Derivatization of aldehydes and ketones

Aldehydes and ketones containing a hydrogen atoms exist in tautomeric equilibrium with the corresponding enols 

If hydroxylamine rather than methoxyamine is used, the result is an oxime, a less satisfactory compound, because it contains a polar hydroxyl group (R2CO + NHjOH - R2C=N0H) silylation of the hydroxyl groups of the substrate, however, also causes silylation of the oxime hydroxyl group, creating a satisfactory derivative. 

Oximes may also be converted by an exchange reaction into methoximes and higher alkyloximes. It was shown [229], in a study involving a number of steroids, that the rate of displacement of the hydroxyl group of an oxime by a methoxyl 

For electron-capture detection, pentafluorobenzyloxyamine has been described [230]. 2-Chloroethoxyamine [231] has been recommended as an oximating agent of high reactivity, yielding chlorooximes the chloro-compound mass-spectral pattern is alleged to be helpful in identification. 

Advantage is taken of the reactivity of a-dicarbonyl compounds toward aromatic 

---

Methods for derivatization of aldehydes and ketones using preformed Mannich reagents have been summarized.2-(Morpholinothio)benzothiazole (55) is a key reagent in a synthesis of 2-substituted cyclopentenones from the cyclo-pentanone (Scheme 47). 

If a soluble reagent containing an ultraviolet (UV)-active group or dye can be used, then it may be possible to estimate the reaction yield from the amount of unreacted reagent stiU remaining in the supernatant solution at the end of the reaction. For example, the derivatization of aldehydes and ahphatic ketones with dansylhydrazine has been monitored by fluorescence spectroscopy of the supernatant solution, and has been used to quantify the amount of supported aldehyde or ketone. 

Used for the precolumn preparation of fluorescent derivatives of aldehydes and ketones optimal derivatization of glucose and other sugars occurs at pH 2-3 Reference 11... 

Olson KE, Swarin SJ. 1985. Determination of aldehydes and ketones by derivatization and liquid chromatography-mass spectrometry. J Chromatogr 333 337-347. 

M2. Mann, B., and Greyeski, M. L., New chemiluminescent derivatizing agent for the analysis of aldehydes and ketones by high performance liquid chromatography with peroxyoxalate chemiluminescence. 7. Chromatog. 386, 149-158 (1987). 

D. W. Johnson, A modified Girard derivatizing reagent for universal profiling and trace analysis of aldehydes and ketones by electrospray ionization tandem mass spectrometry. Rapid. Commun. Mass. Spectrom., 21 (2007) 2926-2932. 

The hydrazone derivatives, oximes, and semicarbazones discussed in this section are rather specialized compounds. Why mention them Organic chemists rely on spectroscopy (see Chapter 14) to identify the structure of organic compounds, but prior to the development of spectroscopy, chemical reactions were used as an identification tool. One such method converts unknown organic compounds to solid derivatives. The color and melting point of several derivatives are cross-referenced to a library of known derivatives to help identify the unknown. The conversion of aldehydes and ketones to phenylhydrazones, 2,4-dinitrophenylhydrazones, oximes, and semicarbazones is one method used for derivatization. 

The production of optically active cyanohydrins, with nitrile and alcohol functional groups that can each be readily derivatized, is an increasingly significant organic synthesis method. Hydroxynitrile lyase (HNL) enzymes have been shown to be very effective biocatalysts for the formation of these compounds from a variety of aldehyde and aliphatic ketone starting materials.Recent work has also expanded the application of HNLs to the asymmetric production of cyanohydrins from aromatic ketones. In particular, commercially available preparations of these enzymes have been utilized for high ee (5)-cyanohydrin synthesis from phenylacetones with a variety of different aromatic substitutions (Figure 8.1). 

Peters R, Hellenbrand J, Mengerink Y, Wal Van der S. 2004. On-line determination of carboxylic acids, aldehydes and ketones by high-performance liquid chromatography-diode array detection-atmospheric pressure chemical ionization mass spectrometry after derivatization with 2-nitrophenylhydrazine. J Chromatogr A 1031 35. 

Results from the two experiments conducted on the aldehydes and ketones are listed in Table III as separate sets of data to illustrate the care that must be exercised in conducting and evaluating these runs. Both C02 extractions were performed under similar conditions. However, in the second run, the U-tube traps were contacted with the 2,4-dinitrophenylhydrazine derivatizing solution for longer periods of time. This modification in the analytical procedure permitted higher total mass accountabilities in the second experiment, ranging from 64.9% for isophorone to 28.7% for methyl isobutyl ketone. The recoveries from the raffinate for each of these compounds remained relatively constant. This result suggested that the trap recoveries in the first case were artificially low. 

Derivatization is a procedure in which analyte is chemically modified to make it easier to detect or separate. For example, formaldehyde and other aldehydes and ketones in air, breath, or cigarette smoke25 can be trapped and derivatized by passing air through a tiny cartridge containing 0.35 g of silica coated with 0.3 wt% 2,4-dinitrophenylhydrazine. Carbonyls are converted into the 2,4-dinitrophenylhydrazone derivative, which is eluted with 5 mL of acetonitrile and analyzed by HPLC. The products are readily detected by their strong ultraviolet absorbance near 360 nm. 

Aldehydes and ketones are readily oxidized and must, therefore, be deriva-tized and extracted within 48 h of sample collection. The derivatized sample extracts should be analyzed within 3 days after preparation. Holding times exceeding more than 3 days have shown significant losses of compounds having seven or more C atoms. Samples should be collected without headspace and should be... 

The low volatility of amino acids renders the GC of free acids impossible. A-trifluoroacetyl-n-butylesters proved to be most suitable and preparation is quite easy. Aldehydes and ketones can be converted to oximes, enamines, etc. New derivatization reactions are pubhshed every year... 

Review of compounds used to derivatize aldehydes and ketones in tobacco smoke. 

There are many HPLC methods for the determination of aldehydes in ambient air. They differ in sampling technique, elution and chromatographic separation (Tuss et al., 1982). 2.4-Dinitrophenylhydrazine DNPH (LIS, 1989 VDI 3862, Part 2, 1990 Selim, 1977 Druzik et al., 1990 Lipari and Swarin, 1982 Slemr, 1991) is now widely used for derivatization because this reagent is also suitable for the simultaneous analysis of long-chain aldehydes, aromatic aldehydes and ketones. In acidic solution, DNP-hydra-zone derivatives are formed from DNPH and aldehydes or ketones as shown in Eq. (6). The reaction proceeds with nucleophilic addition to the carbonyl group followed by elimination of water. 

Derivatization of drugs containing a carbonyl function aldehydes and ketones... 

Some special methods for derivatization of simple low boiling aldehydes and ketones are used for the displacement of their analytical signals into less populated parts of chromatograms. It increases the resulting selectivity for determining target analytes. 

---