Primary and Secondary Hydroxyl Groups

The amount of primary and secondary hydroxyl groups present in polyols may be of interest in polyurethanes, since they may influence reaction rates and physical properties of the finished polymer. 

The use of differential reaction rates to analyze mixtures of alcohols for the primary and secondary hydroxyl contents is possible based on the differences in reaction rate of different alcohols with acetic anhydride. A linear plot for second-order reactions makes possible the analysis of mixtures containing the same functional group. The integrated form of the equation describing second-order reactions is 

A sample containing approximately 0-5 mol of hydroxyl is acetylated with acetic anhydride in pyridine, and aliquots are removed at known time intervals, hydrolyzed and back-titrated with standardized NaOH. A blank is treated similarly and log[(i—x )/(a —x )] plotted versus t. 

An infrared method for the analysis of primary alcohols in polyglycols based on the reaction of the polyol with triphenylchloromethane is where the reagent consists of trityl chloride, with tris(dimethyl amino)phosphine oxide in quinoline as a solvent. This reagent is added to the sample, scanned from 3700 to 3100 cm to establish the total hydroxyl absorbance, and the reaction is then carried out in a glass-stoppered flask in a thermostatted bath at 75°C. At appropriate times, aliquots are removed and scanned, the absorbance being measured at 3280cm 

A rate plot is made and extrapolated back to zero time. The rate of disappearance of the secondary hydroxyl band is measured, and the quantity of primary alcohol is determined by difference. The method is based on the fact that the reaction rate of triphenylchloromethane with primary alcohols is 25-100 times faster than the reaction rate with secondary alcohols. 

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Most carbohydrates have two kinds of reactive groups the carbonyl group and primary and secondary hydroxyl groups. 

Some of the original work in the carbohydrate area in particular reveals extensive protection of carbonyl and hydroxyl groups. For example, a cyclic diacetonide of glucose was selectively cleaved to the monoacetonide. A summary describes the selective protection of primary and secondary hydroxyl groups in a synthesis of gentiobiose, carried out in the 1870s, as triphenylmethyl ethers. 

Silylation of both the primary and secondary hydroxyl groups is followed by selective deprotection to regenerate the primary hydroxyl group. 

Thanks to the difference of reactivity between primary and secondary hydroxyl groups, mono and ditelomers corresponded only to the reactivity of the terminal alcohols (Fig. 3). 

The difference in reactivity of primary and secondary sulfonyloxy groups towards replacement by iodine was originally the basis of a method for distinguishing between primary and secondary hydroxyl groups in cyclic sugar molecules [see, J. W. H. Oldham and J. K. Rutherford,/. Amer. Chem. Soc., 54, 366 (1932)]. 

Dihydro-2f/-pyran (167) is well known in organic chemistry as a reagent employed for the temporary protection of primary and secondary hydroxyl groups. Addition reactions to the double bond of 167 afford compounds that fall into the category of 3,4-dideoxypentoses. 

Carbonylazides can also be used for fluorescent labeling of both primary and secondary hydroxyl groups. Including in this class of reagents are 7-me-thoxycoumarin-3-carbonylazide and 7-methoxycoumarin-4-carbonylazide (181). 

A. Hasegawa, T. Nagahama, H. Ohki, K. Hotta, H. Ishida, and M. Kiso, Reactivity of glycosyl promoters in a-glycosylation of W-acetylneuraminic acid with the primary and secondary hydroxyl groups in the suitably protected galactose and lactose derivatives, J. Carbohydr. Chem. 70 493 (1991). 

A (1—>5)-linkage for the polyribose is expected to be a preponderant linkage, based on the relative reactivities of primary and secondary hydroxyl groups 2 and on the tendency 1 of D-ribose to adopt the furanose form. However, the anomeric configuration of the polyribose is, most probably, a mixture of a-D and /3-d linkages, since a mixture of D-ribose and adenine, under the influence of polyphosphoric acid esters,w gave, among other products, approximately equal proportions of adenosine and its a-D isomer. 2... 

Acetone-soluble cellulose acetate is prepared by deacetylating cellulose triacetate. The product formed directly is unsatisfactory. Thus the distribution of free hydroxyls and acetate groupings is of primary importance. Cramer and Purves118(b) studied the distribution by tosylation and found that the acetyl removal from primary and secondary hydroxyl groups occurs at approximately the same rate, but that the number of... 

Both primary and secondary hydroxyl groups react rapidly [389, 408-412] under classical Corey conditions [388] with rm-butylchlorodimethylsilane in DMF in the presence of imidazole catalyst. The primary hydroxyl group reacts preferentially, the ratio of products being dependent on the amount of imidazole present. For thymidine, the highest, ca. 75% yield of 5 -ether has been obtained [389,408] with a ratio of nucleoside /ert-butylchlorodimethylsilane imidazole near 1 1.1 2.2. Similar results were obtained with other deoxyribonucleosides [389, 408], as well as with uridine [410,411, 413], adenosine [410,411], cytidine [414], guanosine [414], and their... 

Besides the special reactivity of the OH-2, OH-1, and OH-3 groups lies also the classical relative reactivity between the primary and secondary hydroxyl groups. Depending on the reaction conditions and the nature of the electrophilic species, it may be seen that these two types of possible reactivity can direct the reactivity of sucrose. Of course, the product distribution also depends on whether the transformations are kinetically or thermodynamically controlled. For those reactions under kinetic control, if there is enough difference in the rate of the first substitution at the most reactive hydroxyl group and the second one, then the regioselectivity also monitors the degree of substitution. 

Glycosylation.1 When treated with 1, RS- or ArS-glycosides undergo glycosy-lation with primary and secondary hydroxyl groups of O-glycosides to give P-O-linked disaccarides. Acetonitrile is the only suitable solvent. 

Cellulose Esters. Cellulose contains primary and secondary hydroxyl groups. Hence, cellulose esters can be made with all inorganic and organic acids. Traditionally, cellulose esters are made by a controlled acid-catalyzed reaction between an acid or acid anhydride and the hydroxyl groups of cellulose. The reaction requires the absence of water for completion because it is a reversible reaction. The general reaction scheme can be illustrated as shown in Scheme 1. 

Alcohol protection. Primary and secondary hydroxyl groups are esterified by 1 in the presence of pyridine (71-92% yield). The usual selectivity for acylation of primary versus secondary hydroxyl functions obtains. The resulting 2-di-bromomethylbenzoates 2 are deprotected under neutral conditions by silver perchlorate mediated hydrolysis to 2-formylbenzoate esters 3 (2,6-lutidine or 2,4,6-collidine is added to maintain a virtually neutral reaction medium). Addition of morpholine then leads to rapid dcacylation with release of the alcohol in high yield... 

ROH— RI The combination of triphenylphosphine and 2,4,5-tri-iodoimidazole in toluene at elevated temperature (120°) effects replacement of primary and secondary hydroxyl groups of carbohydrates by iodine with inversion of configuration. The reaction is heterogeneous and the carbohydrate need not be soluble in toluene. Triphenylphosphine, iodine, and imidazole can also be used, but the yields are generally lower. 

Benzyl ethers are not cleaved by 1. Removal of the benzyl ether function can, however, be achieved with the cation radicals of amines 2 or 3. Thus selective deprotection of primary and secondary hydroxyl groups is possible. These deprotections can be performed in the presence of primary or secondary alkyl bromides, which are unaffected by 1 or the radical cations of 2 or 3. 

Hanna and Siggia described the application of simultaneous analysis techniques to systems such as those containing primary and secondary hydroxyl groups, mixtures of amides and nitriles, and sugars and amino acids. 

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