Extractive alkylation

Derivatization (GC) 848 alkylating reagents 861 alkyl halide/catalyst 861 dialkyl acetals 863 diazoalkanes 862 extractive alkylation 863 pyrolytic alkylation 865 al) ldimethylsilyl reagents 855... 

Extractive alkylation is used to derivatize acids, phenols, alcohols or amides in aqueous solution [435,441,448,502]. The pH of the aqueous phase is adjusted to ensure complete ionization of the acidic substance which is then extracted as an ion pair with a tetraalkylammonium hydroxide into a suitable immiscible organic solvent. In the poorly solvating organic medium, the substrate anion possesses high reactivity and the nucleophilic displacement reaction with an alkyl halide occurs under favorable conditions. 

Hattori [77] extracted alkyl and alkyltin compounds from sediments with methanoic hydrochloric acid and then, following mixture with sodium chloride and water, the mixture was extracted with benzene and converted to hydrides with sodium borohydride and analysed by gas chromatography using an electron capture detector. Down to 0.02mg kg 1 organotin compounds in sediments could be determined with a recovery of 70-95%. 

Bradway DE, Moseman R, May R. 1981. Analysis of alkyl phosphates by extractive alkylation. Bull Environ Contam Toxicol 26 520-523. 

In the main, the original extractive alkylation procedures of the late 1960s, which used stoichiometric amounts of the quaternary ammonium salt, have now been superseded by solid-liquid phase-transfer catalytic processes [e.g. 9-13]. Combined soliddiquid phase-transfer catalysis and microwave irradiation [e.g. 14-17], or ultrasound [13], reduces reaction times while retaining the high yields. Polymer-supported catalysts have also been used [e.g. 18] and it has been noted that not only are such reactions slower but the order in which the reagents are added is important in order to promote diffusion into the polymer. 

Methylenesulphones are more acidic than the simple esters, ketones and cyano compounds and are more reactive with haloalkanes [e.g. 48-57] to yield precursors for the synthesis of aldehydes [53], ketones [53], esters [54] and 1,4-diketones [55] (Scheme 6.4). The early extractive alkylation methods have been superseded by solidtliquid phase-transfer catalytic methods [e.g. 58] and, combined with microwave irradiation, the reaction times are reduced dramatically [59]. The reactions appear to be somewhat sensitive to steric hindrance, as the methylenesulphones tend to be unreactive towards secondary haloalkanes and it has been reported that iodomethylsulphones cannot be dialkylated [49], although mono- and di-chloromethylsulphones are alkylated with no difficulty [48, 60] and methylenesulphones react with dihaloalkanes to yield cycloalkyl sulphones (Table 6.5 and 6.6). When the ratio of dihaloalkane to methylene sulphone is greater than 0.5 1, open chain systems are produced [48, 49]. Vinyl sulphones are obtained from the base-catalysed elimination of the halogen acid from the products of the alkylation of halomethylenesulphones [48]. 

SYNTHESIS and CHARACTERIZATION of O-ALKYLATED EXTRACTS. Alkylation occurs when tetrabutylanunonium hydroxide is used to promote the reaction of the alkyl iodide with the coal in tetrahydrofuran.(14) The alkylation reaction occurs primarily on acidic oxygen functionalities such as phenolic hydroxyl and carboxylic acid groups, as shown below. 

Ion-pair extraction, or extractive alkylation, is essentially identical to PTC in liquid-liquid systems, but the R4N+ salts are used in stoichiometric quantities. The intermediate R4N + salts of the required anions can be prepared and isolated.14... 

Barbiturates (96) and nitrazepan (97) have been methylated by the extractive alkylation procedure, using ICH3.155,156... 

The extractant s stability can be improved if the selected diluent has a lower ionization potential than the extractant, like aromatic compounds (183). This protective effect has been observed for numerous extractants alkyl phosphates, alkyl phosphonates, amides, and calixarenes (25, 39, 68, 84,... 

Fogelgvist, E., Josefsson, B., and Roos, C., Determination of carboxylic acids and phenols in water by extractive alkylation using pentafluorobenzylation, glass capillary g.c. and electron capture detection, HRC CC, J. High Resolut. Chromatogr. Chromatogr. Commun., 3, 568, 1980. 

W. J. Joem, Confirmation of low concentrations of urinary benzodiazepines, including alprazolam and triazolam by GC/MS an extraction alkylation procedure, J. Anal. Toxicol., 16 363 (1992). 

