Methoxylation of furans

Dialkoxylations Investigated in Micro Reactors Organic synthesis 59 [OS 59] Di-methoxylation of furan... 

Anodic hydroxylation/methoxylation of furans has an exact chemical counterpart in the well-known bromine/methanol reaction, and the choice of method is not always easily made. One can compare the two methods particularly easily in syntheses of the flavoring component, the pyrone maltol 121, from the furan 122 since one group used the electrolytic method299 and another the chemical method.300... 

In a similar manner, bromine has been employed as an oxidant for glucose to calcium gluconate [132] and for the methoxylation of furan [133] (Eq. 11). 

The electrochemical methoxylation of furans to give the corresponding dimethoxy-dihydrofurans was discovered by Clauson-Kaas 205 in 1955. This reaction is now carried out industrially by BASF 206> and Otsuka 192). 

The direct electrochemical methoxylation of furan derivatives represents another technically relevant alkoxylation process. Anodic treatment of furan (14) in an undivided cell provides 2,5-dimethoxy-2,5-dihydrofuran (15). This particular product represents a twofold protected 1,4-dialdehyde and is commonly used as a C4 building block for the synthesis of N-heterocycles in life and material science. The industrial electroorganic processes employ graphite electrodes and sodium bromide which acts both as supporting electrolyte and mediator [60]. The same electrolysis of 14 can be carried out on BDD electrodes, but no mediator is required The conversion is performed with 8% furan in MeOH, 3% Bu4N+BF4, at 15 °C and 10 A/dm2. When 1.5 F/mol were applied, 15 is obtained in 75% yield with more or less quantitative current efficiency. Treatment with 2.3 F/mol is rendered by 84% chemical yield for 15 and a current efficiency of 84% [61, 62]. In contrast to the mediated process, furan is anodically oxidized in the initial step and subsequently methanol enters the scene (Scheme 7). 

The effectiveness of RE and PC electrochemical reactors for methoxylation of furan was examined by Thomas et al. (1988). The performance of various types of reactors is compared in Table XXIX. As shown, both RE and PC with cathode spinning gave better performance than a capillary gap cell. For the pump cell, the results differ depending on whether the cathode is spinning or... 

Fig. 5.6 Anodic methoxylation of furan (7). Reagents and conditions (a) graphite electrodes 15% furan in MeOH, 1.2% NaBr, <10°C, 12Adm-2, yield = 79%, select. 96%, X = 82% at 1.6 F mol-1, current efficiency = 96% (b) BDDE 8% furan in MeOH, 3% Bu4N+BF4-, 15°C, 10 Adm2, yield = 75% at 1.5Fmol-1, current efficiency = 99% yield = 84% at 2.3Fmol-1, current efficiency = 74%...

Another example of different electrode mode of action is the methoxylation of furan (7) to 2,5-dimethoxy-2,5-dihydrofuran (8, DMD), as a masked 1,4-dialdehyde an intermediate for N-heterocycle synthesis and life-science products (Fig. 5.6). On graphite electrodes, this reaction needs a halide salt-like sodium bromide both as supporting electrolyte and mediator (Degner et al. 1978). If the same reaction is carried out on a BDD electrode, a mediator is not needed (Reufer et al. 2004). 

One of the earliest synthetic reactions in which the halide anion was used as a mediator is the anodic methoxylation of furan in the presence of O.OS equiv. of ammonium bromide, though the reaction has not been termed a mediated oxidation (equation 64). ... 

Ethers can be obtained most easily by alkylating the enols as noted above, from cycloadditions to alkoxyisoxazoles (Section II,H, Part I), and from 2,2-84 or 2,5-dimethoxydihydrofurans, the latter being easily accessible by the methoxylation of furans (Sections VI,A,1 and VI,B,1, Part I) a method that has been neatly adapted to a synthesis of 3-bromo-2-methoxyfuran.8 ... 

Different electro-organic reaction systems have been studied. The anodic reactions investigated are mainly the four-electron methoxylation of 4-methoxytoluene [6, 7, 11, 12] and the two-electron methoxylation of furan to 2,5-dimethoxy-2,5-dihydrofuran [10], but also other methoxylation and acetoxylation reactions [11]. Methoxylation reactions are performed in methanol as a solvent, whereas acetoxyla-tions are performed in acetic add. Moreover, Kiipper et al. [7] reported the anodic two-electron decarboxylation of sodium glucanate in an aqueous medium. The cathodic... 

C. Belmont, H. H. Girault, Coplanar interdigitated band electrodes for electrosynthesis Part 2. Methoxylation of furan, J. Appl. Electrochem., 1994, 24, 719-724. 

Various anodic methoxylation reactions are applied in the chemical industry using a supporting electrolyte. Accordingly, several investigations using SPE technology also deal with methoxylations. The paper [6] and the alkoxylation of V-alkylamides were mentioned previously. Another example is the anodic di-methoxylation of furan where yields of up to 80 % of 2,5-dimethoxy-2,5-dihydrofuran have... 

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