio 93.5 to 6.5. The calculated ratio derived from the relative stability of (2) and (3) is 96 4. If a mixture of 65% of (2)... 

As a significantly challenging system, a y-lactone synthesis via intermolecular oxycupration reaction of styrene 49 has been reported by Jiang et al. in 2010 (Scheme 23) [37]. This reaction system involves ds-oxycupration process of acetic anhydride enolate to styrene 49 and the following intramolecular insertion into the enol ester. 

Acetic anhydride can be used to synthesize methyl ketones in Friedel-Crafts reactions. For example, benzene [71-43-2] can be acetylated to furnish acetophenone [98-86-2]. Ketones can be converted to their enol acetates and aldehydes to their alkyUdene diacetates. Acetaldehyde reacts with acetic anhydride to yield ethyhdene diacetate [542-10-9] (18) ... 

The selectivity is probably impaired by bromination at C-2 and C-9. Bromination under buffered conditions of the A -enol acetate prepared from acetic anhydride with perchloric acid catalysis may give better results. See also ref. 55 for a similar bromination. 

Olefins may be obtained by elimination from the organoboron intermediates formed from enol derivatives and diborane. " As in the reaction with a,jS-unsaturated ketones (section IX), the conversion is carried out in two parts first formation of the diborane adduct and second, decomposition in refluxing acetic anhydride. 

Enol acetates are readily prepared from saturated ketones by reaction with acetic anhydride alone or diluted, in the presence of acetyl chloride ... 

Enol esterification with acetyl chloride-acetic anhydride gives the A -trien-3-acetate, but reaction with isopropenyl acetate or with hot acetic anhydride-pyridine gives A " -trien-3-acetates. " Since A"" -3-ketones react with Girard reagents, these linear dienones can be separated from A ""-3-ketones. ... 

Unsubstituted 20-ketones readily form enol acetates. Reaction with isopropenyl acetate yields the kinetic A -isomer (86, R = CH3CO) which is equilibrated to the A -enol acetate (85, R = CH3CO) on exposure to acetic anhydride-/7-toluenesulfonic acid. Treatment of the 20-ketone according to the latter conditions gives the A -enol acetate directly. 

A ( )-Enol-l 1-acetates are formed by distillation of acetic anhydride in the presence of / -toluenesulphonic acid. Another procedure employed for the synthesis of enol benzoates involves treatment with benzoic anhydride and triphenyl methyl sodium or ethynyl sodium. Suitable procedures utilizing a diluent have been developed for the enol esterification of a 20-ketone without affecting an 11-ketone. 

The dimethyl acetal (94) is readily prepared from the 22-aldehyde (93) by direct reaction with methanol in the presence of hydrogen chloride. Ena-mines (95) are formed without a catalyst even with the poorly reactive piperidine and morpholine.Enol acetates (96) are prepared by refluxing with acetic anhydride-sodium acetate or by exchange with isopropenyl acetate in pyridine.Reaction with acetic anhydride catalyzed by boron trifluoride-etherate or perchloric acid gives the aldehyde diacetate. 

A 20) oiefin Formation via Enol Acetates and Ozonolysis A stock solution of acetylating mixture is prepared by dissolving 0.2 ml of 70-72% perchloric acid in 5 ml of acetic anhydride. To a solution of 5 g of 3a,6a-diacetoxy-5jff-pregnan-20-one in 50 ml of carbon tetrachloride is added 5 ml of the above stock perchloric acid-acetic anhydride solution and the mixture is allowed to stand at room temperature for 1.25 hr. The mixture is... 

In a situation where severe steric hindrance e.g., 16,16-dimethyl-20-keto-pregnanes) prevents enol acetate formation, an alternate scheme has been devised. Condensation of ethyl oxalate at C-21 produces, after hydrolysis, the 21-glyoxylic acid this on treatment with acetic anhydride and a strong acid catalyst such as perchloric acid gives both lactone acetates. 

Coumarin formation proceeds via an intramolecular attack by enol ester 9 on the ketone to give 10. Dehydration of 10 then affords coumarin 11. It has been observed that coumarins are favored when higher order homologs of acetic anhydride and their corresponding salts such as propionic anhydride/sodium propionate and butyric anhydride/ sodium butyrate are used. 

In further modifications of these norprogestins, reaction of norethindrone with acetic anhydride in the presence of p-toluene-sulfonic acid, followed by hydrolysis of the first-formed enol acetate, affords norethindrone acetate (41). This in turn affords, on reaction with excess cyclopentanol in the presence of phosphorus pentoxide, the 3-cyclopentyl enol ether (42) the progestational component of Riglovic . Reduction of norethindrone affords the 3,17-diol. The 33-hydroxy compound is the desired product since reactions at 3 do not show nearly the stereoselectivity of those at 17 by virtue of the relative lack of stereo-directing proximate substituents, the formation of the desired isomer is engendered by use of a bulky reducing agent, lithium aluminum-tri-t-butoxide. Acetylation of the 33,173-diol iffords ethynodiol diacetate, one of the most potent oral proves tins (44). ... 