An example of coordinative extraction with solvating agents is shown in Eq. (4). The difference with physical extraction is that the capacity and extraction power of the liquid neutral ion exchanger is much higher than with any bulk organic solvent (toluene, xylene, butanol, etc.) used in physical extraction. Alkyl-substituted... 

Vp and VL are the volumes of the extraction agent and the liquid sample, respectively, and Kle - Ce/Ce is the distribution coefficient. In practice, an extraction yield higher than 99% is usually considered to be quantitative. With the use of the same volumes of the extraction agent and the sample, this result can be obtained even in a single extraction step if Kle < 0.01. Sometimes the entire procedure can be complicated by a chemical reaction taking place, e.g., in the extractive alkylation (see p.59) or in the preparation of volatile metal chelates (see p.194), and the total yield of the extraction then involves, in addition to the interphase distribution of the initial compounds and products, also the chemical equilibrium which is attained by the reaction. If the quantitative yield of the extraction cannot be predicted on the basis of the character of the system, the extraction efficiency must be determined, otherwise the quantitative evaluation is questionable. 

Extractive alkylation has a reaction scheme identical with that for the previous procedure. The substrate with a carboxyl group reacts in an aqueous solution with a quaternary base and is extracted in the form of an ion pair into a polar solvent of low solvation capacity (dichloromethane) that contains alkyl halide. Low solvation of the anion of the acid and high solvation of the reaction product lead to increased reactivity of the anion and to a rapid reaction with the alkylation agent in the organic phase. Methyl iodide [27] is used to prepare methyl esters and pentafluorobenzyl bromide [28] is used for the preparation of esters providing a high ECD response. 

Oxazepam and related compounds are converted by extractive alkylation into N,0-dimethyl derivatives and are analysed on 3% of OV-225 at 250°C [550]. Another procedure involves the extraction of the sample with benzene, hydrolysis with a strong acid and acylation of the benzophenone amino derivative produced with TFA anhydride [551], Extractive alkylation is used to advantage also for other pharmaceuticals, especially for their determination in plasma, urine and other biological materials. By this procedure hydrochlorothiazide was analysed in plasma, blood corpuscules and urine [552], furosemide in plasma [553] and chlorthalidone and related drugs in plasma and other biological samples [554,555],... 

DTncan, E., and Seyden-Penne, J. 1975. Ion Pair Extraction Alkylation of phosphonates and the Wittig/Horner Reaction. Synthesis 516-517. 

Vartiainen, T., Kauranen, P. (1984). The determination of traces of fluoroacetic acid by extractive alkylation, penta-fluorobenzylation and capillary gas chromatography-mass spectrometry. Anal. Chim. Acta 157 91-7. 

Ethers, Esters, and Related Derivatives of Alcohols.—Oestrogens are effectively methylated at the phenolic oxygen by extraction from alkaline solution into di-chloromethane containing iodomethane, with a tetra-n-hexylammonium salt as a phase-transfer reagent ( extractive alkylation ). Conditions are mild, and the reaction is very rapid. In combination with g.l.c. analysis of the methyl ethers, it provides a simple and convenient method for the analysis of oestrogen mixtures. H-... 

Pentafluorbenzylation of morphine and related phenolic alkaloids by extractive alkylation 54... 

Huhtikangas et al. used also glass capillary columns for quantitative determination of morphine in plasma levels. A relative simple method was developed based on extractive alkylation of morphine with pentafluorobenzyl bromide. A glass capillary, 18 m by o.35 mm I.D. coat ed with 0V-225, and nalorphine as internal standard were used. The detection limit with FID... 

To be able to determine theophylline in the ng range, Arbin and Edlund improved their method by derivatizing theophylline and the internal standard theobromine using penta-fluorobenzyl bromide, in connection with an electron capture detector. To 100 ul samples of plasma containing 50-1000 ng theophylline, 100 yl of a solution of the internal standard were added. The extraction was performed by column extraction (cellulose) using dichloro-methane as solvent. After back extraction into an alkaline aqueous phase (NaOH), theophylline and theobromine were alkylated with pentafluorobenzyl bromide by an extractive alkylation technique. The derivatives were extracted with cyclohexane and, after concentration to 3 ml, 2 yl were injected for the gas chromatographic assay. Standard deviation of the method was 2.5 % at a concentration level of 200 ng per sample, and 8 % at 20 ng per sample. The sample amounts were 100 yl plasma and 250 mg rat brain tissue, and the sensitivity limit... 

Johanson G. 1989. Analysis of ethylene glycol ether metabolites in urine by extractive alkylation and electron-capture gas chromatography. Arch Toxicol 63 107-111. 

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