Hydrolysis of anisoles

The rates of hydrolysis of a series of substituted anisoles have also been reported. The reactions are shown in Fig. 9.21, and the rate constants, along with the a values, are summarized in Table 9.2. A Hammett plot produces a p value of 2.3 (Fig. 9.22), showing that the mechanism of reaction involves a simple Sn2 displacement by water on the methyl group of the substituted anisole (Fig. 9.23). Finally, the rates of hydrolysis of anisole are found to be substantially faster than that of the more sterically hindered phenetole (Fig. 9.24), consistent with the postulated Sn2 mechanism. 

In view of the high cost of methyl iodide in the above preparation of anisole, and the fact that, unless absolute methanol is used, the ready hydrolysis of the methyl iodide may cause a low yield of the ether, the preparation of anisole may be ad antageously replaced by that of phenetole. I he reaction is not of course a methylation, but is nevertheless of the same type as that used in the preparation of anisole. 

The methoxy group of methoxythiophenes shows a reactivity which, in many respects, differs appreciably from the reactivity of the corresponding anisoles. Thus, in an attempted Hoesch synthesis with 5-methoxy-2-thenylcyanide (167) and phloroglucinol, the methoxy group reacted instead and 5-(2, 4, 6 -trihydroxyphenyl)-2-thenyl cyanide (168) was obtained. 2-Thenyl cyanide reacts normally in the Hoesch synthesis, Likewise, upon acid hydrolysis of the reaction product of 5-methoxy-2-thienyllithium with benzophenone, (169) was obtained instead of the expected substituted methoxythiophene. No defined products could be isolated from the attempted Claisen rear-... 

Bromodesilylation T-methoxy-l-indanones. Cyclization contrary to the normal para-selectivity of anisole derivatives can be effected by temporary use of an ort/jo-trimethylsilyl group introduced by directed orf/io-metallation (11,75). Thus the anisole derivative 1 undergoes bromodesilylation and hydrolysis to provide 2. This product undergoes cyclization to 3 in good yield on conversion to the lithio salt followed by bromine-lithium exchange (8,65-66). 

The combination of ortho metallation and meta nucleophilic acylation was used to prepare a key intermediate in a synthesis of deoxyfrenolicin (42), as outlined in Scheme 11. The complex of anisole is orf/io-metallated with n-butyllithium and quenched with chlorotrimethylsilane the resulting [(o-(tri-methylsilyl)anisole)Cr(CO)3] (43) is then metallated again, converted to the arylcuprate, and coupled with ( )-2-hexenyl bromide to give the complex of l-trimethylsilyl-2-methoxy-3-(2-hexenyl)benzene (44). Addition of the carbanion from the cyanohydrin acetal of 4-pentenal, followed by the standard iodine oxidation and subsequent hydrolysis of the cyanohydrin acetal to regenerate the carbonyl group... 

The observed regioselectively in the introduction of the benzoate group was attributed to ring C in 144 assuming a lower energy twist-boat conformation thereby favouring nucleophilic attack at C(l). Base hydrolysis of benzoate 145 followed by demethylation of the resulting anisole derivative, furnished (+)-pancratistatin with an 11% overall yield from the meso diol. 

The complex of o-substituted anisole 203 is planar chiral, and can be used for diastereoselective generation of two new stereogenic centres in the products. Propargylation and allylation of 203 gave 204 regio- and stereoselectively. Hydrolysis of 204 afforded the cyclohexenone 205, and its intramolecular Pauson-Khand reaction gave 206 diastereoselectively. The two reactions were completely diastereoselective, and the planar chirality in 203 was efficiently transferred to the three new stereogenic centers in 206 [51]. 

Catalytic Rate Constants k and Activation Parameters for Hydrolysis of Chlorosilanes in Anisole at 20°C... 

The reaction appears to be general, although a limited number of examples have been reported. A particularly useful process begins with meta addition to anisole-Cr(CO)3, followed by protonation and hydrolysis of the enol ether unit. The result is a 5-substituted cyclohex-2-en-l-one. This dienol ether can be isolated in high yield before the aqueous hydrolysis. 

Formation of Cyclohexenones. Hydrolysis of the initial enol ether (vinyl ether) formed from Birch reduction of anisole or substituted anisoles under mild acidic conditions leads to P,y-unsaturated cyclohexenones. Under more drastic acidic conditions, these isomerize to the conjugated a, 3-cyclohexenones. Birch reduction of anisoles followed by hydrolytic workup is one of the best methods available for preparing substituted cyclohexenones. ... 

Similar to the hydrolysis of esters, the hydrolysis of ethers occurs at high pressures without the addition of acid catalysts. As for other hydrolysis reactions, high density and the addition of NaCl improves the reaction rate and selectivity of hydrolysis relative to other degradation reactions. Under optimal conditions, the reaction leads only to the respective alcohols. Examples of ethers investigated are methoxynaphthalenes [21], dibenzylether [7, 22], anisols [23], and from cellulose to glucose, fructose and oligomers [24]. 

S-Trimethylsilyl-3-cyclohexenone. This compound is obtained by treatment of anisole with Li-MejSiCl and hydrolysis of the enol ether. Further desilylative acylation and dehydrogenation result in m-acylphenols. 

Complexes of metal + ligand + protein or DNA can also catalyze the Diels Alder cycloaddition or oxidations with hydrogen peroxide. Copper complexes bound to DNA catalyzed the Diels-Alder cycloaddition with up to 99% ee [15, 16], Cu(phthalocyanine) complexed to serum albumin also catalyzed the enantioselective (98% ee) Diels-Alder reaction, but only with very high catalyst loading (10 mol%) and only with pyridine-bearing dienophiles (presumably to complex the copper) [17]. Achiral Cr(III) complexes or Mn(Schiff-base) complexes inserted into the active site of apomyoglobin variants catalyzed the sulfoxidation of thio-anisole with up to 13 and 51% ee, respectively [18, 19]. A copper phenanthroline complex attached to the adipocyte lipid-binding protein catalyzed the enantioselective hydrolysis of esters and amides [20]. 

One of the first eye-catching synthetic applications of arene-chromium chemistry was the synthesis of the sp/ro-sesquiterpenes ( )-acorenone and ( )-acorenone B (rac-7) disclosed by Semmelhack and Yamashita in 1980 [14]. These authors twice exploited the meta-selective nucleophile addition to anisole-Cr(CO)3 derivatives (Scheme 1). Starting from complex rac-1, such a reaction is first used for the regioselective introduction of an acyl sidechain to give 2 after oxidative workup. A few steps later, the nitrile rac-4 (obtained from rac-3 by complexation and separation of the diastereomeric products by preparative HPLC) is deprotonated to form the spiro addition product rac-5, from which the enone rac-6 is obtained after protonation and hydrolysis of the initially formed dienol ether. The final conversion of rac-6 into acorenone B (rac-7) efficiently proceeds over five steps and involves a diastereoselective hydrogenation of an exo-methylene group. 

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