Carboxylic acids phase transfer

Less rigorous reaction conditions are required to cleave the double bond to form ketones and carboxylic acids. Phase-transfer-assisted permanganate oxidations in the presence of quaternary ammonium salts,439 652-654 crown ethers,439,655 or polyethers566 usually ensure high yields. Terminal alkenes are transformed to carboxylic acids with one carbon atom less than the starting compound.653,654... 

Since 1-aikynes are relatively resistant to oxidation, strong oxidants are required to effect oxidative cleavage of terminal aikynes to carboxylic acids with loss of one carbon. lodosylbenzene in combination with Ru catalysts or potassium perman-ganate cleaves 1-aikynes to carboxylic acids. Phase transfer agents (quaternary ammonium salts ) are used in the KMn04 oxidations to overcome problems associated with the low solubility of permanganate in nonpolar solvents. 

Carboxylation. Under phase-transfer conditions, propargyl and allenyl halides in the presence of CO and Ni(CN)2 are converted into allenic acids. Further reaction gives rise to 2-alkylidenesuccinic acids. 

There are other published resolutions of 4-hydroxyphenylglycine, one of which involves the enzyme-catalysed hydrolysis of the ethyl ester (Scheme 6.9). Since the substrate is fully blocked at the amino and the carboxylate functions, it is scarcely soluble in water and must be dissolved in an organic solvent. The specific hydrolysis of the ester catalysed by an enzyme in an aqueous phase in contact with the organic solvent will yield a water-soluble carboxylic acid which transfers to the aqueous phase containing the enzyme. The conditions of the reaction therefore effect both hydrolysis of the ester and facile separation of the product. In fact, the enzyme is immobilized on a hydrophilic membrane at the interface between the two immiscible phases. The membrane reactor (Figure 6.2) comprises a large bundle of hollow fibres, each having an external diameter of about... 

Naphthaleneacetic acid has also been prepared by the carbonyl-insertion reaction of 1-chloromethylnaphthalene cataly2ed by carbonyl cobalt cation (90,91). Carboxylation of 1-chloromethylnaphthalene in the presence of the catalyst Pd[P(CgH )2]2Cl2 under phase-transfer conditions gave 1-naphthaleneacetic acid in 78% yield (92). 

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... 

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- ... 

Unsymmetrical as well as symmetrical anhydrides are often prepared by the treatment of an acyl halide with a carboxylic acid salt. The compound C0CI2 has been used as a catalyst. If a metallic salt is used, Na , K , or Ag are the most common cations, but more often pyridine or another tertiary amine is added to the free acid and the salt thus formed is treated with the acyl halide. Mixed formic anhydrides are prepared from sodium formate and an aryl halide, by use of a solid-phase copolymer of pyridine-l-oxide. Symmetrical anhydrides can be prepared by reaction of the acyl halide with aqueous NaOH or NaHCOa under phase-transfer conditions, or with sodium bicarbonate with ultrasound. 

Palladium complexes also catalyze the carbonylation of halides. Aryl (see 13-13), vinylic, benzylic, and allylic halides (especially iodides) can be converted to carboxylic esters with CO, an alcohol or alkoxide, and a palladium complex. Similar reactivity was reported with vinyl triflates. Use of an amine instead of the alcohol or alkoxide leads to an amide. Reaction with an amine, AJBN, CO, and a tetraalkyltin catalyst also leads to an amide. Similar reaction with an alcohol, under Xe irradiation, leads to the ester. Benzylic and allylic halides were converted to carboxylic acids electrocatalytically, with CO and a cobalt imine complex. Vinylic halides were similarly converted with CO and nickel cyanide, under phase-transfer conditions. ... 

If one of the species is anionic and we need to transport it to the organic phase, then a phase-transfer catalyst may be employed. Consider the example of benzyl penicillin where the reaction between phenyl acetic acid and the penicillin carboxylate ion, with penicillin amidase as a catalyst, is relevant, and which at pH 4.5 - 5.0 is shifted in the desired direction. Here a catalyst like tetrabutylammonium halide works, and with chloroform as a solvent 60% yield can be realized in contrast to a yield of only 5 - 10 % in water. 

Cyanide and thiocyanate anions in aqueous solution can be determined as cyanogen bromide after reaction with bromine [686]. The thiocyanate anion can be quantitatively determined in the presence of cyanide by adding an excess of formaldehyde solution to the sample, which converts the cyanide ion to the unreactive cyanohydrin. The detection limits for the cyanide and thiocyanate anions were less than 0.01 ppm with an electron-capture detector. Iodine in acid solution reacts with acetone to form monoiodoacetone, which can be detected at high sensitivity with an electron-capture detector [687]. The reaction is specific for iodine, iodide being determined after oxidation with iodate. The nitrate anion can be determined in aqueous solution after conversion to nitrobenzene by reaction with benzene in the presence of sulfuric acid [688,689]. The detection limit for the nitrate anion was less than 0.1 ppm. The nitrite anion can be determined after oxidation to nitrate with potassium permanganate. Nitrite can be determined directly by alkylation with an alkaline solution of pentafluorobenzyl bromide [690]. The yield of derivative was about 80t.with a detection limit of 0.46 ng in 0.1 ml of aqueous sample. Pentafluorobenzyl p-toluenesulfonate has been used to derivatize carboxylate and phenolate anions and to simultaneously derivatize bromide, iodide, cyanide, thiocyanate, nitrite, nitrate and sulfide in a two-phase system using tetrapentylammonium cWoride as a phase transfer catalyst [691]. Detection limits wer Hi the ppm range. 

