Reaction Pathways in Carbonates and Esters.

This review reports on the competition/collaboration among intertwined base-catalyzed acyl cleavage bimolecular mechanism (BAc 2)/base-catalyzed alkyl cleavage bimolecular mechanism (BAl 2) or the related acid catalyzed mechanisms AAc 2/AAl 2 and AAl 1 concerning Carbonates chemistry also in comparison with Esters reactivity. A consistent analysis of the experimental data so far available in the literature led to proposing a theoretical Model outlining the differences in energy profiles among the above-mentioned reaction mechanisms. The reactions involving Carbonates are so tightly interconnected that the formation of the final product is driven by a precise not interfering sequence of BAc 2-BAl 2 (or AAl 2-AAc 2) mechanisms. When entropic effect (in cyclisations) or an anchimeric effect (mustard carbonates, isosorbide methylation) are involved, the difference in Gibbs activation energy is reduced allowing chemical transformations that would normally require higher temperatures. In these cases (intramolecular alkylation, cyclisation reaction, and alkylation by mustard carbonates) only a catalytic amount of base is required as the leaving group CH3 OCOO- decomposes restoring the base. As Green Chemistry is concerned, syntheses with much lower environmental impact are achieved with Carbonates when compared with the corresponding ones involving Chlorine chemistry.

Dialkyl Carbonates in the Green Synthesis of Heterocycles.

This review focuses on the use of dialkyl carbonates (DACs) as green reagents and solvents for the synthesis of several 5- and 6-membered heterocycles including: tetrahydrofuran and furan systems, pyrrolidines, indolines, isoindolines, 1,4-dioxanes, piperidines, and cyclic carbamates. Depending on the heterocycle investigated, the synthetic approach used was different. Tetrahydrofuran systems, pyrrolidines, indolines, isoindoline, and 1,4-dioxanes were synthesized using dimethyl carbonate (DMC) as sacrificial molecule (BAc2/BAl2 mechanism). Cyclic carbamates, namely 1,3-oxazin-2-ones, were prepared employing DACs as carbonylating agents, either by BAc2/BAl2 mechanism or through a double BAc2 mechanism. Piperidines were synthetized taking advantage of the anchimeric effect of a new family of dialkyl carbonates, i.e., mustard carbonates. Finally, in the case 5-hydroxymethylfurfural (HMF), DMC has been employed as efficient extracting solvent of this extensively investigated bio-based platform chemical from the reaction mixture. These synthetic approaches demonstrate, once again, the great versatility of DACs and their-yet to be fully explored-potential as green reagents and solvents in the synthesis of heterocycles.

ß-Aminocarbonates in Regioselective and Ring Expansion Reactions.

The reactivity of ß-aminocarbonates as anisotropic electrophiles has been investigated with several phenols. Products distribution shows that the regioselectivity of the anchimerically driven alkylation reaction depends on the nucleophiles. The results suggest that in the presence of nucleophiles that are also good leaving groups, the reaction takes place under thermodynamic control favoring the attack on the most sterically hindered carbon of the cyclic aziridinium intermediate. Furthermore, when an enantiomerically pure pyrrolidine-based carbonate was used, the reaction with phenols proceeds via a bicyclic aziridinium intermediate leading to the stereoselective synthesis of optically active 3-substituted piperidines via ring expansion reaction. These results were confirmed both by NMR spectroscopy and X-ray diffraction analysis.

Isosorbide and dimethyl carbonate: a green match.

In this review the reactivity of the bio-based platform compounds D-sorbitol and isosorbide with green reagents and solvent dimethyl carbonate (DMC) is reported. Dehydration of D-sorbitol via DMC in the presence of catalytic amounts of base is an efficient and viable process for the preparation of the industrially relevant anhydro sugar isosorbide. This procedure is "chlorine-free", one-pot, environmental friendly and high yielding. The reactivity of isosorbide with DMC is equally interesting as it can lead to the formation of dicarboxymethyl isosorbide, a potential monomer for isosorbide-based polycarbonate, and dimethyl isosorbide, a high boiling green solvent. The peculiar reactivity of isosorbide and the non-toxic properties of DMC represent indeed a green match leading to several industrial appealing potential applications.

Azacrown Ethers from Mustard Carbonate Analogues.

Polycondensation of a nitrogen mustard carbonate analogue with aromatic diols under dilution conditions affords a series of azacrown ethers previously not easily accessible as they require multistep synthesis including protection, purification, cyclization and methylation. This novel synthesis relies upon the anchimeric effect of the nitrogen mustard carbonate and it does not require the use of any base.

Synthesis of five-membered cyclic ethers by reaction of 1,4-diols with dimethyl carbonate.

