Alkylation 2-alkylated hydroquinones

Alkylations of nitrophenylacetates, indole, and methyl benzylidene glycinate under dry conditions induced by microwaves have been studied, leading to the synthesis of arenes (66) linked by a long hydrocarbon chain (Abramovitch et al., 1995). Kumar et al. (1999) reported the enviromnental-friendly process for the synthesis of 2-alkylated hydroquinones (67) under microwave irradiation using 1,4-cyclohexanedione and aldehydes catalyzed by KF-AI2O3. An attractive methodology using microwave irradiation is described by Vanelle et al. (1999) for reactions of... 

Kumar, H.M.S., Subba Reddy, B.V., Reddy, E.J., and Yadav, J.S. 1999. Microwave-assisted eco-friendly synthesis of 2-alkylated hydroquinones in dry media. Green Chemistry, l-.Ul-Al. 

Figure 9.2 Stabilization of an alkylated hydroquinone by electron delocalization.

The N-oxides of isoquinolines have proved to be excellent intermediates for the preparation of many compounds. Trialkylboranes give 1-alkyl derivatives (147). With cyanogen bromide in ethanol, ethyl N-(l- and 4-isoquinolyl)carbamates are formed (148). A compHcated but potentially important reaction is the formation of 1-acetonyLisoquinoline and 1-cyanoisoquinoline [1198-30-7] when isoquinoline N-oxide reacts with metbacrylonitrile in the presence of hydroquinone (149). Isoquinoline N-oxide undergoes direct acylamination with /V-benzoylanilinoisoquinoline salts to form 1-/V-benzoylanilinoisoquinoline [53112-20-4] in 55% yield (150). A similar reaction of AJ-sulfinyl- -toluenesulfonamide leads to l-(tos5larriino)isoquinoline [25770-51-8] which is readily hydrolyzed to 1-aminoisoquinoline (151). 

The N,]S -dialkyl-/)-PDAs are manufactured by reductively alkylating -PDA with ketones. Alternatively, these compounds can be prepared from the ketone and -lutroaruline with catalytic hydrogenation. The /V-alkyl-/V-aryl- -PDAs are made by reductively alkylating -nitro-, -nitroso-, or /)-aminodipheny1 amine with ketones. The AijAT-dialkyl- PDAs are made by condensing various anilines with hydroquinone in the presence of an acid catalyst (see Amines-aromatic,phenylenediamines). 

Another positive-working release by cyclization, illustrated by equation 5, starts with an immobile hydroquinone dye releaser (8), where R = alkyl and X is an immobilizing group. Cyclization and dye release take place in alkaU in areas where silver haUde is not undergoing development. In areas where silver haUde is being developed, the oxidized form of the mobile developing agent oxidizes the hydroquinone to its quinone (9), which does not release the... 

Because they are acrylic monomers, alkyl cyanoacrylate esters still require the addition of radical polymerization inhibitors, such as hydroquinone or hindered phenols, to prevent radically induced polymerization over time [3j. Since basic initiation of alkyl cyanoacrylate monomers is the predominant polymerization mechanism, large quantities of free radical inhibitors can be added, with little or no effect on adhesive performance. 

As shovm above, the attachment of the aromatic ring to the carbon chain bearing the basic nitrogen may be accomplished through an ester or an amide configured in either direction. A simple ether linkage fulfills this function in yet another compound that exhibits local anesthetic activity. Thus, alkylation of the mono potassium salt of hydroquinone with butyl bromide affords the ether (77) alkylation of this with w-C3-chloropropyl)morpholine affords pramoxine (78)... 

Alkylation of the monobenzyl ether of hydroquinone 34 with mesylate 35, gives ether 36. Hydrogenolytic removal of the benzyl group gives phenol 37. This affords cicloprolol (38) when subjected to the standard alkylation scheme 17]. In much the same vein, alkylation of g-hydroxy-phenylethanol 39, obtainable from the corresponding phenylacetic acid, with epichlorohydrin... 

Ni(0)-mediated homocouplings of 2-subslituted l,4-phcnylenebis(triflate)s have been reported by Percec et al. [15] to provide substituted poly(/ -phenylene)s 7 containing alkyl, aryl or ester substituents in the 2- and 3-positions of the 1,4-phenylcnc skeleton. This method of preparation appears to be broad in scope, especially due to the ease of preparation of the bis(lriflatc) monomers starting from the corresponding hydroquinone derivatives. 

Hydroquinone is another safe alternative to hydrazine and was originally covered under a Betz patent. Related compounds and their alkyl-substituted derivatives were similarly patented, including o- and /7-diamino and aminohydroxybenzenes. 

