Anisole methylenation

TNT, Glacial acetic acid. Iron powder. Sulfuric acid. Nitric acid, Anisole, Methylene chloride, Magnesium sulfate, Chloroform Potassium chloride, Bleach... 

Aluminum chloride dissolves readily in chlorinated solvents such as chloroform, methylene chloride, and carbon tetrachloride. In polar aprotic solvents, such as acetonitrile, ethyl ether, anisole, nitromethane, and nitrobenzene, it dissolves forming a complex with the solvent. The catalytic activity of aluminum chloride is moderated by these complexes. Anhydrous aluminum chloride reacts vigorously with most protic solvents, such as water and alcohols. The ability to catalyze alkylation reactions is lost by complexing aluminum chloride with these protic solvents. However, small amounts of these "procatalysts" can promote the formation of catalyticaHy active aluminum chloride complexes. 

The selective bromination of a ketone in the presence of another susceptible functional group was achieved in a diterpene synthesis 240). A competing bromination of an anisole ring could be avoided here through the use of a pyrrolidine enamine derivative for activation of the methylene group adjacent to the carbonyl function. 

Benzhydryl 3-carbamoyloxymethyl-7j3-(2-thienylacetamido)-70 -methoxydecephalosporanate (300 mg) in 0.5 ml in anisole and 2.5 ml of trifluoroacetic acid is reacted for 15 minutes at 10°C. The resulting mixture is evaporated at reduced pressure and flushed twice with anisole. The residue is dissolved in methylene chloride and extracted with 5% sodium bicarbonate solution. The aqueous solution is adjusted to pH 1. B with 5% phosphoric acid and extracted with ethyl acetate. The organic solution is dried and evaporated to yield the pure 3-carba-moyloxymethyl-70 -methoxy-7/3-(2-thienylacetamido)decephalosporanic acid, MP 165°C to 167°C. This may then be converted to the sodium salt. 

In a 2-1. three-necked flask fitted with an efficient reflux condenser, stirrer, and pressure-equalizing dropping funnel are placed 216 g. (2.0 moles) of anisole (Note 1) and 400 ml. of methylene chloride (Note 2). The reflux condenser is attached to a drying tower. The solution is brought to reflux temperature with a heating mantle, and 167 ml. (278 g., 2.06 moles) of sul-furyl chloride (Note 3) is added dropwise over a 3-hour period. When the addition is complete, heating is continued for an additional 15 hours (Note 4). 

In a pyrogram of Bisphenol A poly(formal) (6), the peak products are identified as a-methylstyrene, phenol, 4-hydroxy-a-methylstyrene, and isopropyl phenol by Py-GC/MS. These products are identical with the degradation products from Bisphenol A. In addition to the decomposition products of Bisphenol A, 4-isopropenyl anisole is also identified as a product. The pyrograms of Bisphenol AF poly(formal) (7) contain only two major species, pentafluoroisopropenyl benzene (product T) and pentafluoroisopropenyl anisole (product 2 ). They correspond to a-methylstyrene, 4-hydroxy-amethylstyrene from Bisphenol A poly(formal) (6) and are produced by the cleavage of phenylene-oxy bonds and oxy-methylene bonds according to (Scheme 6). 

Chain-Transfer with anisole. The phenomenon of chain-transfer, especially with aromatic compounds, has been extensively investigated for the polymerisation of styrene, but there is only one such study with isobutene [13]. Isobutene (0.1 mole/l) was polymerised by titanium tetrachloride (3 x 10 3 mole/l) in methylene dichloride with a constant, low, but unknown concentration of water in the presence of anisole (0.02 to 0.15 mole/l) over the temperature range -9° to -90°. The reactions were stopped at 10-20 per cent conversion by the addition of methanol. 

In a 500 ml round-bottomed flask equipped with a magnetic stirrer are placed 22 5 g (0 105 mole) of powdered sodium metaperiodate and 210 ml of water The mixture is stirred and cooled m an ice bath (Note 1), and 12 4 g (0 100 mole) of thio-anisole (Note 2) is added The reaction mixture is stirred for 15 hours at ice-bath temperature and is then filtered through a Buchner funnel The filter cake of sodium iodate is washed with three 30-ml portions of methylene chloride The wrater methylene chloride filtrate is transferred to a separatory funnel, the lower methylene chloride layer is removed, and the water layer is extracted with three 100-ml portions of methylene chloride The combined methylene chloride extracts are treated with activated carbon (Note 3) and dried over anhydrous sodium sulfate (Note 4) The solvent is removed at reduced pressure to yield 13 6-13 9 g of a slightly yellow oil (Note 5) which crystallizes on cooling The crude sulfoxide is transferred to a 25 ml distillation flask with the aid of a small amount of methylene chloride After removal of the solvent, a pinch of activated carbon is added to the distillation flask (Note 6) Simple vacuum distillation (Note 7) of the crude product through a short path still affords 12.7-12 8 g (91%) of pure methyl phenyl sulfoxide, b p 78-79° (0 1 mm ), m p. 33-34° (Notes 8 and 9)... 

