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Alkyl Methyl Carbonates as Methylating Agents. The O -Methylation of Phenols
Abstract
The O-methylation reaction of a variety of phenols (ArOH: Ar = Ph, p- CH3C6H4, p-ClC6H4, o- and p-CH3COC6H4, and 2-naphthyl) can be conducted in a highly selective manner by using asymmetric alkyl methyl carbonates CH3 OCOOR (R = n-Pr, 3b; n-Bu, 3d; CH3O(CH2)2O(CH2)2, 3e) as alkylating agents. For example, at 150 °C, phenol can be quantitatively converted into anisole in 4.5 h, using 2-(2-methoxyethoxy)ethyl methyl carbonate 3e in the presence of K2CO3 as a catalyst. Compared to the methylation reactions using dimethyl carbonate which require sealed pressurized reaction vessels, asymmetric alkyl methyl carbonates allow much simpler and safer alkylations at ambient pressure. The selectivity towards O- methylation is scarcely affected by the temperature (in the range of 120-150 °C), while it depends on the nature and on the amount of the solvent. DMF and triglyme (triethylene glycol dimethyl ether) have proven to be the better reaction media.
... The polarity of solvent was significantly affecting on selectivity of methylation where dimethylformamide (DMF) and triglyme showed higher rate of methylation. [122] The 1,8-Diazabicyclo [5.4.0]undec-7-ene DBU and microwave accelerated green chemistry in methylation of phenols with dimethyl carbonate as methylating agent and DMF as solvent was studied by Shieh et al. [123] and reported 80-fold enhancement in the rate of reaction. ...
The alkylation process involves two competitive paths of O- and C-alkylation and achieving better selectivity for desired products is a very challenging problem. The development of new process for synthesis of O-methylated products of phenol and dihydric phenols is a subject of high industrial and academic interest. Alkyl phenyl ethers, especially anisole and 4-methoxyphenol, have captivated significant interest due to their increasing applications in pharmaceutical industries. The main emphasis of the present review is to explore the recent development in two catalytic O-alkylation processes. The first process is O-methylation of phenol into anisole and another is selective mono O-methylation of hydroquinone into 4-methoxyphenol. The present article covers O-alkylation methods with methanol and dimethyl carbonate as alkylating agent over various acidic and basic catalytic systems. The catalyst systems analyzed involves Bronsted and Lewis acidic and basic ionic liquids, conventional acids, metal oxides, solid acid and basic catalysts, hydrotalcites, various zeolites and heteropolyacids. The mechanistic behavior of alkylation reactions in presence of different catalytic system is reviewed critically which is important to design new and/or modified catalyst in order to maximize the yield of desired product. Additionally, an influence of reaction parameters, role of catalyst and their active sites on product distribution is described. The review paper gives useful insight for researchers in the field of catalysis and reaction engineering of alkylation reactions. Understandings of the reaction pathways will help in developing reliable kinetic models necessary for process scale-up to industrial scale reactor system.
An environmentally more convenient reaction for the production of industrially important aryl ethyl ethers (ArOEts) is described. ArOEts were selectively obtained in essentially quantitative yields by the reaction of corresponding (hetero)aromatic alcohols (ArOHs) with diethyl carbonate as the environmentally friendly alkylating reagent in the presence of N,N-dimethylacetamide used as polar aprotic cosolvent, and sodium ethoxide as the base. The reactions were carried out in the air under atmospheric pressure at 137°C. Reaction equilibrium was shifted by distilling the ethanol from the reaction mixture. All ArOEts were isolated by evaporation of the reaction mixture, and subsequent extraction with water and diethoxymethane. The ethylation agent and used solvents were non-toxic, recyclable and biologically degradable. Wastewater from the extraction was successfully treated by Fenton oxidation and returned to the next work-up process.
