Cellulose carbamate derivatives

Cellulose reacts with isocyanates in anhydrous pyridine or with urea and substituted ureas at relatively high temperature to yield carbamates. The optimum carbamation reaction of microcrystalline cellulose with urea in a dry solid mixture has been studied [51]. In addition, a preferentially C6-modified cellulose carbamate derivative has been obtained [52]. Heating of cellulose with thiourea at 180°C yielded cellulose thiocarbamate [53]. Heat treatment of cellulose isocyanate products has been utilized for the production of urethanes [54]. When ceUuIose was treated with phenylisocyanate at 100 C in DMF in the presence of dibutyltin dilaurate and triethylenediamine, celiuiose bisphenylcarbamate was formed [55]. Treatment of cellulose with urea at temperatures at or above the latter s melting point (where urea decomposes into isocyanic acid and ammonia) has been employed for the production of cellulose carbamates fibers [56]. The advantages and disadvantages of using urea as an intermediate for production of fiber have been discussed [57]. 

To address development of chiral separations by SFC, Villeneuve and Anderegg have developed an SFC system using automated modifier and column selection valves. Columns (250 x 4.6 mm i.d., 10 pm) packed with Chiralpak AD, Chiralpak AS amylose derivative, Chiralcel OD cellulose carbamate derivative, and Chiralcel OJ cellulose ester derivative (Chiral Techologies, Exton, PA) were connected to a column-switching valve. Candidate samples were run successively on each column using fixed isocratic, isobaric, and isothermal conditions of 2 ml/min, 205 atm pressure, and 40 °C with the vari-... 

The Finnish viscose producer Kemira Oy Saeteri collaborated with Neste Oy on the development of a carbamate derivative route. This system is based on work (89) that showed that the reaction between cellulose and urea gives a derivative easily dissolved in dilute sodium hydroxide ... 

In this context, the enantiomeric pair containing the eutomer of cyclothiazide can be resolved by HPLC on cellulose-derived coated CSPs. Nevertheless, the poor solubility of this compound in solvents compatible with this type of support makes this separation difficult at preparative scale. This operation was achieved with a cellulose carbamate fixed on allylsilica gel using a mixture of toluene/acetone as a mobile phase [59]. 

Carbamate derivatives (Table 1) of cellulose, chitin, amylose, amylopectin, and dextran were prepared using the isocyanates described in Part A of the Experimental Section. Amylose, amylopectin, dextran, and cellulose were obtained from Polysciences, Inc. and used without further purification. Chitin, obtained from Eastman Kodak, was decalcified and deproteinated by the method reported by Haye r prior to use. 

Preweighed 1.0 mg samples of each polysaccharide carbamate derivative were submerged in aqueous solutions at three pH values 3.1 7.0 and 11.3. Three milliliter aliquots were withdrawn at periodic intervals and analyzed by ultraviolet spectroscopy. Typical results are shown in Figures 3 and 4 for pendant hydrolysis rates of carbamate derivatives of cellulose and chitin respectively as a function of pH. 

Figures 3 and 4 illustrate typical rates of hydrolysis for carbamate derivatives of cellulose and chitin. The rates of release at a pH value 11.3 were considerably higher in both systems than at pH values of 3.1 and 7.0. After seven days in the basic medium the cellulose derivative had delivered 27.3 percent of the available aniline. In the acidic medium and neutral medium 15.6 and 10.6 percent were delivered. After seven days the chitin derivative delivered 27.7, 10.0, and 9.5 percent of the available p-methylaniline in the basic, acidic, and neutral media, respectively.

Cellulose, Amylose and Other Polysaccharide Carbamate Derivatives... 

FIGURE 3 The chemical structures of cellulose benzoate, amylose benzoate, and carbamate derivatives. (From Ref. 32.)... 

Y. Okamoto, M. Kawashima, and K. Hatada, Optical resolution of racemic drugs by chiral HPLC on cellulose and amylose tris(phenyl-carbamate) derivative, J. Liquid Chromatogr., 11 2147 (1988). 

Natural polymers like cellulose and amylose comprise the Type IIIA CSPs, but the mechanical stability of these packings is not sufficiently adequate to be used as a chromatographic sorbent. More satisfactory sorbents have been obtained by chemically modifying them as ester or carbamate derivatives and then coating them onto large-pore silica (300 A) [276]. These CSPs are marketed under the trade names ChiralCel (cellulose) and ChiralPak (amylose). These packings have a wide scope of applications, good stability, and use on a preparative scale. 

Cellulose acid phthalate, I, 320 Cellulose acid succinate, I, 320 Cellulose benzoate, I, 320 Cellulose carbamates, N-derivatives, I, 321... 

Cellulose carbamate and its derivatives are able to immobilize enzymes easily with the help of dialdehydes such as dialdehyde starch, glutaraldehyde, and glyoxal [62]. Since cellulose triphenylcarbamate or tricarbanilate prepared... 