Lithiochloromethyl phenyl sulfoxide 99 was found to react with aryl or alkyl halides in the presence of one equivalent of hexamethylphosphoramide to afford alkylated products 100 in high yields135. Thermal decomposition of these products in the presence of a catalytic amount of hydroquinone in xylene gave the corresponding vinyl compounds 101. 

Clay-supported heteropoly acids such as H3PW12O40 are more active and selective heterogeneous catalysts for the synthesis of MTBE from methanol and tert-butanol, etherification of phenethyl alcohols with alkanols, and alkylation of hydroquinone with MTBE and tert-butanoi (Yadav and Kirthivasan, 1995 Yadav and Bokade, 1996 Yadav and Doshi, 2000), and synthesis of bisphenol-A (Yadav and Kirthivasan, 1997). 

The continuing interest in bioreductive alkylation is largely due to the clinical success of mitomycin C and the low reduction potentials observed in many tumors.9 The low reduction potentials favor the quinone to hydroquinone conversion necessary for bioreductive alkylation. Hypoxia due to low blood flow3 and/or the unusually high expression of the quinone two-electron reducing enzyme DT-diaphorase in some histological cancer types10-14 contribute to the tumor s tendency to reduce quinones. 

For over 35 years, the quinone methide species has been invoked as a reactive intermediate in bioreductive alkylation and in other biological processes.8 29 Generally, there is only circumstantial evidence that the quinone methide species forms in solution. Conceivably, the O-protonated quinone methide (i.e., the hydroquinone carbocation) could be the electrophilic species. If so, bioreductive alkylation may simply be an SN1 reaction. Also, there are questions concerning the mechanism of quinone methide... 

Alkylation reactions by the iminium methide species are well known in the mitomycin and mitosene literature 4,49,51-53 and are largely responsible for the cytotoxicity/antitumor activity of these compounds. As illustrated in Scheme 7.8, the electron-rich hydroquinone intermediate can also be attacked by the iminium ion resulting in either head-to-head or head-to-tail coupling. The head-to-head coupling illustrated in Scheme 7.8 is followed by a loss of formaldehyde to afford the coupled hydroquinone species that oxidizes to the head-to-head dimer upon aerobic workup. Analogous dimerization processes have been documented in the indole literature, 54-56 while the head-to-tail mechanism is unreported. In order to... 

The redox system consists of pyrene or 9,10-phenanthrene quinone as oxidant and an alkyl ester of 3,3, 3"-nitrilopropionic acid as reductant.121 This system deactivates oxidation by bisimidazole when irradiated at 380-550nm, since the quinone is reduced to hydroquinone and thus stabilizing the previously generated dye image.122,123... 

A possible mechanism proposed by Kuivila was based on the fact that retardation by hydroquinone has been observed 72) (see however 73)) and that optically active alkyl halides RX have been transformed into racemic RD 72). 

Another class of DNA alkylating agents, the Mitomycins, proved to be most promising in clinical trials. Among these, mitomycin C, shown in Fig. 6.1, exhibits significant anti-tumor activity. Its mechanism of activation consists of a complex bioreductive process. The first step is the reduction to hydroquinone, followed by a loss of methanol. This reaction fa-... 

The processes of oxidation of cyclohexadiene, 1,2-substituted ethenes, and aliphatic amines are decelerated by quinones, hydroquinones, and quinone imines by a similar mechanism. The values of stoichiometric inhibition coefficients / and the rate constants k for the corresponding reactions involving peroxyl radicals (H02 and >C(0H)00 ) are presented in Table 16.3. The/coefficients in these reactions are relatively high, varying from 8 to 70. Evidently, the irreversible consumption of quinone in these systems is due to the addition of peroxyl radicals to the double bond of quinone and alkyl radicals to the carbonyl group of quinone. 

The method described in this preparation of mesitoic acid avoids the preparation of bromomesitylene,13 and the yield of acid is essentially the same as that from the two-step synthesis.2-13 This procedure appears to be general and can be used to prepare such acids as a- and /3-naphthoic acids,14 cumenecarboxylic acid, 2,5-dimethylbcnzoic acid, and durenecarboxylic acid. Carboxylic acids could not be obtained from benzothiophene, vera-trole, -dimethoxybenzene, and ferrocene under the conditions of this reaction. Although there has been no exhaustive study, this procedure is probably applicable to a variety of aromatic compounds, especially alkylated aromatics. Aromatic compounds which readily undergo oxidation, e.g., ferrocene, catechol, and hydroquinone, do not lend themselves to this method. 

Antioxidant. Substances that retard or inhibit autoxidation at moderate temperatures and pressures. Commonly Icnown, commercial antioxidants are aromatic amines, alkylated phenols, cresols, and hydroquinones. 

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