Anilines (R′C6H4NH2: R′ = H, p-MeO, p-Me; p-Cl, and p-NO2) react with a mixture of ethylene carbonate and methanol at 180 °C in the presence of alkali metal exchanged faujasites—preferably of the X-type—to give the corresponding N,N-dimethyl derivatives (R′C6H4NMe2) in isolated yields up to 98%. Evidence proves that methanol is not the methylating agent. The reaction instead takes place through two sequential transformations, both catalyzed by faujasites: first transesterification of ethylene carbonate with MeOH to yield dimethyl carbonate, followed by the selective N-methylation of anilines by dimethyl carbonate. Propylene carbonate, is less reactive than ethylene carbonate, but it can be used under the same conditions. The overall process is highly chemoselective since the competitive reactions between the anilines and the cyclic carbonates is efficiently ruled out. Ethanol and propanol form the corresponding diethyl- and dipropyl- carbonates in the first step, but these compounds are not successful for the domino alkylation of anilines.
The methylating efficiency of dimethyl carbonate (DMC), dimethyl sulfate (DMS), methyl iodide (MeI), and methanol (MeOH) was assessed based on atom economy and mass index. These parameters were calculated for three model reactions: the O-methylation of phenol, the mono-C-methylation of phenylacetonitrile, and the mono-N-methylation of aniline. The analysis was carried out over a total of 33 different procedures selected from the literature. Methanol and, in particular, DMC yielded very favourable mass indexes (in the range 3–6) indicating a significant decrease of the overall flow of materials (reagents, catalysts, solvents, etc.), thereby providing safer greener catalytic reactions with no waste.
Dimethylcarbonate (DMC) is an environmentally friendly substitute for dimethylsulfate (DMS) and methyl halides in methylation reactions. It is also a very selective reagent. The reactions of DMC with methylene-active compounds produce monomethylated derivatives with a selectivity not previously observed. The batchwise monomethylation of arylacetonitriles, arylacetoesters, aroxyacetonitriles, methyl aroxyacetates, benzylarylsulfones and alkylarylsulfones with DMC achieve >99% selectivity at 180-220°C in the presence of K2CO3. Mono-N-methylation of primary aromatic amines at 120-150 °C in the presence of Y- and X-type zeolites, achieved selectivities up to 97%. At high temperature (200°C) and in the presence of potassium carbonate as the catalyst, DMC splits benzylic and aliphatic ketones into two methyl esters; in contrast, DMC converts ketone oximes bearing a methylene group to 3-methyl-4,5-disubstituted-4-oxazolin-2-ones. Dibenzylcarbonate (DBzIC) exhibits similar reactivity, selectively monobenzylating methylene-active compounds.
Arylenediamines are mono-N-alkylated by dialkyl carbonates in the presence of NaY zeolite catalyst in a regioselective and nontoxic process. A recent analysis of the reaction classes used in the syn-thesis of a range of drug candidate development samples has shown that the most common is heteroatom alkyl-ation (19% of the total), with alkylation of nitrogen comprising more than half of these. 1 Additionally, the increasing problems resulting from the toxicity of com-mon alkylating agents are highlighted, which leads the authors to sound a call for an improved alkylation methodology. A further well known and common diffi-culty in synthesis is the prevention of over-alkylation during the conversion of primary to secondary amines. In a recent report Hudson and co-workers address this problem by using alkylnitriles as the N-alkylating agents for anilines under particularly mild conditions. 2 An ear-lier work by Selva and co-workers also goes part way to addressing these concerns. 3 They have demonstrated that dialkyl carbonates efficiently mono-N-alkylate anilines on heating in the presence of the zeolite NaY (sodium-exchanged faujasite). Both the zeolite and the carbonate esters are readily available and cheap, 4 and may be recovered and recycled. The carbonate esters are much less toxic than traditional alkylating agents such as alkyl halides, sulfates or sulfonates. The by-products of reaction, the alcohol itself and carbon dioxide, are also relatively innocuous. Selva established selectivity for primary over secondary in amine alkyl-ation and for N-over O-alkylation in the reaction of aminophenols and aminobenzoic acids. 3c We now describe an additional useful and more surpris-ing dimension to the selectivity displayed by this reagent combination in the alkylation of arylenediamines. When we initially exposed a phenylenediamine to the NaY-catalysed dialkyl carbonate alkylation reaction condi-tions, we had expected to observe N,N 0 -dialkylation. In fact these conditions lead to highly selective—some-times specific—mono-N-alkylation of just one of the amino groups present (Scheme 1).