The reaction of 1,4-diols with dimethyl carbonate in the presence of a base led to selective and high-yielding syntheses of related five-membered cyclic ethers. This synthetic pathway has the potential for a wide range of applications. Distinctive cyclic ethers and industrially relevant compounds were synthesized in quantitative yield. The reaction mechanism for the cyclization was investigated. Notably, the chirality of the starting material was maintained. DFT calculations indicated that the formation of five-membered cyclic ethers was energetically the most favorable pathway. Typically, the selectivity exhibited by these systems could be rationalized on the basis of hard-soft acid-base theory. Such principles were applicable as far as computed energy barriers were concerned, but in practice cyclization reactions were shown to be entropically driven.

Insight into the hard-soft acid-base properties of differently substituted phenylhydrazines in reactions with dimethyl carbonate.

Following the preliminary studies on the reactivity of the ambident nucleophile phenylhydrazine with dimethyl carbonate, investigations involving para-substituted phenylhydrazines were carried out in order to probe differences in the reactivity within this class of nucleophile. Phenylhydrazines substituted by electron withdrawing or donating substituents showed an increase in reactivity of the phenylhydrazine toward dimethyl carbonate. Under the basic conditions used, all phenylhydrazines displayed hard nucleophilicity, signifying that para-substitution on the phenyl ring has little effect on the hard-soft behavior of this class of nucleophile. This conclusion fits well within the results previously obtained using other para-substituted nucleophiles, i.e., phenols.

Reaction of the ambident electrophile dimethyl carbonate with the ambident nucleophile phenylhydrazine.

To explore the ambident electrophilic reactivity of dimethyl carbonate (DMC), reactions with the ambident nucleophile phenylhydrazine were investigated. When a Brönsted base was used, selective carboxymethylation occurred at N-1, after that several other compounds were produced selectively utilizing various conditions. Formation of these compounds was explained by using the Hard-Soft Acid-Base (HSAB) theory. Catalysis by some metal salts altered the reactivity of phenylhydrazine, which effected selective carboxymethylation at N-2 of phenylhydrazine instead.

Multiphasic heterogeneous catalysis mediated by catalyst-philic liquid phases.

This critical review addresses heterogeneous catalysis in systems where multiple liquid phases coexist and where one of the phases is catalyst-philic. This technique provides built-in catalyst separation, and product recovery for organic reactions. Focus is placed on the components of the multiphasic systems with emphasis on the constituents of the catalyst-philic phases (PEGs, onium salts, ionic liquids) that incorporate the catalysts, as well as on the effects on catalytic efficiency. It collects a wide body of scattered information that is often labelled with different terms.

Selective n,n-dimethylation of primary aromatic amines with methyl alkyl carbonates in the presence of phosphonium salts.

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.

Highly chemoselective methylation and esterification reactions with dimethyl carbonate in the presence of NaY faujasite. The case of mercaptophenols, mercaptobenzoic acids, and carboxylic acids bearing OH substituents.

In the presence of NaY faujasite, the reactions of dimethyl carbonate (DMC) with several ambident nucleophiles such as o- and p-mercaptophenols (1a,b), o- and p-mercaptobenzoic acids (2a,b), o- and p-hydroxybenzoic acids (3a,b), mandelic and phenyllactic acids (4, 5), have been explored under batch conditions. Highly chemoselective reactions can be performed: at 150 degrees C, compounds 1 and 2 undergo only a S-methylation reaction, without affecting OH and CO2H groups; at 165 degrees C, acids 3-5 form the corresponding methyl esters, while both their aromatic and aliphatic OH substituents are fully preserved from methylation and/or transesterification processes. Typical selectivities are of 90-98% and isolated yields of products (S-methyl derivatives and methyl esters, respectively) are in the range of 85-96%. A comparative study with K2CO3 as a catalyst is also reported. Although the base (K2CO3) turns out to be more active than the zeolite, the chemoselectivity is elusive: compounds 2a,b undergo simultaneous S-methylation and esterification reactions, and acids 3-5 yield complex mixtures of products of O-methylation, O-methoxycarbonylation, and esterification of their OH and CO2H groups, respectively. Overall, the combined use of a nontoxic reagent/solvent (DMC) and a safe promoter (NaY) imparts a genuine ecofriendly nature to the investigated synthesis.

Triphasic liquid systems: generation and segregation of catalytically active Pd nanoparticles in an ammonium-based catalyst-philic phase.

A triphasic liquid system fabricated from isooctane, aqueous base, and trioctylmethylammonium chloride/decanol promoted the formation of Pd-nanoparticles in the size range of 2-4 nm which remained immobilised in the onium phase, catalysed organic reactions, and could be recycled.

Mono-N-methylation of functionalized anilines with alkyl methyl carbonates over NaY faujasites. 4. Kinetics and selectivity.

[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.

Synthesis of methyl carbamates from primary aliphatic amines and dimethyl carbonate in supercritical CO2: effects of pressure and cosolvents and chemoselectivity.

