2009 03 05 Glucose Anomers

Synthesis of α- and β-glucose pentaacetates Vaardigheden, Hogeschool H ogeschool Utrecht Wouter Nieuwstraten, [email protected]

Date: 2009-03-05

Abstract Two glucose pentaacetate anomers are synthesized using two separate catalysts and acetic anhydride with glucose. Iodine and sodium respectively yield α- and β-glucose pentaacetate. 5Results

and discussion

Glucose exists in equilibrium of two different anom anomer ers; s; α- and and β-gl β-gluc ucos ose. e. The The diff differ eren ence ce  between these two stereo isomers is the location of the the hydr hydrox oxyl yl grou group p on the the C 1-atom. -atom. This 10equilibrium is pH dependant and described in Scheme 1. 1. According to the citations used, the α-glucose is formed in acidic solution, while the β -glucose is formed formed in basic basic solut solution ion.. In neutra neutrall pH, the 15glucose prefers to be in the β-state. This state has less hindrance since all hydroxyl groups are in equatorial position. In the α-state, the C 1-hydroxyl exists in axial position, which is less favorable due to some steric hindrance from the 20C2-hydroxyl.

Scheme 1: Acid-Base equilibrium of α- and β-glucose anomers

The different anomers form because of anomer25ization; the hemiacetal bond (C 1) breaks open to form the aldehyde aldehyde (and alcohol). alcohol). The aldehyde aldehyde will close the ring to form the hemiacetal again. Depend Depending ing on the condit condition ions, s, the hydrox hydroxyl yl group on the hemiacetal will form the α- or β30anomer. When glucose is reacted with acetic anhydride and a catalyst the pentaacetate forms. Depending on the type of catalyst used in the reaction, either α- or β-glucose pentaacetate is synthes35ized. The acetic anhydride reacts with the hydrox droxyl yl grou groups ps in a gene genera rall este esterr reac reacti tion on (Scheme 2). 2).

Scheme 2: Mechanism of esterification with acetic anhyd40ride

Hypothesized is that the sodium acetate in the reaction mixture will not change the pH drastically, but will buffer the acetic acid co-product enough to prevent formation of the α-anomer. iodine has no buffer buffering ing proper propertie ties; s; the 45The iodine solution will become acidic, consequently the α-anomer will form. When the hemiacetal is formed into the more stable acetal (hydroxyl group is converted to an ester/ether), ), the anomerizati anomerization on will not occur  50ester/ether anymor anymore. e. Theref Therefore ore the pentaa pentaaceta cetate te glucos glucosee anomers created can be isolated and tested for  their properties. In total three experiments experiments were performed, performed, of  which h one one expe experi rime ment nt was was perf perfor orme med d with with 55whic galact galactose ose in stead stead of glucos glucose. e. The galacto galactose se  pentaacetate could not be isolated. The found data on all products are displayed in Table 1. To view the experiment experiment description description,, the  Experimental section. section. 60see the Experimental  Table 1: Physical data and constants, all reactions performed with acetic anhydride. Reagents Catalyst Sugar NaOAc D-Glucose I2 D-Glucose I2 D-Galactose

Yield 68% 87%

Product data Appearance Mp. White solid 130°C White ndls. 91°C No isolatable product formed

α/ β β α

The anomers are determined by comparing the H-NMR spectra of the products; according to literature, the resonance peak at 6.6 65the given literature,  ppm for the β-anomer (Figure ( Figure 1) 1) is shifted to 7.3 ppm for the α-anomer (Figure ( Figure 2). 2). 1

The IR spectr spectraa should should be nearly nearly exactly exactly the same same for for both both prod produc ucts ts.. Howe Howeve verr, the the αPage 1 of 3

anomer’s IR spectrum spectrum has a distinctive distinctive hydro70anomer’s

Synthesis of α-D-galactose pentaacetate

gen bridge peak at around 3200. This may be caused by some trapped methanol/water in the crystalline structure of the product. It may also  be caused by some residing hydroxyl peaks, but 75these should have been washed away from the  product.

10 mL of acetic anhydride is added. 2 g of D115galactose is carefully added. While stirring with a magnetic stirrer, add few crystals (max. 0.5 g) of iodine.

The The melti melting ng poin pointt (mp. (mp.)) foun found d unex unexpe pect cted ed  properties in the α-anomer. Instead of a melting  point of 110 °C (Literature ), a melting point of  8091 °C was found. This may correspond to the IR spectrum found earlier, as impurities may (will) lower melting points. In the β-anomer, no abnormalities have been discovered; a melting   point of 130 °C was obtained, while 130-131 85°C was discussed in the synthesis in Literature .

Experimental Synthesis of α-D-glucose pentaacetate

Keep this mixture at room temperature while stirring for at least 40 minutes. When the reac120tion has proceeded, a solution of 10% sodium  bisulfite is added until the solution’s color turns to pale lemon l emon yellow. The remaining solution is mixed with approximately 50 g of ice and is stirred until all ice is 125dissolved. The powder is then filtered off. The filter filtered ed produc productt is recrys recrystall tallized ized from from a 1:2 solution of water/methanol.

Literature 130

1. Blokbo Blokboek ek VC6R VC6R 20082008-200 2009, 9, Vaar Vaardig dig-heden, C. Schneiders, p. 15-17

To a 50 mL round bottomed flask, 10 mL of  acetic anhydride is added. 2 g of D-glucose is 90carefully added. While stirring with a magnetic stirrer, add few crystals (max. 0.5 g) of iodine. Keep this mixture at room temperature while stirring for at least 40 minutes. When the reaction has proceeded, a solution of 10% sodium 95 bisulfite is added until the solution’s color turns to pale lemon yellow. The remaining solution is mixed with approximately 50 g of ice and is stirred until all ice is dissolved. The powder is then filtered off. The filtered d produc productt is recryst recrystalli allized zed from from a 1:2 100 100filtere solution of water/methanol.

Synthesis of β-D-glucose pentaacetate To a 50 mL round bottomed flask, 2.5 g of Dglucose and 2 g of sodium acetate is added. Add 105 10512.5 mL acetic anhydride and apply cooler to flask. Heat the mixture to 100°C for 1.5 hours while stirring. After the reaction, mix the solution with 125 mL of ice water (0°C!). Keep mixing at 0°C for  110another 10 minutes. Filter off the product and recrystall allized from a 1:2 solution of  water/methanol.

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Appendix

Figure Figure 4: IR of the pentaace pentaacetate tate formed formed with iodine as the catalyst.

Figure 1: 1H-NMR of the pentaacetate in CDCl 3 formed with sodium acetate. The anomer formed is the β-anomer.

135 Figure 2: 1H-NMR of the pentaacetate in CDCl 3 formed with iodine as catalyst. The anomer formed is the α -anomer.

140 140Figure

3: IR of the pentaacetate formed with sodium acet-

ate.

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