" Chemical equation presented" Simple methodology: A layered double hydroxide-supported L-methionine (LDH-Met) catalyst is designed in a simple methodology to explore its synthetic utility in biologically relevant reactions. The organocatalyst is characterized by FT-IR, TGA/DTA, powder XRD, and EDX spectroscopic techniques. This material has been successfully utilized for the preparation of aryl methyl ethers and esters from the corresponding phenols and carboxylic acids, respectively, in moderate to high yields (see scheme).
The industrially important alkyl aryl ethers, of which anisole is the simplest form, can be synthesized by reacting the corresponding phenols with the environmentally benign dimethyl carbonate (DMC). The reaction is carried out under mild conditions of temperature and pressure. Excellent yields and selectivity of product were obtained after a few hours of reaction.
Zugl.: Oldenburg, Univ., Diss., 2001. Computerdatei im Fernzugriff.
At atmospheric pressure and at 130-160 degrees C, primary aromatic amines (p-XC6H4NH2, X = H, Cl, NO2) are mono-N-alkylated in a single step, with symmetrical and asymmetrical dialkyl carbonates [ROCOOR', R = Me, R' = MeO(CH2)2O(CH2)2; R = R' = Et; R = R' = benzyl; R = R' = allyl; R = Et, R' = MeO(CH2)2O(CH2)2], in the presence of a commercially available NaY faujasite. No solvents are required. Mono-N-alkyl anilines are obtained with a very high selectivity (90-97%), in good to excellent yields (68-94%), on a preparative scale. In the presence of triglyme as a solvent, the mono-N-alkyl selectivity is independent of concentration and polarity factors. The reaction probably takes place within the polar zeolite cavities, and through the combined effect of the dual acid-base properties of the catalyst.
1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) is a novel and active catalyst in promoting the methylation reaction of phenols, indoles, and benzimidazoles with dimethyl carbonate under mild conditions. Additional rate enhancement is accomplished by applying microwave irradiation. By incorporating tetrabutylammonium iodide, the same microwave reactions can be further accelerated. By combining these acceleration strategies, very slow chemical transformations that take up to several days can be performed efficiently in high yield within minutes. [reaction: see text]
1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) is an effective nucleophilic catalyst for carboxylic acid esterification with dimethyl carbonate (DMC). The reaction pathway of this new class of nucleophilic catalysis has been studied. A plausible, multistep mechanism is proposed, which involves an initial N-acylation of DBU with DMC to form a carbamate intermediate. Subsequent O-alkylation of the carboxylate with this intermediate generates the corresponding methyl ester in excellent yield. In the absence of DBU or in the presence of other bases, such as ammonium hydroxide or N-methylmorpholine, the same reaction affords no desired product. This method is particularly valuable for the synthesis of methyl esters that contain acid-sensitive functionality.
Dimethylcarbonate (DMC) is a valuable methylating reagent that can replace methyl halides and dimethylsulfate in the methylation of a variety of nucleophiles. It couples tunable reactivity and unprecedented selectivity towards mono-C- and mono-N-methylation. In addition, it is a prototype example of a green reagent, because it is nontoxic, is made by a clean process, is biodegradable, and reacts in the presence of a catalytic amount of base, thereby avoiding the formation of undesirable inorganic salts as by-products. Depending on the reaction conditions, DMC can be reacted under plug-flow, CSTR, or batch conditions. Other remarkable reactions are those where DMC behaves as an oxidant. The reactivity of other carbonates is reported as well.
Dimethyl carbonate (DMC) is a versatile compound that represents an attractive eco-friendly alternative to both methyl halides (or dimethyl sulfate) and phosgene for methylation and carbonylation processes, respectively. In fact, the reactivity of DMC is tunable: at T = 90 degrees C, methoxycarbonylations take place, whereas at higher reaction temperatures, methylation reactions are observed with a variety of nucleophiles. In the particular case of substrates susceptible to multiple alkylations (e.g., CH(2)-active compounds and primary amines), DMC allows unprecedented selectivity toward mono-C- and mono-N-methylation reactions. Nowadays produced by a clean process, DMC possesses properties of nontoxicity and biodegradability which makes it a true green reagent to use in syntheses that prevent pollution at the source. Moreover, DMC-mediated methylations are catalytic reactions that use safe solids (alkaline carbonates or zeolites), thereby avoiding the formation of undesirable inorganic salts as byproducts. The reactivity of other carbonates is reported as well: higher homologues of DMC (i.e., diethyl and dibenzyl carbonate), are excellent mono-C- and mono-N-alkylating agents, whereas asymmetrical methyl alkyl carbonates (ROCO(2)Me with R > or = C(3)) undergo methylation processes with a chemoselectivity up to 99%.