[reaction: see text] At 130 degrees C, in the presence of CO2 (5-200 bar), primary aliphatic amines react with dimethyl carbonate (MeOCO2Me, DMC) to yield methyl carbamates (RNHCO2Me) and N-methylation side-products (RNHMe and RNMe2). The pressure of CO2 largely influences both the reaction conversion and the selectivity toward urethanes: in general, conversion goes through a maximum (70-80%) in the midrange (40 bar) and drops at lower and higher pressures, whereas selectivity is continuously improved (from 50% up to 90%) by an increase of the pressure. This is explained by the multiple role of CO2 in (i) the acid/base equilibrium with aliphatic amines, (ii) the reactivity/solubility of RNHCO2- nucleophiles with/in DMC, and (iii) the inhibition of competitive N-methylation reaction of the substrates. Cosolvents also affect the reaction: in particular, a drop in selectivity is observed with polar protic media (i.e., MeOH), plausibly because of solvation effects (through H-bonds) of RNHCO2- moieties. The reaction shows also a good chemoselectivity: bifunctional aliphatic amines bearing either aromatic NH2 or OH substituents [XC6H4(CH2)n NH2, X = NH2, OH; n = 1, 2], undergo methoxycarbonylation reactions exclusively at aliphatic amino groups and give the corresponding methyl carbamates [XC6H4(CH2)n NHCO2Me] in 39-65% isolated yields.

Dimethyl carbonate as an ambident electrophile.

[reaction: see text] The features of various anions having different soft/hard character (aliphatic and aromatic amines, alcohoxydes, phenoxides, thiolates) are compared with regard to nucleophilic substitutions on dimethyl carbonate (DMC), using different reaction conditions. Results are well in agreement with the Hard-Soft Acid-Base (HSAB) theory. Accordingly, the high selectivity of monomethylation of CH(2) acidic compounds and primary aromatic amines with DMC can be explained by two different subsequent reactions, which are due to the double electrophilic character of DMC. The first step consists of a hard-hard reaction and selectively produces a soft anion, which, in the second phase, selectively transforms into the final monomethylated product, via a soft-soft nucleophilic displacement (yield >99% at complete conversion, using DMC as solvent).

Heck reaction catalyzed by Pd/C, in a triphasic-organic/Aliquat 336/aqueous-solvent system.

The rate of the Pd/C catalyzed Heck coupling of Ar-I with CH(2)=CH-R is accelerated tenfold by the presence of Aliquat 336 (A336), a well known phase transfer catalyst, and an ionic liquid. Both when conducted in A336 as solvent, and in an isooctane/A336/aqueous triphasic mixture, the Heck reaction of aryl iodides with electron deficient olefins, catalyzed by Pd/C, proceeds with high yields and selectivity. When KOH is used instead of Et(3)N, selective formation of the biphenyl rather than the Heck product, is observed. Aryl bromides react more sluggishly, and only the more activated ones undergo the Heck reaction. In the absence of the olefin, aryl halides possessing an electron withdrawing group are reduced to the corresponding Ar-H.

Selective n,n-dibenzylation of primary aliphatic amines with dibenzyl carbonate in the presence of phosphonium salts.

In the presence of catalytic amounts of tetraalkylphosphonium salts and under solventless conditions, primary aliphatic amines (RNH(2): R = PhCH(2), Ph(CH(2))(2), n-decyl, and 1-naphthylmethyl) are efficiently N-benzylated to the corresponding RN(CH(2)Ph)(2), using dibenzyl carbonate as the benzylating reagent. Compared to the reaction run without salt, where the competitive formation of the benzyl carbamate is favored, the phosphonium salt promotes high selectivity toward the benzylated amine and an increase of the reaction rate as well. However, in a single case explored for an amino acidic compound, namely 4-(aminomethyl)benzoic acid [4-(NH(2)CH(2))C(6)H(4)CO(2)H], both N,N-dibenzylation and esterification of the acid group were observed. Analysis of the IR vibrational modes of benzylamine in the presence of tetrabutylphosphonium bromide supports the hypothesis that this enhanced selectivity may be due to an acid-base interaction between the salt and the amine, which increases the steric bulk of the amine and favors attack of the nucleophile on the less hindered alkyl terminus of dibenzyl carbonate.

Reaction of functionalized anilines with dimethyl carbonate over NaY faujasite. 3. chemoselectivity toward mono-N-methylation.

In the presence of NaY faujasite, dimethyl carbonate (MeOCO(2)Me, DMC) is a highly chemoselective methylating agent of functionalized anilines such as aminophenols (1), aminobenzyl alcohols (2), aminobenzoic acids (3), and aminobenzamides (4). The reaction proceeds with the exclusive formation of N-methylanilines without any concurrent O-methylation or N-/O-methoxy carbonylation side processes. Particularly, only mono-N-methyl derivatives [XC(6)H(4)NHMe, X = o-, m-, and p-OH; o- and p-CH(2)OH; o- and p-CO(2)H; o- and p-CONH(2)] are obtained with selectivity up to 99% and isolated yields of 74-99%. DMC, which usually promotes methylations only at T > 120 degrees C, is activated by the zeolite catalyst and it reacts with compounds 1, 2, and 4, at 90 degrees C. Aminobenzoic acids (3) require a higher reaction temperature (> or =130 degrees C).