4-Hydroxy acetophenone reaction with methyl

Comparisons of structurally related hydroxy- and methoxy-substituted cations show that hydroxy is more stabilizing by between 4 and 5 log units. This difference was recognized 20 years ago by Toullec who compared pifas for protonation of the enol of acetophenone and its methyl ether145 (-4.6 and 1.3, respectively) based on a cycle similar to that of Scheme 15, but with the enol replacing the hydrate, and a further cycle relating the enol ether to a corresponding dimethyl acetal and methoxycarbocation.146 Toullec concluded, understandably but incorrectly, that there was an error in the pA a of the ketone (over which there had been controversy at the time).147,148 In a related study, Amyes and Jencks noted a difference of 105-fold in reactivity in the nucleophilic reaction with water of protonated and O-methylated acetone and concluded that the protonated acetone lacked a full covalent bond to... 

This type of reaction was first used by Dilthey and Fischer69 in connection with the mechanism of the type in Section II, D, 2. By analogy with the well-known formation of benzopyrylium salts from methyl(ene) ketones and o-hydroxybenzaldehyde or o-hydroxy-acetophenone,340 benzoylacetone (84, R = Me, R = H, R" = Ph) and acetophenone (85, RIV = Ph, R" = H) afforded in the presence of acetic anhydride and sulfuric acid, 2-methyl-4,6-diphenylpyrylium sulfoacetate. The interesting feature of this reaction is that a unique product is obtained (i.e., only the carbonyl group of the diketone adjacent to the phenyl enters the condensation, although two such groups are available) R and R" could be reversed, but they are not.69-69 Similarly, dibenzoylmethane (84, R = R" = Ph, R =H) afforded 2,4,6-triphenylpyrylium with acetophenone in 80% yield.69... 

Preparation from 3-chloromethyl-2-hydroxy-5-methyl-acetophenone (b.p. 110-116°) [2494] by reaction with methanol in the presence of concentrated hydrochloric acid and iron powder at reflux for 3.5. 5 h (82%) [3262], (49%) [2494]. 

Obtained by reaction of methyl iodide with 2-hydroxy-4,6-dimethoxy-5-(2-hydroxyethyl) acetophenone (m.p. 133-134°) in chloroform in the presence of silver oxide at r.t. overnight (25%) [3407]. 

Preparation by reaction of methyl iodide on the Na salt of 4-fluoro-2-hydroxy-acetophenone obtained by treatment with sodium hydride in DMF at 0° for 1 h (92%) [3903],... 

In acetophenone therefore, sulfonation occurs both in the aromatic ring and in the side chain however, in the case of 4-substituted acetophenones both reactions do not necessarily occur, For instance, the 4-methyl-, 4-hydroxy- and 4-methoxy- acetophenones all reacted with excess chlorosulfonic acid to give the corresponding 3-sulfonyl chlorides. Chapman claimed that acetophenone reacted with chlorosulfonic acid at 120 °C to give 3-chlorobenzothiophene-l,l-dioxide-2-sulfonyl chloride. 

Reaction of 9-bromomethyl-4-oxo-4//-pyrido[ 1,2-a]pyrimidine-3-carboxylates 505 and their homologs with 2,4-dihydroxy-3-propyl-and -3-allyl-acetophenone 506 in boiling methyl ethyl ketone in the presence of potassium carbonate afforded 9-(4-acetyl-3-hydroxy-2-substituted phenoxymethyl) derivatives (507) [87EUP242230 88JAP(K)88/246375]. 

Methyl 4-0-(4-methoxybenzyl)2,3-di-0-methyl-oc-D-glucopyranoside has been prepared [371] by Liptak s procedure (see Sect. 2.6). This lithium aluminium hydride — aluminium trichloride method was also used in the synthesis of 4-hydroxy-3-methoxy-benzyl [372], 4-hydroxy-3,5-dimethoxybenzyl [372], and 1-phenylethyl [373] ethers from the 4,6-acetals derived from vanillin, syringealdehyde, and acetophenone. Various vinylbenzyl ethers were prepared by the reaction of carbohydrates with vinylbenzyl chloride, and copolymerized with styrene [374]. 

Preparation by reaction of bromine with 4-hydroxy-3-methyl-acetophenone in aqueous acetic acid, first at 5°, then at r.t. (89%) [1825]. 

Obtained (by-product) by reaction of boron tribromide (4 equiv.) with 2,4-bis(benzyloxy)-5-(3-hydroxy-3-methyl-butynyl)acetophenone in methylene chloride for 5 min at 0° (14%) [3432]. 

Obtained (by-product) by reaction of m-chloro-perbenzoic acid with 5-allyl-2-hydroxy-4-[6-(methyl-thio)hexyloxy] acetophenone in methylene chloride, first at 0°, then at r.t. (9%) [2678,2679]. 

Also obtained by reaction of dimethyl sulfate with 2-hydroxy-4,6-dimethoxy-3-methyl-acetophenone,... 

Obtained by reaction of diazomethane with 2,4,6-trihydroxy-3-(3-methyl-2-butenyl)- acetophenone in ethyl ether [4335], (90%) [4359], (20%) [4322]. Also obtained by reaction of prenyl bromide with 2-hydroxy-4,6-dimethoxyac-etophenone in the presence of potassium carbonate in refluxing acetone for 8 h [4360,4361]. 

Obtained by reaction of bromine with 2-hydroxy-4-methyl-acetophenone in chloroform in an ice bath for 2 h [4383]. 

In 1991, Wright et al. reported a procedure for the preparation of substituted 1-benzyl-1//-1,2,3-triazoles 21 and 23 from benzyl azides 20 under very mild conditions (Scheme 4.7) [9]. Benzyl azides 20 reacted with active methylene compounds in DMSO induced by potassium carbonate at 35-40 C to give 1-benzyl-1//-1,2,3-triazoles 21 and 23 usually in good yield. Acetonitrile derivatives 10 gave 5-amino-l-benzyl-l//-l,2,3-triazoles 21, whereas diethyl malonate gave 5-hydroxy-l-benzyl-l//-l,2,3-triazoles. l//-l,2,3-Triazole-4-carboxylate esters and l//-l,2,3-triazole-4-ketones were obtained from ethyl acetoacetate and P-diketones, respectively. Benzyl methyl ketone reacted to give a 5-methyl-4-phenyl-l//-l,2,3-triazole, but acetone and acetophenone failed to react. Other active methylene compounds that did not react under these reaction conditions included ethyl cyanoacetate, ethyl fluoroacetate, and ethyl nitroacetate. 

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