Alcohols derivatization

Oxidation of Derivatized Alcohols - Derivatized Aldehyde Formation... 

A useful modification of the Barton deoxygenation of secondary alcohols involves the use of O-phenylthionocarbonates developed by Robins et al. [15]. Application of this method for the generation and cyclization of a hex-5-ynyI radical is shown is Scheme 5. The precursors are readily prepared from D-ribose by a Grignard addition, followed by selective alcohol derivatizations. The major exo-isomer has been converted into carba-a-D-ribofuranose [16]. 

Rational application of the chemical transformation method also improves the speed of determination. Fig. 10 [30] shows chromatograms of alcohols derivatized to fluoro-propionates (A) and propionates (B) free alcohols cannot be eluted under these conditions. These chromatograms demonstrate that, the selection of a volatile derivative (pentafluoropropionate) substantially reduces the separation time. 

In situ" derivatization of water soluble epoxy-alcohol... 

The advantage of this ketal is that unlike the THP group, only a single isomer is produced in the derivatization. Conditions used to hydrolyze the THP group can be used to hydrolyze this acetal. This group may also find applications in the resolution of racemic alcohols. 

A large number of silylating agents exist for the introduction of the trimethylsilyl group onto a variety of alcohols. In general, the sterically least hindered alcohols are the most readily silylated, but these are also the most labile to hydrolysis with either acid or base. Trimethylsilylation is used extensively for derivatization of... 

Pentafluorobenzyl bromide has been used in the derivatization of mercaptans [55] and phenols [36], m the analysis of prostaglandins [37], and in quantitative GC-MS [5S] 1,3 Dichlorotetrafluoroacetone is used for the derivatization of amino acids to the corresponding cyclic oxazolidinones and allows the rapid analysis of all 20 protein ammo acids [d] Pentafluorophenyldialkylchlorosilane derivatives have facilitated the gas chromatographic analysis of a wide range of functionally substituted organic compounds, including steroids, alcohols, phenols, amines, carboxylic acids, and chlorohydrms [4]... 

Epoxidation of the simplest allylic alcohol, allyl alcohol 7, is achieved in 88-92% ee with yields of 50-60% using diisopropyl tartrate as ligand. In situ derivatization of the product glycidol 8 via esterification, sulfonylation, or ring opening with nucleophile is an attractive alternative to isolating glycidol. 

In general, 2-substituted allylic alcohols are epoxidized in good enantioselectivity. Like glycidol, however, the product epoxides are susceptible to ring opening via nucleophilic attack at the C-3 position. Results of the AE reaction on 2-methyl-2-propene-l-ol followed by derivatization of the resulting epoxy alcohol are shown in Table 1.6.1. Other examples are shown below. 

Sanofi-Synthelabo researchers discovered pyrazole 53 and analogs to have potent Cannabinoid receptor-1 (CB-1) antagonist/inverse agonist activity and have progressed 53 into development for treatment of obesity and alcohol dependence. The synthesis of 53 was accomplished by heating the diketone sodium salt 51 with the aryl hydrazine hydrochloride in acetic acid to provide the intermediate 52, which was further derivatized... 

The most important group of derivatives for the amino function (Fig. 7-4) is the carbamate group, which can be formed by reactions with acids, acid chlorides or acid anhydrides. A series of chlorides as 2-chloroisovalerylchloride [1], chrysanthe-moylchloride [2] and especially chloride compounds of terpene derivatives (cam-phanic acid chloride [3], camphor-10-sulfonyl chloride [4]) are used. The a-methoxy-a-trifluoromethylphenylacetic acid or the corresponding acid chloride introduced by Mosher in the 1970s are very useful reagents for the derivatization of amines and alcohols [5]. 

Most of the reactions applied to amines can also be transferred to alcohols (Eig. 7-5). One large group of chiral alcohols are the (i-adrenoreceptor blockers, for which a variety of derivatization agents was developed. One highly versatile reagent for the separation of (i-blockers is A-[(2-isothiocyanato)cyclohexyl]3,5-dinitrobenzoyl-amide (DDITC) [11]. Alternatively, unichiral drugs such as (3-blockers or (S)-naproxen [12] may be used in a reciprocal approach to derivatize racemic amine compounds. 