Okamoto and Kaida 99j as well as other research groups also reported the enan-tiodiscrimination ability of CSPs derived from other polysaccharides than cellulose or amylose, including chitosan derivatives 1109.155,1-56], heparin [174], and some others. In some cases chitosan, 3,5-dimethylphenyl carbamate derivatives have shown higher discrimination capability than the cellulose or amylose analogues. 

Microcrystalline cellulose II, like the cellulose I form, does not possess enough mechanical strength to be used as an HPLC-CSP Although its triacetate derivative, CTA-II, can be used as an HPLC support, it is not as useful a CSP as CTA-I (47). Ichida et al. (48) were able to improve on the properties of derivatized cellulose II by depolymerization, followed by coating on macroporous silica gel. In this manner, they created a number of new CSPs, the cellulosic CSPs, based on ester and carbamate derivatives of cellulose (see Table 2). 

In a few cases, the option of preparing tailor-made CSPs for a particular racemic structure has been applied. For example, we prepared on an empirical basis a particular polysaccharide-based CSP for the separation of the enantiomers of the enantiomers of the LTD4 antagonist iralukast and of the antimalaria agent benflumethol [87]. These two racemic drugs were only poorly resolved on the commercially available polysacharide-based phases whereas an excellent separation was obtained on the carbamate derivative of cellulose obtained from cellulose and 3-chloro-4-methylphe-nylisocyanate. The prepared CSP was also used to perform pharmacokinetic studies. 

Yashima, E., Yamamoto, C., Okamoto, Y. NMR studies of chiral discrimination relevant to the liquid chromatographic enantioseparation by a cellulose phenyl-carbamate derivative,/. Am. Chem. Soc., 1996,118, 4036—4048. 

In HPLC, a large variety of analyte types have been resolved on columns packed with derivatized cellulose. Cellulose acetate, benzoate, and carbamate derivatives provide CSPs that will separate a very broad range of analyte types, although a single CSP may not have broad applicability to a wide variety of analytes, and derivatization may be required. Separation is achieved by donor-acceptor interactions, with inclusion phenomena sometimes playing a secondary role. 

The ester and carbamate derivatives of cellulose and amylose are among the most successful and versatile chiral stationary phases for liquid and supercritical fluid chromatography [1,4,28,107-109]. These phases are prepared by reaction of the poly(saccharide) with an acid chloride (ester derivative) or phenylisocyanate (carbamate... 

Heard and Suedee [40] reported the use of cellulose carbamates in stereoselective adsorption and membrane permeation of racemate and individual enantiomers of propranolol. In this study, three carbamates were used including cellulose tris A-(phenyl carbamate) (Ri) cellulose tris A-(3,5-dichlorophenyl carbamate) (R2) and cellulose tris A-(3,5-dimethyl-phenyl carbamate) (R3) (Fig. 4). The S-enantiomer of propranolol was found to be preferentially bound with all the three carbamates used in this study. Further, incubation at 32°C (pH 7.4) increased binding compared to room temperature. The dimethylphenyl carbamate derivative (R3) had the highest sterereoselective binding compared to the dichlorophenyl (R2) and phenyl (Ri) forms. The ratio R to S enantiomer flux values for Ri, R2, and R3 were 2.65, 2.31, and 1.35, respectively. In the control experiment with no carbamates, however, no stereoselective adsorption was observed. 

The R S flux ratios of the enantiomers of propranolol through a silastic membrane of the three cellulose derivatives were equivalent, and the flux rate of the R enantiomer was about twice that of the S enantiomer when pure enantiomers were used. The data for two carbamate derivatives (R2 or 3,5-Cl and R3 or 3,5-CH3) are shown in Fig. 5. Differences in flux values of... 

In practice, it has been found that certain derivatives e.g. tris (3,5-dimethylphenyl carbamate) render the coating less culnerable to solvent dissolution. As a consequence this stationary phase can be used with buffered methanol/water or acetonitrile/water with certain care being taken. Therefore, the tris(3,5-dimethylphenyl carbamate) derivatives of both cellulose and amylose can, with caution, be used in the reversed phase mode. As example of a chiral separation using the different modes is shown in figure 8.6. 

A liquid crystalline system for fibre spinning of cellulose carbamate from NMMO solution is described in reference [55], Cellulose is regenerated analogous to the viscose method (derivative process) and fibres are obtained with strengths of almost 1 GPa and moduli of 49 GPa. Compared to fibre B , a much easier process is used, which is much closer to industrially implemented dope preparation (similar to the viscose process) and spinning procedures (from the NMMO process). 

Cellulose reacted with hexamethylene di-isocyanate to give a carbamate derivative that yielded (20) following hydrolysis and treatment with 0-methyl-isourea. The ionic character of the derivative (20) was used to immobilize... 

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