[reaction: see text] In the presence of NaY faujasite as the catalyst, the reaction of bifunctional anilines (1-4: XC6H4NH2; X = OH, CO2H, CH2OH, and CONH2) with methyl alkyl carbonates [MeOCO2R': R' = Me or MeO(CH2)2O(CH2)2] proceeds with a very high mono-N-methyl selectivity (XC6H4NHMe up to 99%), and chemoselectivity as well, with other nucleophilic functions (OH, CO2H, CH2OH, CONH2) fully preserved from alkylation and/or transesterification reactions. Aromatic substituents, however, modify the relative reactivity of amines 1-4: good evidence suggests that, not only steric and electronic effects, but, importantly, direct acid-base interactions between substituents and the catalyst are involved. Weakly acidic groups (OH, CH2OH, CONH2, pKa > or = 10) may help the reaction, while aminobenzoic acids (pKa of 4-5) are the least reactive substrates. The solvent polarity also affects the reaction, which is faster in xylene than in the more polar diglyme. The mono-N-methyl selectivity is explained by the adsorption pattern of reagents within the zeolite pores: a B(Al)2 displacement of the amine on methyl alkyl carbonate should occur aided by the geometric features of the NaY supercavities. Different factors account for the reaction chemoselectivity. Evidence proves that the polarizability of the two nucleophilic terms (NH2 and X groups) of anilines is relevant, although adsorption and confinement phenomena of reagents promoted by the zeolite should also be considered.
The industrially important alkyl aryl ethers (ArOR) were selectively obtained in good yields from the O-alkylation of the corresponding phenols with the environmentally benign reagents, dimethyl carbonate or diethyl carbonate. The reactions were carried out under atmospheric pressure, in a homogenous process, without solvent and in the presence of potassium carbonate as catalyst.
Synthetically established methods for methylation of phenols and demethylation of methyl phenyl ethers rely in general on hazardous reagents or/and harsh reaction conditions and are irreversible. Consequently, alternative regioselective methods for the reversible formation and breakage of C-O-ether bonds to be performed under mild and sustainable conditions are highly desired. Here we present a biocatalytic shuttle concept making use of corrinoid-dependent methyl transferases from anaerobic bacteria. The two-component enzymatic system consists of a corrinoid protein carrying the cofactor and acting as methyl group shuttle, and a methyltransferase catalyzing both methylation and demethylation in a reversible fashion. Various phenyl methyl ethers are successfully demethylated and serve in addition as sustainable methylating agents for the functionalization of various substituted catechols. Therefore, this methyl transfer approach represents a promising alternative to common chemical protocols and a valuable add-on for the toolbox of available biocatalysts.
At 250-300 °C and 30-50 bar, a continuous-flow (CF) transesterification of different dialkyl and alkylene carbonates (dimethyl-, diethyl-, dibenzyl-, and propylene carbonate, respectively) with two glycerol derived acetals (glycerol formal and solketal) was investigated without any catalyst. An unprecedented result was obtained: not only the desired process occurred, but also the formation of the corresponding mono-transesterification products took place with an excellent selectivity (up to 98%) in all cases. Under isothermal conditions, a study on the effect of pressure allowed to optimize the conversion of acetals (up to 95%) for the reactions of dimethyl- and diethyl- carbonate (DMC and DEC, respectively). This proved that an abrupt progress of the reaction occurred for very small increments of pressure. For example, at 250 °C, the thermal transesterification of DMC with glycerol formal showed a sharp increase of the conversion from 1-2% at 30 bar to ~85% at 37 bar, respectively. The lower the temperature, the lower the pressure interval at which the onset of the reaction was achieved. The absence of catalysts allowed to run CF-reactions virtually indefinitely and with a very high productivity (up to 68 mg/min) compared to the capacity (1 mL) of the used CF-reactor. Products of the transesterification of DMC and DEC were isolated in good-to-almost quantitative yields. In the case of heavier carbonates, steric reasons were responsible for the considerably lower reactivity of propylene carbonate (PC) with respect to DMC and DEC; while, the transesterification of dibenzyl carbonate (DBnC, solid at room temperature) with glycerol formal required the presence of acetone as an additional solvent/carrier. Although the reactions of both PC and DBnC were not optimized, results offered a proof-of-concept on the extension of thermal transesterification processes to higher homologues of linear and alkylene carbonates.