Due to the nonaromatic character of the oxepin system the oxepinones do not usually form stable enol structures. By O-acylation or O-alkylation, however, the enol forms can be stabilized as enol esters and ethers, respectively. A large number of substituted 1-benzoxepins have been synthesized by this route. Acetylation of l-benzoxepin-3(2//)-ones 1 and l-benzoxepin-5(2/T)-ones 3 was readily achieved with acetic anhydride in the presence of an appropriate base such as pyridine, triethylamine or sodium acetate.t5,t6 t72 176... 

Due to their thermal instability, this method cannot be applied to the preparation of benzo-thiepins. Although the ft-oxo sulfoxide moiety in precursors such as 5-methoxy-4-phenyl-l-benzothiepin-3(2/7)-one 1-oxide makes them candidates for a Pummerer reaction, treatment with acetic anhydride and triethylamine at - 30 C results in preferential enol acetylation to afford the corresponding 1-benzothiepin 1-oxide.14... 

The monoacetate 9a (R1 = Ac) and the diacetate 10a (R1 = R2 = Ac) are obtained by treatment of 8 with acetic anhydride in anhydrous pyridine at room temperature 4 the oxo group in position 5 of 8 is more reactive towards acetylation. Similarly, the S,S-dioxidc of 8 can be converted to the bisacetylated S,5-dioxide of 10a in 78 % yield.74 Methylation of 8 with diazomethane gives 9c (65 % yield), along with 14 % of the 3-methoxy compound 11. Other alkylation agents, such as dimethyl sulfate in the presence of potassium carbonate, selectively give 9c, albeit in lower (30 %) yield.90 The dimethyl enol ether 10c (R1 = R2 = Me) is obtained by a subsequent methylation of 9c (R1 = Me) with dimethyl sulfate and potassium teri-butoxide.90... 

Hydroxy-substituted iron-acyl complexes 1, which are derived from aldol reactions of iron-acyl enolates with carbonyl compounds, are readily converted to the corresponding /i-methoxy or /1-acetoxy complexes 2 on deprotonation and reaction of the resulting alkoxide with iodomethane or acetic anhydride (Tabic 1). Further exposure of these materials to base promotes elimination of methoxide or acetate to provide the a,/ -unsaturated complexes (E)-3 and (Z)-3 (Table 2). 

Acetylation of acetals or ketals can be accomplished with acetic anhydride and BF3-etherate. ° The mechanism with acetals or ketals also Involves attack at an alkenyl carbon, since enol ethers are intermediates. Ketones can be formylated in the a position by treatment with CO and a strong base. ... 

Enol lactones can also be obtained from keto acids by enolization-dehydration. Adlumidiceine (103) as well as N-methylhydrasteine (104) when heated in toluene with acetic anhydride or p-toluenosulfonic acid were transformed to enol lactones 97 (97) and 98 (5,102), respectively. Narceine (106) under the influence of PC13 yielded 101 (87,100). 

In order to construct the thiepin conjugation, the seven-membered cyclic ketones containing sulfur could be converted to either their enol ethers or enol acetates. The resulting thiepins should have a number of substituents. The first stable 3,5-diacetoxy-4-phenylbenzo[6]thiepin (15) has been obtained by Hofmann et al. from the diketone (14) by acetylation with acetic anhydride in pyridine in good yield 13). By this methodo-... 

Nitration of ketones or enol ethers provides a useful method for the preparation of a-nitro ketones. Direct nitration of ketones with HN03 suffers from the formation of a variety of oxidative by-products. Alternatively, the conversion of ketones into their enolates, enol acetates, or enol ethers, followed by nitration with conventional nitrating agents such as acyl nitrates, gives a-nitro ketones (see Ref. 79, a 1980 review). The nitration of enol acetates of alkylated cyclohexanones with concentrated nitric acid in acetic anhydride at 15-22 °C leads to mixtures of cis- and rrans-substituted 2-nitrocyclohexanones in 75-92% yield. 4-Monoalkylated acetoxy-cyclohexanes give mainly m-compounds, and 3-monoalkylated ones yield fra/w-compounds (Eq. 2.40).80... 

A convenient and general method has been developed for the synthesis of alkylpyrroles starting from ketones and nitroalkenes via reduction of the intermediate acetic nitronic anhydride as shown in Eq. 10.1. Ketone enolates react with a variety of nitroalkenes to yield the Michael adducts, lithium nitronates, which are trapped with acetic anhydride to give the corresponding acetic nitronic anhydrides. The acetic nitronic anhydrides are easily converted into alkylpyrroles by reduction with Zn(Cu).3... 

The Michael addition of lithium enolates to nitroalkenes followed by reaction with acetic anhydride gives acetic nitronic anhydrides, which are good precursors for 1,4-diketones, pyrroles, and pyrrolidines (Eq. 10.73).113... 

The kinetics of the acid-catalyzed esterification reaction of 2,4,6-trimethylbenzoic acid in i-PrOH under microwave irradiation have been investigated [84], A simple and practical technique for MW-assisted synthesis of esters has been reported wherein the reactions are conducted either on solid mineral supports or by using a phase transfer catalyst (PTC) in the absence of organic solvents [85], The esterification of enols with acetic anhydride and iodine has also been recorded [86],... 

Another example of the formation of an octalin is the conversion of the cyclohexenone 127 into the enol acetate 128 by the action of acetic anhydride and perchloric acid in the presence of acetic acid (equation 65)75. The acid-induced ring-closure of the cyclopentane derivative 129 gives a 85% yield of a mixture of the octahydroazulenes 130 and 131... 

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