1,2-Dimethoxybenzene, reactions with

The lithiated dimethoxybenzene reaction with 2,2-dipyridyl disulfide produced 2,5-dimethoxyphenyl 2-pyridyl sulfide which distilled at 135-150 °C at 0.4 mm/Hg and could be recrystallized from cyclohexane containing 2% EtOH to give aproduct thatmelted at 66-67.5 °C. Anal. (CnHnNO,S) C,H. This would have produced 2,5-dimethoxy-4-(2-pyridylthio)phenethylamine (2C-T-10) but it was never pursued. 

Br, 2,600 5-C1, 2,700 5-CN, 260277,277a. A good correlation of the substituted dimethoxybenzene data with the Hammett equation was obtained with p = —4.0 this value was taken to further confirm the heterolytic nature of the rate-determining step. The incursion of an apparently homolytic reaction was detected if the aromatics were distilled from diethyl ether, anomalously high but quite reasonably... 

Some fluorescent derivatives are specific to certain functional groups. For example, peptides containing tyrosine may be detected by adding a —CHO group to the tyrosine of the peptide by formylation with chloroform in an alkaline medium, followed by reaction with 1,2-diamino-4,5-dimethoxybenzene. The derivatives thus formed are fluorescent and can be detected at an excitation wavelength of 350 nm and an emission wavelength of 425 nm (95). 

Since trimethylsilylarenes can be prepared by metallation of the arene followed by treatment with chlorotrimethylsilane, this provides an alternative route into a range of difficult substitution patterns. For example, the ortho/para directing effects of the methoxy groups in 1,3-dimethoxybenzene 75 direct the electrophile to the 4-position. However, lithiation of 1,3-dimethoxybenzene takes place at the 2-position. Reaction with chlorotrimethylsilane then gives the 2-trimethylsilyl compound 76, which undergoes ipso substitution with the electrophile to give the 1,2,3-trisubstituted product 77 (equation 39)101,102. 

As would be expected, the presence of a second electron-donating group in 1,4-dimethoxybenzene appreciably increases its rate of reaction with HGeCl3 in comparison with anisole. With a threefold molar excess of HGeCl3, the reaction at room temperature is complete after a period of 4 to 5 hours and leads to the formation of 1,4-dimethoxy-l,2,4-tris(trichlorogermyl)cyclohexane 49 in 85% yield (equation 42)88. 

Dinitro-6-phenyliodonium phenolate (146) is a stable iodonium zwitterion484. It reacts under photolytic conditions with various alkenes, alkynes and aromatic compounds to afford 2,3-dihydrobenzo[ ]furans, benzo[6]furans and 6-aryl-2,4-dinitrophenols. The mechanism involves hypervalent iodine compounds (iodinanes, 147) and is illustrated for the reaction with an aromatic compound (equation 127). Compounds 148 are the major products when ArH = PhH, PhOCH3 or 1,4-dimethoxybenzene. With furan and thiophene, 149 is the principal product. The reaction does not proceed with chlorobenzene and nitrobenzene. 

A series of azophenol acerands 4 was prepared by condensation of crowned benzoquinones 10 with 2,4-dinitrophenylhydrazine in ethanol [7b], The quinone was derived from p-methoxyphenol (6) as shown in Scheme 1 [8]. By bis(hy-droxymethylation) (67% yield of 6, followed by methylation (92%) of the phenol group and Williamson-type reaction with ditosylates of oligoethyleneglycol in the presence of sodium hydride, crowned 1,4-dimethoxybenzene 9 was obtained in reasonable yields. Oxidative demethylation of 9 with ceric ammonium nitrate (CAN) in aqueous acetonitrile at 50 °C gave the desired crowned benzoquinones 10 in good yields. 

The synthesis of a typical compound containing two units of dihydrobenzoin is shown as an example in Scheme 7 [26]. Reaction of 2,6-bis(bromomethyl)l,4-dimethoxybenzene 41 with the dibutyltin derivative of optically active dihydrobenzoin 59 yields a chiral podand 60 in 63%. Cyclization of 60 with the ditosylates of oligoethylene glycols, followed by oxidation with CAN and treatment with dinitrophenylhydrazine, affords the desired chiral dyed acerand 53. Some chiral azophenol acerands 51-58 are synthesized in a similar manner. 

In photolysis of ketones CIDNP studies have confirmed that the Norrish type I split occurs predominantly from a phototriplet state (32,38,118), although some of the reactions with aliphatic ketones exhibit polarization involving both the excited singlet and the triplet (47,118) states as well as the postulated exci-plex intermediates (71). An exciplex mechanism has also been postulated in the CIDNP observation of the photolysis of tri-fluoroacetophenone with dimethoxybenzene in acid solutions (117). 

When (253) reacts with phosgene the 1-acyl chloride product (254) can react with amines to give amides (79LA1756X while in a further transfer reaction with ketones the compounds (255) and (256) are produced (Scheme 146) (80H(14)97). Acylation of aromatic hydrocarbons using 1-acylimidazoles in the presence of trifluoracetic acid gives high yields provided that the aryl compounds are electron rich, e.g. p-dimethoxybenzene, thiophene, anisole <80BCJ1638). 

Inspection of the structures of caffeine, acetyisalicyiic acid, and acet>-aminophen reveals that one is a base, one a strong organic acid, and one a weak organic acid. One might be tempted to separate this mixture using exactly the same procedure as employed in Chapter 8 to separate benzoic acid, 2-naphthol, and 1,4-dimethoxybenzene, i.e., dissolve the mixture in dichloromethane remove the benzoic acid (the strong acid) by reaction with bicarbonate ion, a weak base then remove the naphthol, the weak... 

The third compound studied is the 4-thio analog of mescaline, 4-methylthio-3,5-dimethoxyphenethylamine. This was prepared (see scheme II) by the reaction, of lithiated m-dimethoxybenzene with dimethyldisulfide to form 2,6-dimethoxythioanisole. This underwent bromination uniquely adjacent to the methoxy group, and the resulting bromodimethoxythioanisole underwent a smooth benzyne reaction with acetonitrile to form the benzyl cyanide shown, which was reduced to the desired end product (3) with aluminum hydride in THF. 

Dimethoxybenzene reacts with A -methylenemoipholinium chlwide in acetonitrile to afford the Mannich product, characterized as the hydrobromide, in 66% yield. The analogous reaction using the pyrrolidinium salt is shown in equation (21). Ferrocene gives low yields of products, for example with... 

Acylation of anisole with A AN is carried out in a mixture of GALDEN SV 135, a suitable fluorous solvent, and chlorobenzene in the presence of hafnium tetra[bis(perfluorooctanesulfonyl)amide] (1% mol) at 70°C-120°C for 1 to 5 h, giving para-methoxyacetophenone in 80% yield and 100% selectivity. It is significant to underline that aluminum chloride gives the mentioned product in only 2% yield under the present mild reaction conditions. The catalyst can be very easily recycled by directly reusing the lower fluorous catalytic phase in the successive reaction with another mixture of reactants, affording the product more than three times without decrease in catalytic activity. The catalytic process can be applied to dimethoxybenzenes and mesitylene with both aliphatic and aromatic acyl chlorides and anhydrides (80%-97% yield). Benzoylation of toluene gives para-methylbenzophenone in 35% yield. 

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