The worldwide urge to embrace a sustainable and bio-compatible chemistry has led industry and academia to the development of chlorine-free methodologies focused on the use of CO2 and CO2-based compounds...
An archetype of a green and sustainable strategy for the catalytic upgrading of both anilines and bio-based derivatives including glycerol acetals, p-coumaryl-like alcohols, and lactones can be devised by the use of dimethyl carbonate (DMC). In the presence of different heterogeneous catalysts such as alkaline carbonates and alkali metal-exchanged faujasites, DMC allows quantitative mono-N-methylation and O-methylation processes with excellent selectivity up to 99% and no by-products except for methanol (recyclable to the synthesis of DMC) and CO2. Also, selective transesterifications of DMC with glycerol acetals and lactones can be achieved under thermal or catalytic conditions. The mechanism of such reactions has been formulated based on the steric requisites and the amphoteric nature of faujasites, the combined effect of the temperature and base catalysts, and the ambident electrophilic reactivity of DMC. Overall, methylations and methoxycarbonylations mediated by DMC are not only more selective but far safer than conventional procedures involving noxious phosgene and methyl halides or dimethyl sulfate.
Sulfur and nitrogen (half-)mustard carbonate analogues are a new class of compounds, easily synthesized by methoxycarbonylation reaction of the parent alcohols with dialkyl carbonates. In this work, their reactivity as novel, green electrophiles is reported. Reactions have been conducted in autoclave conditions at high temperature (180°C), under pressure and in absence of any base, as well as, in neat at atmospheric pressure, lower temperature (150°C) and in the presence of a catalytic amount of a base. Several nucleophiles have been investigated resulting, in some cases, in unexpected compounds, i.e., six-membered heterocycle piperidine. Reaction mechanism and kinetics have been studied confirming that these compounds retain the anchimeric effect of their mustard gas analogues, without being toxic. Noteworthy, a symmetrical nitrogen mustard carbonate has also been employed as reagent in the preparation of a new family of macrocycles i.e., azacrowns, before not easily accessible.
The Omethylation reaction of different phenols with dimethyl carbonate (DMC) using ionic liquid as catalysts was investigated. The results showed that catalytic performance of [Bmim]Cl was good, and the yield of O-methylation reached 90% and no by-product from G-methylation was observed under the reaction conditions of the molar ratio of the phenol and DMC to ionic liquid 1:2:0.5, 150°C and reaction time 5 h. Moreover the structure of [Bmim]Cl was unchanged after reaction.
An environmentally friendly method was established for the N‐methylation of the 5‐substituted 1H‐tetrazoles with a green reagent: DMC. DABCO was the optimal catalyst, and hazardous chemicals were avoided in this protocol. A plausible catalytic mechanism is proposed, which consists of a DABCO‐activated process and a thermally induced rearrangement of tetrazole carbamates.
Sulfur iprit carbonate analogues have been investigated in neat conditions at atmospheric pressure, in the presence and in the absence of a catalytic amount of base. Furthermore, their reaction mechanism has been discussed in detail. In these novel reaction conditions, sulfur mustard carbonate analogues, that previously showed poor or no reactivity, remarkably undergo efficient nucleophilic substitution with several substrates.
A selective alkylation of carboxylic acids and phenols was optimized with 1,2-dimethylimidazole (DMI) using dimethyl carbonate (DMC) and diethyl carbonate (DEC). The reaction mechanism was determined by the formation of the diethoxy(1,2-dimethyl-1H-imidazolidium-1-yl)methoxy (DEIM) intermediate. The dependence of the amount of DMI on the rate of the ethylation reaction was established, concluding that DMI is a novel and active nucleophilic catalyst. The rate of ethyl benzoate formation is shown. The reactions with DEC require more drastic conditions, while those with DMC are achieved with better efficiency under mild conditions. Solvent free microwave reactions with DMI and DMC or DEC proceed at high temperatures. In the absence of DMI these reactions do not proceed.
