Patai S., Rappoport Z. 1996 The chemistry of functional groups. The chemistry of amino, nitroso, nitro and related groups. Part 2 / 1041 1168

(S)-1,10-Binaphthyl-2,20-diol (191) was proposed as a chemical shift reagent for assessing the chiral purity of amino alcohols. It gave a split of about 0.3 ppm for the N CH3 signal of the enantiomer of compound 192 and smaller splits for other configurations399.

PhNHCO2 CHCONHBu

(S)-N-n-Butyl-2-(phenylcarbamoyloxy)propionamide (193) was used as chiral solvating agent in the NMR determination of the enantiomer composition of the N-(3,4- dinitrobenzoyl) derivative of amino acid ethyl esters400.

A general approach for the determination of the absolute configuration of a chiral carbon consists of attaching to it a labile chiral unit and a dissymmetric chromophore and measuring the optical rotation at the sodium D line. This has been successfully applied to amino acids401.

Some synthetic polypeptides form lyotropic cholesteric liquid crystals when dissolved in organic solvents. That is the case of poly( -benzyl L-glutamate) in methylene dichloride. This system can be used as a chiral solvent to distinguish enantiomers by 2H NMR. In such chiral solvents the averaged ordering parameters are different for each enantiomer. The quadrupolar splitting of CD3 signals, Q, is very sensitive to this differential ordering. Determination of enantiomer excess of amino acids requires the scheme shown in reaction 34: The amino acid is esterified with deuterated methanol in the presence of thionyl chloride; the acidity of the reaction mixture is removed with propylene oxide yielding the ˛-amino ester 193 that, in principle, can be dissolved in the liquid crystal submitted to 2H NMR analysis. However, these esters tend to dimerize and yield the corresponding 2,5-diketopiperazines (194). Hence a Schiff base (195) is produced by treatment of 193 with benzophenoneimine and used for dissolution in the liquid crystal402.

O

H

R N O

CO2 CD3

2-Amino-5-chlorobenzophenone, an impurity of chlordiazepoxide, can be determined by spectrofluorometry after oxidative cyclization (reaction 35). Chlordiazepoxide does not react403.

(35)

An NMR study on the conformation of glucopyranosylammonium compounds showed that the general tendendency of many electronegative substituents at C 1 to adopt an axial conformation was prevalent in this case too, as depicted in equilibrium 36 for R groups of various sizes. These results disclaim the importance of the so-called ‘reverse anomeric effect’404.

TABLE 4. Examples of environmental, occupational and quality control protocols for industrial quaternary ammonium compounds

a Nomenclature may vary from source to source. See also Reference 69. b Entry number in Reference 70.

c Codes beginning with I and N denote FTIR spectra in Reference 71 and NMR spectra in Reference 72, respectively. d A code of two letters followed by seven digits is a reference to RTECS of NIOSH/OSHA. Standard samples are commercially available for compounds with reference to USP protocols74.

e The compound has two or more quaternary ammonium groups of the same type.

f The compound has several types of quaternary ammonium and amino functional group. g A pesticide, see Reference 75.

1116 Jacob Zabicky and Shmuel Bittner

A. Chromatography

A method for extraction, purification and preconcentration of dialkyldimethylammonium compounds and other detergents before determining their concentration in sewage water and activated sludge was described. It consists of a series of LLE and LC operations, the details of which are dependent of the original matrix, and end analysis was by HPLC-ELCD406.

A general approach to the analysis of aqueous solutions of quaternary ammonium compounds containing large alkyl groups consists of extracting with an organic solvent, applying a separation method and determining the specific components with an adequate sensor. Sometimes an anionic reagent, for example a chromophore, is added to the aqueous medium and the ammonium cation becomes paired to it in the extraction. This approach was used for the determination of quaternary ammonium compounds present in milk, after extraction by the Mojonnier method for fat in milk, RP-LC and detection with diode array at 217 280 nm407. An interlaboratory study was carried out for the determination of di(hardened tallow)dimethylammonium surfactants in sludges, sediments, soil and aqueous environmental samples, down to ppb concentrations. The method consisted of HPLC-ELCD; LOD in environmental liquids and solids 2.5 mg/L and 0.5 mg/g, respectively, intralaboratory RSD 7% and recovery 90%. The method is highly specific as opposed to the nonspecific colorimetric one based on ion pairing to disulfine blue (198). The method can be extended to other surfactants408. The various homologues of benzalkonium chloride (197b) in ophthalmic and nasal preparations can be determined by RP-HPLC on a C8 column and UVD with a diode array, measuring at 260 nm409. The HPLC-UVD procedure is quite simple and adequate for such preparations, and does not suffer from common interferences; recovery of 100.2 š 1.2% n D 10 410 412. A fast FIA-based spectrophotometric method was proposed for determination of benzalkonium chloride (197b) and N-cetylpyridinium chloride, consisting of ion-pair extraction and association of the cations with the anion of tetrabromophenolphthalein ethyl ester (199). The interference caused by ordinary amines on association with 199 disappears on heating to 45 °C, when the color of these associates fades away413. The associates of 199 with berberine (200) and benzethonium (201) at pH 11 have a blue color. This was applied to the determination of these quaternary bases, measuring at 610 nm, batchwise or in an FIA system414. A screening method for the presence of ditallowdimethylammonium ions in environmental waters consists of SPE, normal HPLC and post-column pairing with the fluorescent anion 9,10-dimethoxyanthracene-2-sulfonate (202) ( ex 384 nm, fl 452 nm); LOQ 5 mg/L with 21 š 3% recovery415. A special FIA system was designed for determination of quaternary ammonium compounds, in which segments of solution containing the quaternary ammonium cation paired with a chromophoric anion are alternated with a segment of insoluble solvent. The ion pair becomes adsorbed and preconcentrated on a part of the conduit loaded with immobilized adsorbent, and it is subsequently desorbed by extraction with the organic solvent and measured in a suitable detector. LOD < 10 7 M for tetrabutyl ammonium paired with bromothymol blue (203)416.

Samples containing quaternary ammonium compounds with a wide range of molecular weights gave unsatisfactory results by HPLC coupled with various detectors (RID, ELCD, UVD). In such cases evaporative light scattering (ELS) may be of advantage. This consists of nebulizing the effluent of the LC column, drying the solvent and carrying the cloud of fine solid particles past a light source. The light scattered by the cloud is detected with a photomultiplier. The method was applied for determination of low levels of alkyltrimethylammonium and methyltrialkylammonium in dialkyldimethylammonium products, using a bonded polyphenol silica gel column with gradient elution417.

A fast and accurate screening test was proposed for nine quaternary ammonium drugs in urine, including pancuronium (206), ambenonium (211), benzethonium (201), neostigmine (212) and propantheline (213). The drugs were extracted as the triodide (I3 ) into dichloromethane and analyzed by direct inlet EI-MS; LOD was 20 150 mg/L for all the analytes428. Analysis of the neuromuscular blocking agents pancuronium bromide (206) and vecuronium bromide (214) in plasma or urine was performed by CI-MS, placing samples of an extract on the moving belt and monitoring the single metastable transition corresponding to elimination of acetic acid from the m/z 543 ion. The method is sensitive to concentrations below 5 mg/L429.

The induced circular dichroism and Cotton effect have been investigated for quaternary ammonium ions with N anchored on an asymmetric C, when hosted in calix[n]arene molecules (215, n D 4, 6, 8)430.