Methoxylation reaction

Oxidative Animation of Nitrones to a-Amino-Substituted Nitroxyl Radicals Similar to the oxidative methoxylation reaction, oxidative animation of 4H -imidazole TV-oxides, in amine saturated alcohol solutions, give stable nitroxyl (282), nitronyl nitroxyl (283), imino nitroxyl (284) and (285) radicals with the amino group at the a-carbon atom of the nitroxyl group (Scheme 2.107) (520, 521). The observed influence of substituents on the ratio of animation products at C2 and C5 atom is close to the ratio observed in the previously mentioned oxidative methoxylation reaction. It allows us to draw conclusions about the preference of the radical cation reaction route. 

In nonaqueous media, carbon (graphite) frequently is an optimal anode material, for example, for methoxylation reactions, even in an industrial scale (capillary gap cell, see Fig. 12). It shows an appreciable overvoltage for the oxidation of methanol compared to platinum. 

The photocyanation of 1-nitroazulene was accompanied by a dark reaction and was thus less suitable for mechanistic studies than the methoxylation. 2-Acetonaphthone (Et=59 kcal mole i) and 2-naphthophenone ( t=60 kcal mole i) were found to be efficient sensitizers for the disappearance of 1-nitro azrdene in the methoxylation reaction. The measured rate of product formation, however, seemed to be much lower than the rate of starting material disappearance. This effect has been attributed to sensitized decomposition of the product 104)... 

The stereochemical course of fluorination-methoxylation reactions in the case of cyclic phenyl-substituted alkenes 23 depends strongly on the structure of the alkene.95... 

The same technique can be applied to regioselectively prepare 4-alkoxy substituted azetidinones. Non-silylated azetidinones have oxidation potentials, which are too high for this process. Introduction of a silyl group lowers these potentials, rendering the reaction easier and more regiospecific. Note that in the case of /V-benzyl azetidinones, the methoxylation reaction occurs also at the benzylic position.12213 355... 

Kiipper et al. carried out a methoxylation reaction of 4-methoxytoluene in an electrochemical microreactor in which a glass carbon anode and a stainless steel cathode were separated by a microchannel foil 25 pm thick [54], The chemical resistance of the microchannel foils was very important because of the evolution of hydrogen and oxygen gases and the strong pH shifts during electrolysis. PEEK was found to be the most robust material. They also observed that selectivity of the oxidation of 4-methoxytoluene in acidified methanolic solution (pH 1, sulfuric acid) was influenced by the current density and flow rate. 

Scheme 6 Potential pathway of BDD mediated methoxylation reaction of 4-ter/-huty [toluene...

The stoichiometry indicates that two protons are liberated per product molecule, and thus highly acidic conditions are finally produced during the conversion. Evident was presented that mechanism 1 is operative in the a-methoxylation reaction and mechanism 2 (Scheme 6) was ruled out on the basis of a base criterion [170]. 

In contrast, anodic cyanation of diphenylacetylene occurs exclusively at the aromatic ring and the triple bond remains intact 4-cyanodiphenylacetylenc is formed in 60% yield. The reaction was run at 2 V (vs. S.C.E.) for 3-9 F mol" using a platinum anode in methanol containing sodium cyanide. Anodic cyanation results in preferred attack at the aromatic nucleus in other systems toluene, mesitylene and hexamethylbenzene give nuclear substitution and little side-chain cyanation under similar conditions in contrast with the corresponding acetoxylation or methoxylation reactions. 

We are reminded of the fascinating role of catalytic selectivity in human behavior by J. R. Smythies discussion of the possible generation of schizophrenia as a result of a slight aberration in catalytic selectivity in a methoxylation reaction, as illustrated by the creation of a molecule manyfold more hallucinogenic than mescaline when methoxylation occurs in the para- as compared to the meta-position of amphetamines. 

The electrochemical reaction-chemical reaction-electrochemical reaction-chemical reaction (ECEC) mechanism is well established for anodic methoxylation reactions of amines, amides, and carbamates. It was confirmed that the anodic methoxylation of fluoroal-Iq l sulfides also proceeds with by way of a typical ECEC mechanism as shown in Scheme 32. ... 

An alternate synthesis of enantiopure (—)-diversonol was recently reported by Tietze et al. using an enantioselective transition-metal-catalyzed domino process (Scheme 14.48). Key step in the synthesis is the formation of a chromane with concomitant introduction of the quaternary stereocenter at C-4a with 96% ee using a domino Wacker/carbonylation/methoxylation reaction in the presence of (S,S)-Bn-BOXAX (310) as ligand [73]. In this reaction phenol 308, containing an alkene moiety, was treated with catalytic amounts of Pd(tfa)2 and 310 in MeOH in the presence of CO and p-benzoquinone the latter is necessary to reoxidize Pd to Pd". One can assume that the first step is an enantiofacial coordination of the Pd" species, which is attacked by the phenolic hydroxyl group to give intermediate... 

BASF in Germany operated a number of commercial, electrolytic processes [44, 56, 57] using a strategy based on the availability of a reliable and simple cell design and then noting the chemistry that can be carried out within this cell. In this cell, a series of horizontal carbon disks (diameter 1 m) were stacked with a separation of 1 mm (maintained by polymer spacers) and the electrolyte was pumped outward from the center of the disks. The cell is operated undivided and as a bipolar stack with bypass currents minimized because the stack is not immersed in electrolyte. The cell is well suited to methoxylation reactions carried out in methanol as the solvent. For example, BASF have carried out the following conversions ... 

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... 

Methoxylation Reaction with methanol to convert Si-OH groups to Si-OCHs groups... 

Synthesis, Scheme 3 Methoxylation reaction of technically relevant benzylic substrate... 

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... 

Not much is known about the last of our inorganic ion reactions, that of cyanide ion. A number of anodic cyanations and cyanation-methoxylation reactions are in the literature. These, anodic oxidations in solutions (methanol usually) of cyanide ion, are reactions of cyanide with cation radicals. Yet, the only successful "chemical reactions, we are aware of are with 10 " which gave small yields of 1- and 3-perylene nitrile (13), and with zinc octaethylporphyrin cation radical, which gives 68% of meso-cyanooctaethylporphyrln (49). 

Given the potential advantages to performing reactions under continuous flow, a variety of chemistries have been modified for flow conditions. A recent example of this was reported by Ley and combined flow and electrochemistry for the methoxylation of cyclic amines (Scheme 1.17) [89]. The chemistry was carried out in a microfluidic electrolytic cell using a substoichiometric amount of [Et N][BF ] as an electrolyte. The authors used a steel cathode and screened a range of materials for the anode and determined that carbon was the most effective for the methoxylation reaction. The chemistry was selective for the a-position, and a range of cyclic amines were successfully functionalized using this approach. 

SCHEME 1.17 Methoxylation reactions using flow electrochemistry [89]. 

---