At 130-150°C and in the presence of catalytic K2CO 3, o-aminophenol (1) readily reacts with dialkyl carbonates (2: ROCO2R; 2a: R = Me, 2b: Et, 2c: Allyl, 2d: Bn) to give the corresponding N-alkylbenzoxazol-2-ones (3a-d) in high yields (88-98%). This reaction is a rare example where dialkyl carbonates may simultaneously act as carbonylating and alkylating agents likely through a BAc2/B A12 sequence. Moreover, compounds 2a-c serve also as solvents. In the case of 2d, 1,2-dimethoxyethane (DME) is the reaction medium.
Electrochemical carboxylation of benzylic carbonates was successfully performed as an alternative method for the synthesis of phenylacetic acids by using a one-compartment cell equipped with a Pt plate cathode and an Mg rod anode in CH3CN to afford the corresponding phenylacetic acids in good yields.
Die Reaktivdestillation (RD) wird gegenwärtig vor allem zur Umsatzsteigerung in gleichgewichtslimitierten Reaktionssystemen verwendet, die häufig nur eine Hauptreaktion aufweisen. Diese Arbeit hingegen beschäftigt sich mit dem Einsatz der RD in chemischen Systemen mit mehr als einer Hauptreaktion. In solchen Multi-Reaktionssystemen ist nicht nur der Umsatz der Edukte, sondern auch die Selektivität des Zielprodukts durch das chemische Gleichgewicht begrenzt. Ungeachtet, ob das Zielprodukt als Zwischenprodukt oder nach mehreren aufeinanderfolgenden Reaktionen gebildet wird, kann die RD zur Überwindung solcher Selektivitätslimitierungen beitragen. Dieses Potenzial wird am Beispiel der konsekutiven Umesterung von Dimethylcarbonat mit Ethanol untersucht. Die Ergebnisse umfassender experimenteller Studien in einer Technikumskolonne werden präsentiert, um den Einfluss entscheidender Betriebsparameter auf das Prozessverhalten zu untersuchen. Reactive distillation (RD) is currently used to increase the reactant conversion in chemical equilibrium limited reaction systems that usually consist of a single main reaction. This work focuses on the application of RD to chemical systems that consist of more than a single main reaction. In such multiple reaction systems, not only the reactant conversion but also the selectivity of the target product is limited by chemical equilibrium. In this case, reactive distillation would allow overcoming such selectivity limitations, regardless of whether the target product is formed as an intermediate product or at the end of several consecutive reactions. Both cases are investigated on the example of the consecutive transesterification of dimethyl carbonate with ethanol. Comprehensive pilot-scale experiments were performed to study the effect of decisive operating parameters on the RD column's behavior.
We have found that the use of a conventional, heated, standard 316 stainless steel or steel-braided PTFE tube reactor is a good and easily scalable alternative to the use of continuous microwave-heated reactors. The heat-up is almost as fast as with microwave heating, and the reactors can easily be scaled towards large-scale production. The transfer of the reported microwave procedure to the continuous flow method went very smoothly, and we found that we could further optimize the reaction to a catalytic procedure where only 10 mol % of DBU is needed with only 3 equiv of DMC. The reaction can be run neat in cases where the starting material is soluble in DMC as phenol is, or with a small amount of DMF (2–3 vol). The reaction is efficient for different types of phenols, giving a clean reaction in high yields.
Reactive distillation (RD) is currently used to increase reactant conversion and the purity of the target product. Our work focuses on the application of RD to reaction systems that feature more than one target product. In such systems, an RD column acts as a multipurpose reactor to produce several target products with high selectivities by changing the operating conditions. A promising example of such a multiple-product system is the consecutive transesterification of dimethyl carbonate with ethanol to form the target products ethyl methyl carbonate and diethyl carbonate. This article presents for the first time a comprehensive experimental study on that reaction system in a pilot-sale RD column. Data reconciliation tests confirm the reliability of the experimental results. The effect of decisive operating parameters on the RD column's behavior was extensively studied, and the potential of an RD column to act as a multipurpose reactor was experimentally verified.