Equivalent protons. All hydrogens which are in identical environments have the same chemical shift and therefore absorb at the same frequency they are said to be chemically equivalent. This can arise in two ways. Firstly, the protons are equivalent if they are bonded to the same carbon atom which is also free to rotate. For example, the three protons in a methyl group are equivalent and appear as a singlet (see the spectra of toluene, anisole or acetophenone above), and the two protons of a methylene group, provided that it can rotate freely, are identical and appear as a singlet (see the spectrum of phenylacetic acid above) frequently this is not the case with methylene groups in cyclic systems where rotation is restricted. 

The 8-oxo-7-phenylacetylamino-5-thia-l-aza-bicyclo[4.2.0]oct-l-ene-2-carboxylic acid benzhydryl ester is reacted with phosphorus pentachloride/pyridine reagent in methylene dichloride, and the reaction mixture is thereafter cooled to -35°C and treated with methanol to produce hydrochloride of 7-amino-8-oxo-5-thia-l-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester. This hydrochloride is reacted with 4-(3-aminothiophen-2-yl)-5-oxohex-3-enoic acid 3-methylbut-2-enyl ester. Then 7-[2-(2-benzoylamino-thiazol-5-yl)(3-tert-butyl-4,4-dimethylpent-2-enoxycarbonyl)-pent-2-enoylamino]-8-oxo-5-thia-l-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid synthesized is reacted with aluminum chloride in anisole and diluted hydrochloric acid and then with dimethylmalonate to give 5-thia-l-azabicyclo(4.2.0)oct-2-ene-2-carboxylic acid, 7-(((2Z)-2-(2-amino-4-thiazolyl)-4-carboxy-l-oxo-2-butenyl)amino)-8-oxo-, (6R,7R)- (Ceftibuten). 

Perot et al. [7] in collaboration with Rhodia have studied the deactivation of industrial catalysts HBEA and HY during the acylation of veratrole and anisole. After reaction, the spent catalysts were extracted with methylene chloride. This Soxhlet extraction makes possible the elimination of compounds that were not strongly adsorbed on the zeolites. The composition of the residue obtained after evaporation of methylene chloride was practically the same as that of the reaction mixture at the end of the experiment. By this extraction procedure, approximately 80% of the compounds remaining on the catalysts after reaction were recovered. After Soxhlet extraction, the catalyst samples were recovered and dissolved with hydrofluoric acid. The organic compounds released by the catalysts were extracted again by methylene chloride and, after evaporation of solvent, the residues contained di- and triketones as well as cyclization compounds, the structures of which are presented in Scheme 14.1. 

Zinc oxide, an inexpensive and commercially available inorganic solid, can be utilized as an efficient catalyst in the Friedel-Crafts acylation of activated and unactivated aromatic compounds with acyl chlorides at room temperature for 5 to 120 min (Table 4.14). Acylation is claimed to occur exclusively at the para-position of the monosubstituted aromatic compounds. The catalyst can be recovered and reused, after washing with methylene chloride, for at least two further cycles, showing quite similar high yield (-90%) in the model benzoylation of anisole. Mechanistically, it seems that zinc chloride can be the true catalyst, generated in situ by the reaction of zinc oxide with hydrogen chloride. 

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. 

Weinreb has introduced the rert-butylsulfonyl (Bus) group for protection of primary and secondary amines <97JOC8604>. For instance, reaction of indoline (104) with readily prepared /err-butylsulfinyl chloride affords the corresponding sulfinamide 105 which can be oxidized with either m-chloroperbenzoic acid or RuCl3(cat)/NaI04 to the fer/-butylsulfonamide 106. Such N-Bus protected secondary amines can be cleaved with 0.1 N triflic acid in methylene chloride or with neat TFA/anisole overnight. 

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