The mesogenic units with methylenic spacers were prepared by reacting the sodium salt of either 4-methoxy-4 -hydroxybiphenyl or 4-phenylphenol with a bromoester in DMF at 82° C for at least 4 hours in the presence of tetrabutylammonium hydrogen sulfate (TBAH) as phase transfer catalyst. In this way, ethyl 4-(4-oxybi-phenyl)butyrate, ethyl 4-(4-methoxy-4 -oxybiphenyl)butyrate, ethyl 4-(4-oxybiphenyl)valerate, ethyl 4-(4-methoxy-4 -oxybiphenyl)-valerate, n-propyl 4-(4-oxybiphenyl)undecanoate and n-propyl 4-(4-methoxy-4 -oxybiphenyl)undecanoate were obtained. These esters were hydrolyzed with base and acidified to obtain the carboxylic acids. The corresponding potassium carboxylates were obtained by reaction with approximately stoichiometric amounts of potassium hydroxide. Experimental details of these syntheses were described elsewhere (27). 

Nickel-catalyzed carbonylation of a-ketoalkynes has also been reported by Arzoumanian et al. under phase-transfer conditions.94 The carbonylation gave either furanone or unsaturated carboxylic acids depending on the substituents of substrates (Eq. 4.53). A similar reaction, nickel-catalyzed cyanation of a-ketoalkynes with KCN in water, was also reported to afford unsaturated hydroxylactams (Eq. 4.54).95... 

An enantioselective synthesis of both (R)- and (5)-a-alkylcysteines 144 and 147 is based on the phase-transfer catalytic alkylation of fert-butyl esters of 2-phenyl-2-thiazoline-4-carboxylic acid and 2-ort/ro-biphenyl-2-thiazoline-4-carboxylic acid, 142 and 145 <06JOC8276>. Treatment of 142 and 145 with alkyl halides and potassium hydroxide in the presence of chiral catalysts 140 and 141 gives the alkylated products, which are hydrolyzed to (R)- and (S)-a-alkylcysteines 144 and 147, respectively, in high enantioselectivity. This method may have potential for the practical synthesis of chiral a-alkylcysteines. 

This methodology provides a general synthesis of L-amino acids in 92-96% ee and in chemical yields of about 40-60%. Thus reaction of 3 (X = Br) with NaN3 under phase-transfer conditions provides 6, which is homologated to the 1-chloro-2-azidoboronate 7. This product is oxidized by sodium chlorite directly to an azido carboxylic acid (8). Hydrogenation of 8 provides L-amino acids (9). 

Preparation of the donor 46 was started from 4,6-0-benzylidene protected thiomannoside 47 (Scheme 7.24). Alkylation with p-allyloxybenzyl chloride under phase transfer conditions78 was followed by 3-O-silylation and Pd(0)-mediated deallylation79 to give 48. The phenolic OH group was alkylated with ethyl 6-bromohexanoate and carboxylic acid, liberated by alkaline hydrolysis, was reacted with PEG monomethyl ether (MW -5000) under Mitsunobu conditions to afford 46. 

Aside from alkoxycarbonylations, hydroxycarbonylations in the presence of water to yield allenic carboxylic acids [15] (93, Y = OH) and aminocarbonylations in the presence of amines to give the analogous amides [139] (93, Y = NRR ) have also been carried out, respectively (Scheme 7.13). These products of structure 102 can also be obtained if using the propargylamines 101 with R1 = Ph or R3 Z H as starting materials (Scheme 7.15) [140]. Additionally, hydroxycarbonylations, also termed carboxyla-tions, are successful without palladium catalysis by reaction of propargyl halides and carbon monoxide in the presence of nickel(II) cyanide under phase-transfer conditions [141, 142]. 

The ability of quaternary ammonium halides to form weakly H-bonded complex ion-pairs with acids is well established, as illustrated by the stability of quaternary ammonium hydrogen difluoride and dihydrogen trifluorides [e.g. 60] and the extractability of halogen acids [61]. It has also been shown that weaker acids, such as hypochlorous acid, carboxylic acids, phenols, alcohols and hydrogen peroxide [61-64] also form complex ion-pairs. Such ion-pairs can often be beneficial in phase-transfer reactions, but the lipophilic nature of H-bonded complex ion-pairs with oxy acids, e.g. [Q+X HOAr] or [Q+X HO.CO.R], inhibits O-alkylation reactions necessitating the maintenance of the aqueous phase at pH > 7.0 with sodium or potassium carbonate to ensure effective formation of ethers or esterification [49,64]. 

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]. 

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