Furans methoxylation

The conversion of furans by oxidative acetylation or methoxylation to 2,5-diacetoxy- or 2,5-dimethoxy-2,5-dihydrofurans respectively, and their subsequent hydrogenation to the corresponding tetrahydrofurans, provides a useful source of protected 1,4-dicarbonyl compounds capable of conversion inter alia into the other five-membered heterocycles [Pg.142]

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). 

Urethanes can be anodically methoxylated, as other amides they may react with furan in the presence of an acid. Anodic methoxylation of the furan gives a dimethoxydihydrofuran in the Clauson-Kaas reaction1 on acid hydrolysis 3-hydroxypyridines (51) are obtained114 [Eq. (46)]. 

Various 3-methylcoumarilic acids substituted in the benzene ring by alkyl or methoxyl groups have been thus prepared, then decarboxylated to the corresponding benzofurans,10 208 e.g., 3-methyl-4,7-dimethoxy-benzofuran 2-naphthol233 leads to 3-methylnaphtho[2,l-6]furan (79), guaiacol to ethyl 7-methoxy-3-methyl coumarilate.234... 

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). ... 

The 7c-excessive character of furan facilitates single-electron oxidation however, the cation-radicals produced from simple furans are not, in general, persistent. The mediation of 2,5-dimetliylfuran cation-radical (1) has been proposed in anodic oxidations yielding methoxylated, cyanomethoxylated, and acyloxylated products.Although not specifically implicated, cation-radicals may be involved in very similar oxidative reactions. ... 

The anodic methoxylation of aromatic compounds such as naphthalene [41], anthracene [42], alkylbenzenes [31,43], phenols [44-46], anisoles [33,47-54] and other alkoxyben-zenes [53], methoxynaphthalenes [33], methoxyanthracenes [50,54], inden-l-ones [55], / a/r/-substituted anilides [56] and heterocyclic compounds, such as furans [57], thiophenes [58], and pyrroles [59], has received considerable attention. 

Since furans are anodically 2,5-dimethoxylated in high yields to give the corresponding cis-and rra -2,5-dimethoxy-2,5-dihydrofurans, which are regarded as equivalents to the E and Z unsaturated 1,4-dicarbonyl compounds, this anodic methoxylation is important and useful in synthetic chemistry. 

The stereochemistry (cis and trans) of the methoxylated furans has been examined [309]. In most cases the rrawj -isomers are the major products. 

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 ... 

The anodic oxidation of furans in methanol was also carried out without an intentionally added electrolyte (Figure 12.11) [38, 39]. 2,5-Dimethoxy-2,5-dihydro-furan was obtained in 98% yield. The anodic methoxylation and acetoxylation of various organic compounds was also achieved using this system. 

Furans continue to be useful synthons for pyridazine syntheses. A detailed investigation of the reaction between ethyl 2-methoxy-2-methyl-3-oxofuran-4-carboxylate (47) and hydrazines revealed that, depending upon reaction conditions, compound 49, a mixture of 48 and 49 or, in addition to these, also 50, is obtained.172,173 Similarly, ethyl 5-nitrofuran-3-carboxylate and hydrazine yield a pyridazine, probably by addition, ring opening of the furan, and recyclization [Eq. (12)].174 Another synthesis involves electrolytic methoxylation of a furan derivative and subsequent treatment with hydrazine.175... 

---