Glycerol offers an easy and green route for the synthesis of aryloxypropanediols of known pharmacological activity. Glycerol is selectively converted to aryloxypropanediols in a one-pot reaction, through in situ formed glycerol carbonate, under benign and solvent-free conditions. Catalyst and unreacted reagent can be recycled.
The C,N-chelated tri-, di- and monoorganotin(IV) halides react with equimolar amounts of CF3COOAg to give corresponding C,N-chelated organotin(IV) trifluoroacetates. The set of prepared tri-, di- and monoorganotin(IV) trifluoroacetates bearing the LCN ligand (where LCN is 2-(N,N-dimethylaminomethyl)phenyl-) was structurally characterized by X-ray diffraction analyses, multinuclear NMR and IR spectroscopy. In the case of triorganotin(IV) trifluoroacetates and (LCN)2Sn(OC(O)CF3)2, no tendency to form hydrolytic products, or instability towards the moisture was observed. LCNRSn(OC(O)CF3)2 (where R is n-Bu or Ph) and LCNSn(OC(O)CF3)3 forms upon crystallization from THF in the air mainly dinuclear complexes in which the two tin atoms are interconnected either by hydroxo-bridges or by an oxo-bridge and/or by a bridging trifluoroacetate(s). In the case of hydrolysis of LCN(n-Bu)Sn(OC(O)CF3)2, a zwitterionic stannate of formula LCN(n-Bu)Sn(OC(O)CF3)2·CF3COOH was isolated from the mother liquor, too. Products of hydrolysis of LCN(n-Bu)Sn(OC(O)CF3)2 and LCNSn(OC(O)CF3)3, and some other oxygen bridged organotin(IV) compounds containing the same ligand, were tested as possible catalysts of some transesterification reactions as well as in direct dimethyl carbonate (DMC) synthesis from CO2 and methanol.
The O-methylation of phenols, including the sterically hindered phenols, with dimethyl carbonate (DMC) under mild conditions of temperature and pressure was described. The reaction was carried out in the presence of tetrabutylammonium bromide (TBAB), in a semi-continuous process. Aryl methyl ethers were rapidly and selectively obtained in good yields.
Selective C-methylation of phenol to o-cresol and 2,6-xylenol in high yields has been carried out with methanol over borate zirconia solid acid catalyst. The maximum conversion of 70 and 65% selectivity for corresponding ortho-alkylated products (o-cresol and 2,6-xylenol) was obtained with 1–2% anisole as O-alkylated product. A series of borate zirconia catalysts with 5–30mol% B2O3 loading were prepared and calcined at different temperatures. The XRD results reveal the formation of single phase cubic zirconia after addition of B2O3. The cubic structure was stable up to 650°C, above which it transformed to monoclinic structure. Borate zirconia containing 5mol% B2O3 calcined at 650°C was found to be the most active catalyst among the series indicating the influence of composition and structure on the conversion and selectivity. The FTIR results provided the evidence for the vertical orientation of phenol aromatic ring on the catalyst surface, which explains the selective C-alkylation of phenol. The influence of various experimental parameters on phenol conversion and product selectivity has been investigated. The catalyst was active for 150h time on stream without any deactivation showing its longer life. The catalytic activity and selectivity is correlated with its acidity and structure.
In the presence of onium salts, at 140-170 degrees C, methyl alkyl carbonates [1a-c, ROCO2Me, R = MeO(CH2)2[O(CH2)2]n; n = 2-0, respectively] react with primary aromatic amines (XC6H4NH2, X= p-OMe, p-Me, H, p-Cl, p-CO2Me, o-Et, and 2,3-Me2C6H3NH2) to yield the corresponding N,N-dimethyl derivatives (ArNMe2) with high selectivity (up to 96%) and good isolated yields (78-95%). Phosphonium salts (e.g., Ph3PEtI and n-Bu4PBr) are particularly efficient catalysts. Overall, a solvent-free reaction is coupled with safe methylating agents (1a-c) made from nontoxic dimethyl carbonate.
