Phase-transfer catalysis chlorides

The benzoic acid derivative 457 is formed by the carbonylation of iodoben-zene in aqueous DMF (1 1) without using a phosphine ligand at room temperature and 1 atm[311]. As optimum conditions for the technical synthesis of the anthranilic acid derivative 458, it has been found that A-acetyl protection, which has a chelating effect, is important[312]. Phase-transfer catalysis is combined with the Pd-catalyzed carbonylation of halides[3l3]. Carbonylation of 1,1-dibromoalkenes in the presence of a phase-transfer catalyst gives the gem-inal dicarboxylic acid 459. Use of a polar solvent is important[314]. Interestingly, addition of trimethylsilyl chloride (2 equiv.) increased yield of the lactone 460 remarkabiy[3l5]. Formate esters as a CO source and NaOR are used for the carbonylation of aryl iodides under a nitrogen atmosphere without using CO[316]. Chlorobenzene coordinated by Cr(CO)j is carbonylated with ethyl formate[3l7]. 

In specific applications to phase transfer catalysis, Knbchel and his coworkers compared crown ethers, aminopolyethers, cryptands, octopus molecules ( krakenmole-kiile , see below) and open-chained polyether compounds. They determined yields per unit time for reactions such as that between potassium acetate and benzyl chloride in acetonitrile solution. As expected, the open-chained polyethers were inferior to their cyclic counterparts, although a surprising finding was that certain aminopolyethers were superior to the corresponding crowns. 

Reaction of 4-hydroxyquinoline-2-one 598 with oxalyl chloride gave oxazoloquinoline 599 (970PP211). The oxazoloquinoline 600 was obtained as a byproduct during the synthesis of pyranoquinoline alkaloids 601 by reaction of 598 with 2-methyl-2-chlorobutyne under phase transfer catalysis (87JHC869) (Scheme 101). 

Another two-phase system using phase-transfer catalysis for the oxidation of diaryl-iV-arylsulphonyl sulphilimines to sulphoximines has also been described188. In this reaction the oxidizing reagent is sodium hypochlorite and yields are in excess of 90% in most cases (equation 70). This reaction presumably occurs by initial attack by the nucleophilic hypochlorite ion on the sulphur atom followed by chloride ion elimination. 

Quaternary ammonium compounds (quats) are prepared - by moderate heating of the amine and the alkyl halide in a suitable solvent - as the chlorides or the bromides. Subsequently conversion to the hydroxides may be carried out. Major applications of the quat chlorides are as fabric softeners and as starch cationizing agent. Several bio-active compounds (agrochemicals, pharmaceuticals) possess the quat-structure. Important applications of quat bromides are in phase transfer catalysis and in zeolite synthesis. 

This reaction is similar to 13-1 and, like that one, generally requires activated substrates. With unactivated substrates, side reactions predominate, though aryl methyl ethers have been prepared from unactivated chlorides by treatment with MeO in HMPA. This reaction gives better yields than 13-1 and is used more often. A good solvent is liquid ammonia. The compound NaOMe reacted with o- and p-fluoronitrobenzenes 10 times faster in NH3 at — 70°C than in MeOH. Phase-transfer catalysis has also been used. The reaction of 4-iodotoluene and 3,4-dimethylphenol, in the presence of a copper catalyst and cesium carbonate, gave the diaryl ether (Ar—O—Ar ). Alcohols were coupled with aryl halides in the presence of palladium catalysts to give the Ar—O—R ether. Nickel catalysts have also been used. ... 

In the mid-1960s a series of papers by Makosza and Serafinowa (1965, 1966) appeared under the common title Reactions of Organic Anions , in which the catalytic alkylation of phenylacetonitrile and its derivatives carried out in the presence of concentrated NaOH and the catalyst triethylbenzylammonium chloride (TEBA) was described. This was the beginning of phase-transfer catalysis (PTC), and since then thousands of papers haven been published on the subject. 

These reactions proceed more rapidly in polar aprotic solvents. In DMSO, for example, primary alkyl chlorides are converted to nitriles in 1 h or less at temperatures of 120°-140°C.36 Phase transfer catalysis by hexadecyltributylphosphonium bromide permits conversion of 1-chlorooctane to octyl cyanide in 95% yield in 2 h at 105° C.37... 

Loupy and Soufiaoui described a comparative study of the reactivity of diphenylnitri-limine 200 with several dipolarophiles under microwave irradiation in the absence of solvent using a solid mineral support or phase-transfer catalysis (PTC) conditions (Scheme 9.62) [30b]. The results showed that the best yields of adducts were achieved upon impregnating KF-alumina with a mixture of the hydrazynoyl chloride 199 and the dipolarophile followed by irradiation of the mixture in a focused oven. Reaction of this mixture under solid-liquid PTC conditions with KF-Aliquat under microwaves afforded lower yields of cycloadducts, perhaps owing to the partial decomposition of Aliquat at the reaction temperature (140 °C). In all cases, worse yields were obtained by classical heating under comparable reaction conditions (time and temperature). 

Phosphorylation of phenolate anions with dimethyl phosphorochloridothionate in water-dichloromethane systems normally gives large amounts of dithiopyrophos-phate because of extensive hydrolysis of the phosphorus chloride, but in the presence of tetrabutylammonium salts and 1 % imidazole, phosphorylation of the phenolate anion is complete. The explanation lies in an evident combination of activation of acylating agent (by imidazole) and of nucleophile (by phase-transfer catalysis).71... 

