Fluoride derivatization

The most general method for the simultaneous analysis of oxyanions by gas chromatography is the formation of trimethylsilyl derivatives. Trimethylsilyl derivatives of silicate, carbonate, oxalate, borate, phosphite, phosphate, orthophosphate, arsenite, arsenate, sulfate and vanadate, usually as their ammonium salts, are readily prepared by reaction with BSTFA-TMCS (99 1). Fluoride can be derivatized in aqueous solution with triethylchlorosilane and the triethylfluorosilane formed extracted into an immiscible organic solvent for analysis by gas chromatography [685). 

Potentially tautomeric pyrimidines and purines are /V-alkylated under two-phase conditions, using tetra-n-butylammonium bromide or Aliquat as the catalyst [75-77], Alkylation of, for example, uracil, thiamine, and cytosine yield the 1-mono-and 1,3-dialkylated derivatives [77-81]. Theobromine and other xanthines are alkylated at N1 and/or at N3, but adenine is preferentially alkylated at N9 (70-80%), with smaller amounts of the N3-alkylated derivative (20-25%), under the basic two-phase conditions [76]. These observations should be compared with the preferential alkylation at N3 under neutral conditions. The procedure is of importance in the derivatization of nucleic acids and it has been developed for the /V-alkylation of nucleosides and nucleotides using haloalkanes or trialkyl phosphates in the presence of tetra-n-butylammonium fluoride [80], Under analogous conditions, pyrimidine nucleosides are O-acylated [79]. The catalysed alkylation reactions have been extended to the glycosidation of pyrrolo[2,3-r/]pyrimidines, pyrrolo[3,2-c]pyridines, and pyrazolo[3,4-r/]pyrimidines (e.g. Scheme 5.20) [e.g. 82-88] as a route to potentially biologically active azapurine analogues. 

This isomerization was confirmed by means of a detailed kinetic NMR study (90T633), but is not detrimental to the synthesis of substituted 1,2,4-triazoles, because in all cases removal of the protecting group leads to a tautomeric mixture of 3- and 5-substituted products. The methods available for removal of the animal function actually depend upon the nature of the added C-5 substituent, with acid hydrolysis occurring only in some cases. More commonly, treatment with NaBH in refluxing ethanol is the method of choice (90T633). Lithiation and derivatization of the SEM protected compound (entry 6) can be achieved without the isomerization shown by the animal derivative, and deprotection can be achieved with either aqueous acid or anhydrous fluoride ion [92H(34)303], However, overall reaction yields are not as high as those for the aminal system. 

After capping (i.e. acetylation of the remaining hydroxyl groups), the resulting functionalized cellulose can be used for the synthesis of peptides using both the Boc and Fmoc methodologies. Because cellulose is hydrolyzed by hydrogen fluoride (but not by TFA), nucleophilic saponification must be used to cleave the peptides from the support [209]. Alternatively, the support can be derivatized with a TFA-labile linker [211]. 

The 2.2.2 column is especially advantageous in the determination of fluoride ion, which in traditional IC often elutes so early as to be masked by the injection peak. [32] In similar fashion, Tsai and Shih [33] derivatized polystyrene/divinylbenzene resin with cryptand 2.2.2 for the ion chromatographic separation of cations or anions. 

In the actual synthesis, aldol reaction 1 involved a lithium enolate whilst aldol reactions 2-4 used boron enolates based on the mandelic acid derivatives described above to incorporate fragments A, B, and C. The aldol products of reactions 2 1 were treated with fluoride and then NaIC>4 to release carboxylic acids which were derivatized or reduced as appropriate. 

The spot synthesis technique is simple and easily accessible for practical use. There are some limitations to the scope of chemistries that can be used with cellulose as a solid support. To eliminate some of these shortcomings, Gao and EsnoufP° 4 proposed using a different membrane, Immobilon AV-1, for spot synthesis. Before the synthesis of peptide arrays can be carried out, this polyvinylidene fluoride based material is derivatized with ethane-1,2-diamine, followed by coupling of Fmoc-(3Ala as a spacer. In most other aspects, this peptide array synthesis is very similar to the spot synthesis proposed by Frank.t l... 

It was assumed that an a-fluorosilyl potassium species was formed initially, and that this subsequently underwent a self-condensation reaction. The eventual product (1) displayed both nucleophilic as well as electrophilic character, which was demonstrated in various derivatization reactions. Although it contains fluorine and potassium atoms in close proximity, the compound displayed a remarkable thermal stability. Even at 80 °C, potassium fluoride elimination occurred only sluggishly. Attempted transmetalation reactions with various metal halides, though, caused an immediate elimination of metal fluoride and the formation of tetrakis(trimethylsilyl)disilene. The latter can be trapped in cycloaddition reactions [5] or, in the absence of trapping reagents, it dimerizes to a cyclotetrasilane (Scheme 2) [6]. 

Hydroxyl protection. Derivatization of alcohols into the sisyl ethers using DMAP as base at room temperature furnishes their protection. These silyl ethers are resistant to fluoride ion but can be removed on photolysis in methanol. 

The first application of copper(I)-catalyzed 1,3-dipolar cycloaddition in preparation of [18F]fluoropeptides was reported by Marik and Sutcliffe in 2006 (Figure 14.9) [92]. Three [18F]fluoroalkynes (n = 1, 2, and 3) were prepared in yields ranging from 36% to 80% by nucleophilic substitution of a p-toluenesulfonyl moiety with [18F]fluoride ion. Reaction of these [18F]fluoroalkynes with various peptides (previously derivatized with 3-azidopropionic acid) via the Cu(I)-mediated 1,3-dipolar cycloaddition provided the desired 18F-labeled peptides in 10 minutes at room temperature with yields of 54-99% and great radiochemical purity (81-99%) [82]. 

On column benzylation of phenols was carried out with 3,5-bis(trifluoromethyl)benzyl-dimethylphenylammonium fluoride (54). Fluorinated benzyl derivatives allow very sensitive detection of phenols at ppt levels, by GC-MS in the negative ion chemical ionization mode. Derivatizing with pentafluorobenzyl bromide (C6F5CH2Br) was proposed for GC-MS detection of airborne carboxylic acids and phenols" . 

To take advantage of l9F NMR, carbonyl groups including quinones have been derivatized by reaction with trifluoromethyltrimethyl-silane in the presence of tetramethylammonium fluoride followed by hydrolysis of the trimethylsilyl ethers (Ahvasi et al. 1999). The method was applied to analysis of the various carbonyl groups in lignin. 

Fluoride can be derivatized in aqueous solution and extracted by trimethyl-chlorosilane into an immiscible organic solvent. 

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