Nucleophilic substitution phase-transfer-catalyzed

The utilization of polar polymers and novel N-alkyl-4-(N, N -dialklamino)pyridinium sedts as stable phase transfer catalysts for nucleophilic aromatic substitution are reported. Polar polymers such as poly (ethylene glycol) or polyvinylpyrrolidone are thermally stable, but provide only slow rates. The dialkylaminopyridininium salts are very active catalysts, and are up to 100 times more stable than tetrabutylammonium bromide, allowing recovery and reuse of catalyst. The utilization of b is-dialkylaminopypridinium salts for phase-transfer catalyzed nucleophilic substitution by bisphenoxides leads to enhanced rates, and the requirement of less catalyst. Experimental details are provided. 

It is comparable to crown ethers or R4NBr for phase-transfer catalyzed aliphatic nucleophilic substitutions in addition it catalyzes aromatic nucleophilic substitutions such as the Ullmann synthesis. 

New asymmetric polymetallic catalysts were reported for the ring-opening reaction of ffieso-aziridines with TMSCN <07T5820>. Three contiguous tertiary stereocenters were generated via the reaction of active methylene nucleophiles with tosylated aziridines under mild phase-transfer catalyzed conditions. For example, reaction of aziridine 61 with the anion derived from 62 provided substituted cyclopentane 63 in excellent yield <07OL4677>. 

Phase transfer catalysis is nowadays a well-established technique in preparative chemistry. However, it has been confined almost exclusively to nucleophilic substitution reactions. Nevertheless some examples of phase transfer catalyzed azo coupling ructions ate known. 

S. Cao and R. Roy, Phase-transfer catalyzed anomeric nucleophilic substitutions occur by an SN2-type mechanism, Carbohydr. Lett., 2 (1996) 27-34. 

Albanese. D. Landini, D. Maia. A. Penso. M. Key role of water for nucleophilic substitutions in phase-transfer-catalyzed processes A mini-review. Ind. Eng. Chem. Res. 2001. 40. 2396-2401. 

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. 

Reaction rates of phase transfer catalyzed nucleophilic displacement reactions depend upon stirring speed.Tomoi studied the effect of stirring speed on the rate of reaction of 1-bromo-octane with aqueous sodium cyanide using 15-18% ring substituted benzyltributylphosphonium ion catalysts. With toluene as the... 

D. Albanese, D. Landini, A. Maia, and M. Penso, Industrial Engineering Chemistry Research, 40, 2396 (2001). Key Role of Water for Nucleophilic Substitutions in Phase-Transfer-Catalyzed Processes A Mini-Review. 

Nucleophilic Reactions. Useful nucleophilic substitutions of halothiophenes are readily achieved in copper-mediated reactions. Of particular note is the ready conversion of 3-bromoderivatives to the corresponding 3-chloroderivatives with copper(I)chloride in hot /V, /V- dim ethyl form am i de (26). High yields of alkoxythiophenes are obtained from bromo- and iodothiophenes on reaction with sodium alkoxide in the appropriate alcohol, and catalyzed by copper(II) oxide, a trace of potassium iodide, and in more recent years a phase-transfer catalyst (27). 

Onium salts, such as tetraethylammonium bromide (TEAB) and tetra-n-butylammonium bromide (TBAB), were also tested as PTCs immobilized on clay. In particular, Montmorillonite KIO modified with TBAB efficiently catalyzed the substitution reaction of a-tosyloxyketones with azide to a-azidoketones, in a biphasic CHCI3/water system (Figure 6.13). ° The transformation is a PTC reaction, where the reagents get transferred from the hquid to the solid phase. The authors dubbed the PTC-modified catalyst system surfactant pillared clay that formed a thin membrane-hke film at the interface of the chloroform in water emulsion, that is, a third liquid phase with a high affinity for the clay. The advantages over traditional nucleophilic substitution conditions were that the product obtained was very pure under these conditions and could be easily recovered without the need for dangerous distillation steps. 

Phase transfer was used to catalyze nucleophilic aromatic substitutions by Makosza et al. in 1974.201 202 Zoltewicz203 has given a good early review of various methods and has compared other techniques that make use of polar solvents, transition metals, and monoelectron transfers. 

Various nucleophiles substitute cyclic sulfamidates such as 521 at C(5) at room temperature and provide good yields of 522, e.g., <1996S259, 1999J(P1)1421, 1999TL3831, 2002TL1915>. The introduction of the N-substitutent to make compounds like 521 is best achieved via a base-catalyzed phase-transfer method or using the Mitsunobu protocol <2002JOC5164>. 

Of course, aziridines can also be synthesized by the ring-closing reactions of appropriately substituted amines. For example, halohydrins of type 142 are converted to iV-hydroxy-aziridines 144 by treatment with hydroxylamine derivatives, followed by base-catalyzed intramolecular Sn2 reaction of the intermediate p-haloaminoesters 143 under phase-transfer conditions <03TL3259>. A -Bromoethylimines 146, formed from the reaction of benzaldehyde derivatives (e.g., 145) and 2-bromo-2-methylpropylamine hydrobromide, undergo nucleophilic attack by methoxide, followed by intramolecular displacement of bromide to form A -(a-methoxybenzyl)aziridines 147 <03TL1137>. 

Reactions with Sulfur Nucleophiles. The use of sulfur nucleophiles in palladium-catalyzed allylic substitution reactions is less well documented than that of carbon, nitrogen and oxygen nucleophiles. The asymmetric synthesis of allylic sulfones utilizing a catalytic phase transfer system has been used to produce (35)-(phenylsulfonyl)cyclohex-l-ene on a 45 g scale (eq 10). In many cases, it has been reported that allylic carbonates are more reactive than allylic acetates in asymmetric allylic substitution... 

The pyridinyl- and 1-oxypyridinyl-substituted silanes and siloxanes were patented as IPTC catalysts in transacylation reactions [178]. In the IPTC nucleophilic substitution reaction of benzoyl chloride with KSCN catalyzed by cyclic and acyclic sulfides such as tetrahydrothiophene and diethyl sulfides, etc., the active ionic intermediate, benzylsulfo-nium ion, formed by benzyl chloride and sulfide in the organic phase, transferred into the aqueous phase to react with thiocyanate ion to produce benzylthiocyanate [179]. In the following discussion, selected IPTC systems are presented, focusing on the kinetic and mechanistic aspects. 

A typical LLPTC cycle involves a nucleophilic substitution reaction, as shown in Eq. (8). A difficult problem in the kinetics of PT-catalyzed reactions is to sort out the rate effects due to equilibrium anion-transfer mechanism for transfer of anions from the aqueous to the organic phase. The reactivity of the reaction by PTC is controlled by the rate of reaction in the organic phase, the rate of reaction in the aqueous phase, and the mass transfer steps between the organic and aqueous phases [27-29]. In general, one assumes that the resistances of mass transfer and of chemical reaction in the aqueous phase can be neglected for a slow reaction in the organic phase by LLPTC. 

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