Methyl-substituted primary alcohols can be separated after derivatization with [6-methoxy-2,5,7,8-tetramethylchromane-2-carboxylic acid] (Trolox M methyl ether) [13] while sec.- and tert.-alcohols are derivatized with 2-dimethylamino-l,3-dimethyl-octahydro-lf/-l,3,2-benzodiazaphosphole [14] (Eig. 7-5). 

Fig. 7-6). Two unichiral amides which have been known capable of this reaction are 1-phenylethylamine [15] and l-(l-naphthyl)ethylamine [16]. Marfey s reagent [N-a-(2,4-dinitro-5-fluorophenyl)-L-alaninamide] was introduced as a reagent to deriva-tize amino acids with cyclopentane, tetrahydroisoquinoline or tetraline structures [17]. Simple chiral alcohols such as 2-octanol can also be used to derivatize acids such as 2-chloro-3-phenylmethoxypropionic acid [18]. 

An example for this approach is the immobilization of (5 )-(-)-a-A-(2-naph-thyl)leucine, a 7t-donating group on silica. This chiral selector exhibits excellent recognition for 3,5-dinitrobenzoyl (DNB)- and 3,5-dintroanilido (DNAn)-deriva-tives. Amines and alcohols can be derivatized with DNB- or DNAn-chloride to the esters or carbamates and separated on the CSP, as shown by Pirkle for a wide variety of compounds [27]. 

In analytical LC there are two primary reasons why chemical derivatization of the sample constituents would be necessary, and they are 1) to enhance the separation and 2) to increase the sensitivity of detection. Under certain circumstances, derivatization can also be used to reduce peak asymmetry, i.e. to reduce tailing, or to improve the stability of labile components so that they do not re-arrange or decompose during the chromatographic process. However, sensitivity enhancement is the most common goal of derivatization. For example, aliphatic alcohols that contain no UV chromaphore can be reacted with benzoyl chloride to form a benzoic ester. 

Reports on the use of fluorescent derivatives abound (5). Some reagents have become widely used. The dansyl group is probably the most thoroughly studied. Dansyl chloride has been widely used as a fluorescent derivatizing reagent for HPLC (6,7). It reacts readily with primary and secondary amino groups (7) and with phenols (8), but forms derivatives of alcohols very slowly (9). The lower detection limit for dansyl derivatives of aliphatic amines is in the range of 300 femtomoles per injection. 

In Situ Derivatization. To demonstrate that a group of alcohols could be derivatized at low alcohol concentration, the following experiment was performed. First, 6 x 10 mole of each of the alcohols used to form derivatives was dissolved in 100 ml of acetonitrile. Then 2 x 10" mole of compound V was added, and the solution was heated at 70°C. This solution was then diluted by taking 1.0 mL of the reaction mixture and diluting to 10 mL with water and acetonitrile, and the diluted solution was analyzed. After 4 h the methanol and ethanol were completely derivatized, but it took 6 h for the n-propanol and n-butanol derivatives to form. 

Synthesis of Derivatizing Reagent III. We placed 50 mL of methanol, which had been previously dried over 4-S molecular sieves, in a 100-mL round-bottom flask and added 6.0 g of 2-hydroxynicotinic acid and 3 mL of boron trifluoride etherate. The solution was heated to reflux for 24 h and the solvent was removed under reduced pressure. The residue was dissolved in 50 mL of 0.1-ff sodium hydroxide and extracted with 60 mL of chloroform. The chloroform extract was concentrated under reduced pressure and the residue crystallized from isopropyl alcohol. The yield of 3-carbomethoxy-2(lH)pyridone was 5.0 g mp 152.5-154°C NMR (CDCI3) 6 3.85 (s, 3, -CH3), 6.34 (t, 1,... 

Note The derivatized steroids can be extracted from the blue chromatogram zones with alcohol and quantitatively determined by means of the Zimmermann reaction, which is not interfered with by the presence of phosphoric acid and phosphomolybdic acid. A yellow background can be bleached by exposure to anunonia vapor [2]. 

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