Reactions polar protic media

For the Michael addition between 3-pentanone and nitrostyrene a report by Patil and Sunoj points out a key limitation of the standard enamine derived transition state model when a polar protic reaction medium is employed (Scheme 17.10) [42]. The unassisted transition state inclusive of continuum solvent effects failed to predict the correct stereochemical outcome of the reaction as compared to the experimental observations. The predicted lowest energy transition state has been identified as leading to an incorrect configuration of the newly formed chiral centers as well as the wrong diastereomer. Further refinements to the transition state models were carried out with inclusion of explicit solvent molecules in view of the fact that the reaction being modeled has been conducted in methanol as the solvent. After examining several microsolvated transition states with varying... 

Alkali moderation of supported precious metal catalysts reduces secondary amine formation and generation of ammonia (18). Ammonia in the reaction medium inhibits Rh, but not Ru precious metal catalyst. More secondary amine results from use of more polar protic solvents, CH OH > C2H5OH > Lithium hydroxide is the most effective alkah promoter (19), reducing secondary amine formation and hydrogenolysis. The general order of catalyst procUvity toward secondary amine formation is Pt > Pd Ru > Rh (20). Rhodium s catalyst support contribution to secondary amine formation decreases ia the order carbon > alumina > barium carbonate > barium sulfate > calcium carbonate. 

The reaction medium also plays a key role in the overall activity of the catalyst system. The reaction rate is highly dependent on the nature of the medium however, the overall kinetics are unaffected by reaction solvent [5c, 27, 30-32]. This suggests that the rate dependence of the solvent is not involved in the transition-state species of the rate-determining step [5c]. Maximum carbonylation rates are demonstrated in polar solvents and the additions of protic solvents accelerate... 

Coordination of the anions to the cationic palladium center may strongly depend on the polarity of the reaction medium. Solvation of the ion-pair by protic solvent molecules, such as methanol, is expected to facilitate cation-anion dissociation and therefore render the metal center more electrophilic and more easily accessible for substrate molecules. In relatively apolar solvents, close-contact ion-pairs are generally expected to exist. Anion displacement by substrate molecules may then require the use of noncoordinating anions, such as certain tetraaryl borates [19], with a relatively strong affinity for interaction with the solvent molecules. This will lead to a reduced barrier for displacement of these anions by monomer molecules. 

A related and well-known but effectively unquantified phenomenon is that POM lability is greatly reduced in organic solvents. The addition of even small percentages of either polar protic solvents such as alcohols or polar aprotic solvents such as acetonitrile, DMF, and DMSO to aqueous solutions of POMs greatly reduces the rate of POM reactions.1 7,152,159-162 The medium one is using impacts the rates of intramolecular processes such as rearrangements and isomeriza-tions as well as intermolecular processes. 

The low conversion obtained in acetic acid is probably due to the strong hydrogen bond, which occurs between the hydroxyl group of the protic solvent and the O-H group present in NHPI, thus inhibiting the molecule-induced homolysis effect. However, a polar solvent is required to make NHPI soluble in the reaction medium that is why the conversion decreases in dichloroethane, whereas no product is observed in Ph-CFs, where the organocatalyst remains in suspension. 

Coordination of the anions to the cationic palladium center may strongly depend on the polarity of the reaction medium. Solvation of the ion-pair by protic solvent molecules, such as methanol, is expected to fadhtate cation-anion dissociation... 

The first choice for a solvent during the development of a synthetic procedure is usually an organic liquid, which is selected on the basis of its protic or aprotic nature, its polarity, and the temperature range in which the reaction is expected to proceed. Once the desired transformation is achieved, yield and selectivity are further optimized in the given medium by variation of temperature, concentration, and related process parameters. At the end of the reaction, the solvent must be removed quantitatively from the product using conventional workup techniques like aqueous extraction, distillation, or chromatography. If the synthetic procedure becomes part of a large-scale application, the solvent can sometimes be recycled, but at least parts of it will ultimately end up in the waste stream of the process. 

The type of solvent or diluent should be specified in reporting a Ziegler-Natta catalyst system. Alkene polymerisations are usually carried out in inert solvents, such as aliphatic or aromatic hydrocarbons (e.g. some gasoline fractions or toluene). The use of protic or aprotic polar solvents or diluents instead of the hydrocarbon polymerisation medium can drastically alter the reaction mechanism. This usually results in catalyst deactivation for alkene coordination polymerisation. Modern alkene polymerisation processes are carried out in a gas phase, using fluidised-bed catalysts, and in a liquid monomer as in the case of propylene polymerisation [28,37]. 

Other examples of this type of reaction are Sn2 reactions between azide ion and 1-bromobutane [67], bromide ion and methyl tosylate [68], and bromide ion and iodoethane [497]. In changing the medium from non-HBD solvents (HMPT, 1-methylpyrrolidin-2-one) to methanol, the second-order rate constants decrease by a factor of 2 10 [67], 9 10 [68], and 1 10 [497], respectively. The large decrease in these rate constants in going from the less to the more polar solvent is not only governed by the difference in solvent polarity, as measured by dipole moment or relative permittivity, but also by the fact that the less polar solvents are dipolar aprotic and the more polar solvents are protic cf. Section 5.5.2). 

The reaction is experimentally simple either the halide is heated with hexamethylenetetraamine (HMTA) in a polar solvent such as aqueous acetic acid, or, with unreactive halides, the quaternary salt is first prepared in chloroform and then decomposed in a protic medium. The reaction is believed to proceed as shown in Scheme 11. 

Bromine Addition to Alkenes. Alumina can advantageously replace protic solvents thus avoiding secondary reactions due to their nucleophdicity. This situation is evidenced in the bromation of alkenes [14]. When performed in methanol, bromine addition leads to a mixture of a frans-dibromo adduct and a trans-bromo ether compound. The latter results from competitive attack by pro-tic solvent on the bromonium ion intermediate. This byproduct can be suppressed using Br2/alumina, as the support behaves as a non-nucleophilic polar medium (Scheme 3). 

The solvent dependence of this cycloaddition is remarkable. The formation of 5 requires an aprotic medium, whereas in a protic medium (e.g. CH3OH), the thieno[2,3-Z ]-5,6,7,7a-tetrahydro-l -pyrrolizine 10 is formed. As the rate of product formation is the same in both media, it is plausible that the same primary product 8 of a dipolar [2+2] cycloaddition is formed first. The reaction then proceeds to give 5 in the nonpolar medium and 10 via the ylide 9 in the polar medium [19]. 

In the Monsanto process methanol and CO react continuously in the liquid phase at 180 °C and 30 bar in the presence of a Rhl2 catalyst. Since the intermediates are anionic complexes and the reaction rate is enhanced by protic solvents, the reaction is carried out in polar solvents (e.g., acetic add/water medium). The main byproducts are CO2 and H2 formed with water [(6.15.4), water-gas-shift-reaction]. 

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