Mono-C-methylation of arylacetonitriles and methyl arylacetates by dimethyl carbonate: A general method for the synthesis of pure 2-arylpropionic acids. 2-phenylpropionic acid
Reaction of phenols in dimethyl carbonate in the presence of cesium carbonate at 120-160° C gave aryl methyl ethers in good yields, whereas the reaction of aliphatic alcohols gave the corresponding alkyl carbonates. This method provides a useful synthetic method for preparation of various aryl methyl ethers without using toxic methyl iodide or dimethyl sulfate. O-Methylation of the aromatic hydroxy group of estradiol was carried out in 2 steps without protection of the alcoholic hydroxy group in the same molecule.
A stereoelectronic effect in bimolecular nucleophilic substitution at a benzylic center has been observed in the rates of reaction of thiourea in dimethyl-d6 sulfoxide with a series of sulfonium perchlorates with differing degrees of constraint in the orientation of the reacting C-S+ bond with respect to the plane of the aromatic ring. The substrates and their relative rates (at 37°C, unless otherwise noted) are as follows: (a, highly constrained) 2-ethyl-1,3-dihydrobenzo[c]thiophenium perchlorate (4b), 1.00, and 2-isobutyl-1,3-dihydrobenzo[c]thiophenium perchlorate (4c), 2.8; (b, partly constrained) 2-ethyl-3,4-dihydro-1H-2-benzothiopyranium perchlorate (7), 45 (at 82°C); (c, unconstrained) S,S-dibenzyl-S-ethylsulfonium perchlorate (5b), 8.1 × 103. An (8 × 103)-fold rate difference was also observed between S,S-dibenzyl-S-ethylsulfonium tetrafluoroborate (5a) and 2-ethyl-1,3-dihydrobenzo[c]thiophenium tetrafluoroborate (4a) with potassium thiocyanate-18-crown-6 in acetonitrile-d3. Analysis of these rate differences, taken with inspection of molecular models which show that the observed rate differences are not adequately accounted for by simple nonbonding or angle strain effects, clearly indicates a dihedral angle dependent factor consistent with π-overlap between p-orbitals on the aromatic ring and the carbon atom undergoing substitution. The "orbital-overlap factor" is estimated to increase the reactivity of the benzylic center in 5b (4 × 103)-fold relative to that of the corresponding ethyl group (in 21). A single-crystal X-ray analysis on 4c showed the salt crystallizes in space group P21/n, unit cell dimensions a = 17.382 (1) Å, b = 9.1731 (6) Å, c = 8.7828 (3) Å, and β = 91.7 (2)°, with Z = 4. On the basis of 2054 unique data with F2 > 2σ, full matrix refinement converged at R = 0.044 for 232 variables. There is a dihedral angle of 3.8° between the C2,S,C9 plane and the plane of the aromatic ring consistent with the observed low reactivity of the benzylic center and the present analysis. The entropies of activation for benzylic substitution of the cyclic and acyclic substrates (4b, 4c, and 5b) with thiourea in Me2SO-d6 are very similar (-12 ± 1 cal mol-1 K-1), in contrast to the great ΔS† difference reported for an analogous α-carbonyl system by Bartlett and Trachtenberg; the origin of this difference is discussed.
Poly(ethylene glycol)-400 (PEG-400) was used to catalyze the allylation of phenoxide with allyl bromide in the two-phase reaction system. n-Decane was employed as the aprotic organic solvent phase, and a mixture of H2O and PEG-400 was used as the protic solvent phase. The initial O-allylation rate increased dramatically with the increase of PEG-400 content in the protic solvent phase. The reaction rate in n-decane/PEG-400 was about 60 times the reaction rate in n-decane/H2O. The extraction constant of allyl bromide and the reaction rate constant for the allylation of phenoxide in a H2O-PEG-400 homogeneous phase were determined to assist in identifying the mechanism of the two-phase reaction. It was found that the reaction occurred both in the aprotic organic solvent phase and in the protic solvent phase when the amount of PEG-400 in the protic solvent phase was less than 60%. However, the reaction only took place in the H2O-PEG-400 phase when the amount of PEG-400 in the protic solvent phase was greater than 60%.