E-(P-Alkylvinyl)phenyliodonium salts react with tetra-n-butylammonium halides to yield the correspondingly substituted Z-haloethenes (80-100% for chloro-, bromo- and iodo-derivatives) [41], In contrast, in the corresponding reaction with Z-(2-benzenesulphonyl-ethenyl)phenyliodonium salts, nucleophilic substitution occurs with retention of configuration to yield the Z-2-benzenesulphonyl-l-haloethenes [42], The ammonium fluorides fail to yield the fluoroethenes, but produce the ethynes by simple elimination [41]. Where carboxylic acids have low solubility in organic solvents, their conversion into the acid chlorides is frequently difficult. Phase-transfer catalysis not only allows the conversion to be effected rapidly, it also results in high yields of a wide range of acid chlorides [43]. 

Sulphonic esters have been obtained from the sulphonyl chlorides in high yields under mild conditions for a range of alcohols and phenols [e.g. 18, 19]. Of particular value is the protection of glycosides possessing a free hydroxyl group and hydroxy-steroids, which are tosylated readily under phase-transfer conditions [20-22]. Alkyl sulphinites have been obtained in a similar manner [23]. Alternatively, preformed tetra-rt-butylammonium sulphonates or their alkali metal salts have also been alkylated with haloalkanes or alkyl fluorosulphonates [24,25]. In contrast with more classical procedures, tosylation of alcohols, which are susceptible to E/Z-isomerism, e.g. Z-alk-2-en-l-ols, occurs with retention of their stereochemistry under phase-transfer catalysis [26]. 

Allyl chlorides and bromides are readily carbonylated to unsaturated acids using nickel cyanide and phase transfer catalysis conditions. Mechanistic studies revealed that the key catalytic species in this reaction is the cyanotricarbonylnickelate ion(20). 

Glycosyl halides (7a-e) were stereoselectively transformed into l,2-tra s-thio-glycoses by i) (8a-d, 8j) a two-step procedure via the pseudothiourea derivatives [9,10a] the substitution of halide by thiourea is mostly a S l-type reaction since acetylated 1-thio-a-D-mannose (8b) was obtained from acetobromoman-nose (7b) [9cj ii) (8e-i) using thiolates in protic and aprotic solvents [10], or under phase transfer catalysis conditions [11]. Another approach involved the reaction of thioacetic acid with 1,2-trans-per-O-acetylated glycoses catalyzed with zirconium chloride [12]. The 1,2-trans-peracetylated 1-thioglycoses (8e-h) were obtained in high yield. No anomerized products could be detected in these reactions (Fig. 1). 

Phase-transfer catalysis was found <1996CHEC-II(7)1> to be successful for N-substitution of the furo[3,2-/ ]pyrrole system. The reaction of 81a with methyl iodide or benzyl chloride gave 81b and 81c derivatives. Methyl 4-acetyl-2-[3-(trifluoromethyl)phenyl]furo[3,2-3]pyrrole-5-carboxylate 82 was obtained by reacting 81a in boiling acetic anhydride (Scheme 6) <2005CEC311>. 

HCA121). 3-Acetyl-4-hydroxy-l,5,5-trimethyl-2-pyrrolone 39a gives no acetylated products with either benzoyl chloride or benzoic anhydride, or acetic anhydride. By contrast phase-transfer catalysis (K2C03/CHC13 r.t.) affords a condensation product, formed from two molecules, 39a. This product does not bear a benzoyl group (87TH2). 

Classical Phase Transfer assisted Organometallic Catalysis588"601 is a further important field which has found industrial applications e.g. in the carbonylation of benzyl chloride to phenylacetic acid using NaCo(CO)4/Bu4NBr catalysts in aqueous NaOH practiced by Montedison.52,466,589,596,601 However, a detailed discussion of classical phase transfer catalysis is beyond the scope of this chapter which is devoted to systems in which the catalytic conversion takes place in the aqueous phase. 

Di Cesare and Gross175 introduced a procedure using phase-transfer catalysis to induce the action of dichlorocarbene on various protected sugars,176 and obtained the chloro derivative 162c from compound 161. Another, similar migration was observed,178 and confirmed,134,174 for the chlorination of methyl 2,3-anhydro-4,6-0-benzylidene-a-D-al-lopyranoside (166) with (chloromethylene)dimethyliminium chloride, which gave the rearranged chloro derivative 167. 

While polar protic solvents, such as MeOH, strongly retard reaction,33 phase transfer catalysis using benzene34 or addition of crown ethers to potassium alkoxides in benzene33 allows reaction at 25 C. Even with strong electron donors, such as alkyl, methoxy or dialkylamino in the ortho, meta or para positions, substitution for chloride by potassium methoxide proceeds smoothly using the crown ether activation in benzene (equation 8).33... 

Undoubtedly the most important and widely used procedure for the generation of dichlorocarbene involves the reaction of chloroform with aqueous sodium hydroxide under the conditions of phase transfer catalysis (PTC), introduced by Makosza.20-22 Under these conditions chloroform reacts with sodium hydroxide to form sodium trichloromethylide which on exchange with a quaternary ammonium salt, usually benzyltriethylammonium chloride, is converted to the unstable quaternary ammonium methylide which dissociates in the organic phase to give dichlorocarbene. The dichlorocarbene irreversibly adds to the alkene (Scheme 1). 

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