Phenetole preparation

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. 

This ether, C iHg. O. CgHg, is known as phenetole. It is a fragrant liquid boiling at 172°, and is prepared in a similar manner to the methyl ether. 

Heating pyridine-2,3-dicarboxylic acid anhydride with l-ethyl-2-methylindole has been claimed to yield solely the pyridine-2-carboxylic acid, albeit in low yield. This then clearly reacts with Af,A/-diethyl-3-toluidine in acetic anhydride to give the 7-azaphthalide. This is surprising in view of a later report70 in which a one-pot process has been described. Heating pyridine-2,3-dicarboxylic anhydride, prepared in situ, with the indole and subsequent reaction with 3-/V,/V-diethylamino-phenetol under identical conditions to those used in Scheme 8 (but without intermediate isolations) produced a 20 1 mixture of the 4- and 7-azaisomers 16 and 17. It appears that in the previous report the major intermediate isomer, the pyridine-3-carboxylic acid, has not been isolated. 

In an analogous way phenetole, is prepared from phenol by the action of diethyl sulphate. 

Of the substituted phenol ethers the amino-derivatives of anisole (anisidine) and phenetole (pkenetidine) may be mentioned. They are prepared from the nitrophenols by alkylation and subsequent reduction of the nitro-group. 

When 2 -methoxy-2-biphenylamine is diazotized in fluoroboric acid, an 85% yield of solid 2 -methoxy-2-biphenylyldiazonium tetrafluoroborate is produced. On heating in dry benzene, this salt loses nitrogen and provides 0-methyldibenzofuranium tetrafluoroborate as an unstable solid. The latter salt, on account of the low basicity of dibenzofuran, reacts with a range of nucleophiles that undergo methylation with the release of dibenzofuran. Pyridine and pentachloropyridine are N-methylated, benzo[fc]thiophene is S-methylated, and tetrahydrofuran and phenetole are 0-methylated. ° Thus it is no surprise that diazotization of 2 -methoxy-2-biphenylamine, followed by boiling of the diazonium salt in acidic solution, provides dibenzofuran in 90% yield.The scope of this method of dibenzofuran synthesis (Scheme 18) has been little explored probably because of the difficulty of preparing the requisite biphenyls, which is usually accomplished by a crossed Ullmann reaction. A similar synthesis of xanthones from 2-amino-2 -methoxybenzophenones is known. ° ... 

These compounds are suggested if sulphur is present. If nitrogen is also present the compound may be an aminosulphonic acid. The infrared spectrum will show absorption at 3400-3200 cm -1 (OH str.) and 1150 and 1050 cm-1 (S=0 str. in a sulphonic add) or at 1090cm-1 (S=0 str. in a sulphinic acid). For derivative preparations for sulphonic acids see Section 9.6.26, p. 1284. The presence of an aromatic sulphinic add may be further confirmed by dissolving in cold concentrated sulphuric add and adding one drop of phenetole or anisole when a blue colour is produced (Smiles s test), due to formation of a para-substituted aromatic sulphoxide. The reaction is ... 

Hydrolysis of chloronitro compounds. The chlorine atom in chlorobenzene and in its homologues becomes reactive after one or more nitro groups have been introduced into the ring. This is used widely in the preparation of nitrophenols and their ethers. The preparation of dinitrophenol, dinitroanisole and dinitro-phenetole may serve as a classical example (see Chapter XVI). 

The following compounds are prepared in a similar manner, substituting toluene, anisole, phenetole, and diphenyl ether, respectively, for benzene ... 

Allj-ether (ether = THF, tetrahydropyran, oxetan, 2-MeTHF, Et20, Bui O, anisole, or phenetole), and All3,SEt2 adducts may be prepared by direct reaction of the components. H n.m.r. parameters were listed. ... 

Fission of aryl ethers can also be effected by metallic sodium or potassium. For instance, diphenyl ether, which is one of the most resistant ethers, is decomposed by liquid potassium-sodium alloy at room temperature.38 Weber and Sowa have cleaved 4,4 -disubstituted diphenyl ethers into benzene and phenol derivatives by sodium in liquid ammonia.39 Diallyl ether is converted by sodium dust at 35° into allylsodium and sodium allyl oxide, which provides a suitable method for preparation of allylsodium.3 7a Anisole, phenetole, benzyl phenyl ether, and diphenyl ether give the phenols in 90% yield, without by-products, when boiled with sodium or potassium in pyridine.40... 

The second problem prepares ethoxybenzene (21 phenetole) from benzene, and the retrosynthetic analysis is 21 19 => 42 benzene. Because 21 is an ether, the most likely precursor is phenol (19), which is prepared from aniline (23) via the diazonium salt. Aniline is derived from nitrobenzene (42), which is prepared directly from benzene. Therefore, the synthesis is that shown in the following illustration. 

The optimum conditions for the preparation of phenetole complexes of higher molecular weight trialkylaluminiums have been examined, reaction (4). Alane-... 

Preparation by reaction of 3,5-dinitrobenzoyl chloride with phenetole in the presence of aluminium chloride in carbon disulfide, first between 0° and 5° for 8.5 h, then at r.L overnight (60%) [903]. 

Preparation by dealkylation of 3-bromo-4 -ethoxy-benzophenone (SM) with hydrobromic acid (d = 1.49) in boiling acetic acid for 2 days. SM was obtained by action of m-bromobenzoyl chloride with phenetole in carbon disulfide in the presence of aluminium chloride at 55° (80%, m.p. 79°5). -Refer to Chem. Abstr., 17, 3497 (1923) . m.p. 171° Spectra (NA). 

Preparation by acylation of phenetole with m-nitrobenzoyl chloride in ethyl ether in the presence of alumininm chloride, then dealkylation of the 4-ethoxy-3 -nitrobenzophenone so formed with the same catalyst [141], in boiling carbon disulfide (60-70°) for 8 h [619] according to [139]. Preparation by Fries rearrangement of phenyl m-nitrobenzoate with alumininm chloride [897] without solvent at 120° or at 160° for 2 h (32%) [958]. 

Preparation by reaction of m-(trifluoromethyl) benzoyl fluoride with phenol in hydrofluoric acid at 100° for 6 h under 5 atmospheres (92%) [978]. - Preparation by reaction of m-(trifluoromethyl)benzoyl chloride with phenetole in the presence of aluminium chloride in carbon disulfide between 0° and 5°, then at r.t. for overnight (21%) [903]. m.p. 144-145° [903] Spectra (NA). 

Preparation by reaction of propionyl chloride with phenetole in the presence of aluminium chloride in carbon disulfide [6722]. 

Trimethylanisole reacts with excess chlorosulfonic acid to give 4-methoxy-2,3,6-trimethylbenzenesulfonyl chloride this compound is used as a reagent for the protection of amino groups in peptide synthesis. Phenetole (ethyl phenyl ether, 187 R = Et), by reaction with chlorosulfonic acid (two equivalents) in chloroform yields the 4-sulfonyl chloride ° which is used in the preparation of heat sensitive recording materials. ... 

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