Nucleophilic groups phase-transfer-catalyzed

A carboxylic acid (not the salt) can be the nucleophile if F is present. Mesylates are readily displaced, for example, by benzoic acid/CsF. Dihalides have been converted to diesters by this method. A COOH group can be conveniently protected by reaction of its ion with a phenacyl bromide (ArCOCH2Br). The resulting ester is easily cleaved when desired with zinc and acetic acid. Dialkyl carbonates can be prepared without phosgene (see 10-21) by phase-transfer catalyzed treatment of primary alkyl halides with dry KHCO3 and K2C03- ... 

Three major topics of research which are based on phase transfer catalyzed reactions will be presented with examples. These refer to the synthesis of functional polymers containing functional groups (i.e., cyclic imino ethers) sensitive both to electrophilic and nucleophilic reagents a novel method for the preparation of regular, segmented, ABA triblock and (A-B)n alternating block copolymers, and the development of a novel class of main chain thermotropic liquid-crystalline polymers, i.e., polyethers. 

Asymmetric phase-transfer catalyzed cascades initiated by the conjugate addition of heteronucleophiles has been employed for the enantioselective preparation of epoxides and aziridines using a suitable oxygen- or nitrogen-based nucleophile incorporating an appropriate leaving group ready to... 

Development Center achieved this in the late 1970s [10], An important feature of this invention was the development of a process to make dianhydrides, specifically dianhydrides based on bisphenol-A. This was achieved by phase-transfer-catalyzed nucleophilic aromatic substitution, as shown in Eq. (8.4). Anitro group was displaced from a phthal-imide by a bisphenol salt to yield a difunctional imide compound, which, in turn, was converted to the bisphenol-A dianhydride (BPADA). Sodium nitrite is made as a by-product. 

In a subsequent study (345), this group examined the detailed mechanism of a solid salt/SCF phase transfer-catalyzed reaction. They selected a reaction similar to that depicted in Figure 11, that of the irreversible nucleophilic displacement of benzyl chloride with potassium cyanide to form phenylacetonitrile and potassium chloride. The study primarily used the catalyst THAB as in the previous study. The effects of various factors on the reaction kinetics were investigated, including the amount of catalyst, the amount of KCN, the presence of acetone cosolvent, and temperature. Measured kinetic data were consistent with irreversible pseudo-first-order kinetics in the catalyst concentration. However, the reaction rate was found to be linearly dependent on the catalyst concentra-... 

We have also recently described the use of a polystyrene resin with pendant sulflnate groups (Ref. 64) in phase transfer catalyzed reactions with various electrophiles. The reactions afford sulfones in excellent yields, often nearly quantitative, even though sulfinates are not reputed to be very good nucleophiles. In contrast, the same reactions without any added phase transfer catalyst give only very low conversions. The sulfinate resins have also been used extensively in a number of Michael additions and have proved to be excellent for use as regenerable separation media in the removal of allergenic substances from some plant extracts used in the perfume and cosmetics Industry (Ref. 61, 62). 

The reaction between acyl halides and alcohols or phenols is the best general method for the preparation of carboxylic esters. It is believed to proceed by a 8 2 mechanism. As with 10-8, the mechanism can be S l or tetrahedral. Pyridine catalyzes the reaction by the nucleophilic catalysis route (see 10-9). The reaction is of wide scope, and many functional groups do not interfere. A base is frequently added to combine with the HX formed. When aqueous alkali is used, this is called the Schotten-Baumann procedure, but pyridine is also frequently used. Both R and R may be primary, secondary, or tertiary alkyl or aryl. Enolic esters can also be prepared by this method, though C-acylation competes in these cases. In difficult cases, especially with hindered acids or tertiary R, the alkoxide can be used instead of the alcohol. Activated alumina has also been used as a catalyst, for tertiary R. Thallium salts of phenols give very high yields of phenolic esters. Phase-transfer catalysis has been used for hindered phenols. Zinc has been used to couple... 

The affinity of the polymer-bound catalyst for water and for organic solvent also depends upon the structure of the polymer backbone. Polystyrene is nonpolar and attracts good organic solvents, but without ionic, polyether, or other polar sites, it is completely inactive for catalysis of nucleophilic reactions. The polar sites are necessary to attract reactive anions. If the polymer is hydrophilic, as a dextran, its surface must be made less polar by functionalization with lipophilic groups to permit catalytic activity for most nucleophilic displacement reactions. The % RS and the chemical nature of the polymer backbone affect the hydrophilic/lipophilic balance. The polymer must be able to attract both the reactive anion and the organic substrate into its matrix to catalyze reactions between the two mutually insoluble species. Most polymer-supported phase transfer catalysts are used under conditions where both intrinsic reactivity and intraparticle diffusion affect the observed rates of reaction. The structural variables in the catalyst which control the hydrophilic/lipophilic balance affect both activity and diffusion, and it is often not possible to distinguish clearly between these rate limiting phenomena by variation of active site structure, polymer backbone structure, or % RS. 

The first step of this method involves a Knoevenagel-type condensation of TosMIC to provide intermediate 36a [28], It is noteworthy that the conditions used helped (a) cope with the lower activity of the 17-oxo group of 35 and (b) avoid elimination of sulfinic acid. The second step involves the condensation of 36a with formaldehyde (9c) to form intermediate 38, which then undergoes an internal nucleophilic attack onto the isocyanide carbon to generate the oxazoline intmnediate 39. Addition of 10 equivalents of MeOH to the phase transfer catalyst directly generates oxazoline 41 via the elimination of tosyl sulfonic acid from 40. Acid-catalyzed hydrolysis provides the target compound 37 (Scheme 7.8). 

Catalytic mono-oxygen transfer from first row transition metals to nucleophilic substrates has been the subject of intensive studies since the late seventies [1-2]. The classic procedures of porphyrin-catalyzed oxidations have however obvious disadvantages [3-6]. Chlorinated solvents are often used, either in a two phase system or as co-solvents to dissolve the porphyrin. The reaction mixtures are heavily colored. Catalyst recuperation is not obvious, and often the porphyrin doesn t even survive a single catalytic run. Several groups have attempted with varying success to improve the usability of porphyrins by diverse heterogenization techniques [7-10]. 

The question of interest is whether the ions produced in this manner behave like their counterparts in solution, which are the conjugate acids of the parent carboxyl derivative. In particular, do they react with added nucleophiles to transfer the acyl group in a manner related to acid-catalyzed acyl transfer commonly observed in condensed phase ... 

---