The synthesis of a novel acetylized glycophane

Wang Yu, Fang Zhijie*, Ju Changli ,Wang Yuanxing
(Chemical Engineering School, Nanjing University of Science & Technology, Nanjing,210094)

Received Jul.12, 2004; Supported by the National Natural Science Foundation of China (No.29972020)

2. EXPERIMENTAL
2.1 General Methods
Reactions were monitored by thin-layer chromatography(TLC)(silica gel HSGF₂₅₄ glass sheets).[a]_D value were measured with a WZZ-1 polarimeter. IR spectra were recorded with a Bruker Vector-22 spectrophotometer. NMR spectra were recorded with Bruker DRX300 spectrometer. MS spectra were recorded with Finnigan TSQ-7000.
2.2 Preparation of 1,2,3,4,6-penta-O-acetyl-β-D-glucopyranose 1^[4]
To a solution of anhydrous glucose (5.0g,28mmol) in 25ml acetic anhydride were added anhydrous sodium acetate (4.0g ,48mmol). The mixture was then stirred at 100ºC and in a state of flux for 2h. The solution was poured into 250ml ice-water, and stood for 3h. A precipitate was collected and washed well with water, the yellow powder was dried and then crystallized from ethanol to yield 7.0g white crystal 1(79%). mp:132ºC;_; IR data(KBr)：2970,2914(s,CH₂,CH₃)；1423，1375(s,C-H);1747(s,C=O);1039,1074(s,C-O-C,acid anhydride);1226(s,C-O-C，ether)cm^-1.
2.3 Preparation of 1,4-O-Bis(2,3,4,6- tetra-O-acetyl -β-D -glucopyranosyloxy)benzene 2
To a solution of compound 1(11.7g，30mmol) in CH₂Cl₂(60ml)was added p-benzenediol(1.65g，15mmol)and BF₃.Et₂O(3.75ml),the mixture was stirred for 24h at 25ºC, saturated NaHCO₃(120ml)was added, the organic phase was washed respectively with NaHCO₃ (100ml,5％) and water(100ml), the flavescent solution was dried with anhydrous Na₂SO₄, filtered, and concentrated to give a yellow syrup, which was recrystallized from ethanol to yield 8.2g white powder 2 (67%). mp:181ºC;; NMR data(CDCl₃+TMS): d2.03, d2.05, d2.075, d2.08(4s,24H,8Acetyl), d3.79-3.84(m,2H,H-5/-5'), d4.19-4.32(2dd,4H,H-6/-6'), d4.98, d5.00(d,2H,H-1/-1'), d5.14-5.32(m,6H,H-2,-3,-4/-2',-3',-4'), d6.93(d,4H,Ph).
2.4 Preparation of 1,4-O-Bis(β-D - glucopyranosyloxy)benzene 3 
To a solution of compound 2(1.0g, 1.5mmol) in methanol (10ml, 99.5%) was added sodium methoxide. The mixture was then stirred at 25ºC when the solution was clear. After its standing, the precipitate was collected, filtered to yield 0.6g white crystal 3(100%).mp:230ºC; NMR data(DMSO+TMS): d 6.95(s,4H,Ph); d 5.29(s,2H,H-5/-5'); d 5.07(d,4H,H-6/-6'); d 4.73(d, 2H, H-1/-1'); d 4.57(s,2H,H-3/-3'); d 3.35-3.69(m,4H,H-2,-4/-2',-4'); d 3.19(m,8H,OH).
2.5 Preparation of 1,4-O-Bis(6-O-trityl-2,3,4-tri-O-acetyl-β-D-glucopyranosyloxy) benzene 4  
To a solution of compound 3(1.6g,3.5mmol) in pyridine (40ml)was added triphenylchloromethane(4.0g,14.2mmol),the mixture was then stirred for 6h at 50ºC,the solution was dropped with acetic anhydride(4ml,45mmol),then stirred for 10h at 25ºC. The solution was filtered, one half of the mother solution was evaporated. After its standing for 1h, some rhombic crystal was separated out and filtered. The solution was poured into 200ml ice-water and stirred, a white precipitate was collected, washed well with little ethanol to yield the white powder. Column chromatography(2:1 petroleum ether-acetic ether) of the white powder gave 1.6g 4 (40%).mp:200ºC; NMR data(CDCl₃+TMS): d 1.59-2.10(3s,18H,6 Acetyl); d 3.07-3.27(2dd,4H,H-6/-6'); d 3.64(s,2H,H-5/-5'); d 4.96, d 4.99(d,2H,H-1/-1'); d 5.17-5.29(m,6H，H-2,-3,-4/-2',-3',-4');δ7.06(s,4H,Ph)；δ7.19-7.44(m,30H,2Trityl).
2.6 Preparation of 1,4-O-Bis(2,3,4- tri-O-acetyl -b-D-glucopyranosyloxy)benzene 5
To a solution of compound 4(3.0g,5mmol) in CH₂Cl₂(60ml)was added glacial acetic acid(3.75ml)and chlorhydric acid(0.75ml)，the mixture was stirred for 4h at 5ºC, then added with saturated NaHCO₃(150ml),stirred. Aqueous phase was washed with chloroform (100ml), the organic phase was collected and dried with anhydrous MgSO₄,and concentrated, through column chromatography(2:1 petroleum ether-acetic ether) of it gave 1.3g white powder 5 (76%). mp:210ºC; IR(KBr)data：3465(s,OH),3061(m,C=O),1444(s,CH₃)，1329(s,OH),1156(s,C-O-C), 1009(s,C-O),760,700(s,CH)cm^-1
2.7 Preparation of acetylized glycophane 6   
To a solution of compound 5(0.3g,5.2mmol) in CH₂Cl₂(120ml) was added 1,4-Diazabicyclo[2.2.2]Octane(DACBO)(0.8g,7.1mmol) and terephthalyl chloride(1.1g,5.2mmol), the mixture was stirred for 20min at 0ºC, then for 24h at 25ºC, filtered and the filtrate was distilled under reduced pressure, some white powder was obtained. It was recrystallized from the mixture(1:2 acetic ether-acetone)，then column chromatography(1:1 petroleum ether-acetic ether) of it gave 0.25g white powder 6 (36%). mp:261ºC; ; NMR data(CDCl₃+TMS): d 2.11,d 2.06,d 2.04(3s,36H，12 Acetyl);d 4.44-4.57(2dd,8H,H-6/-6')；d 3.93-3.96(m,4H,H-5/-5'); d 4.77, d 4.79(d,4H,H-1/-1');d 5.01-5.31(m,12H,H-2,-3,-4/-2',-3',-4'); d 7.06(d,8H,Ph); d 8.15 (d,8H,Ph); ESI-MS(m/z) date ( M＝1633):1672 (M＋K).

3. RESULTS AND DISCUSSION       
Because of expensive material and complex procedure for the anterior age in the method of Koenigs-Knorr's^[4], we adopted a modified method－the Helferich method, using the Lewis'acid BF₃^.Et₂O as catalyst to give the compound 2.When used dichloromethane solution, the trityl group on the C-6,6' situs of the compound 4 was eliminated to give the compound 5^[4-9], the modified method was simple and effective.
    The annelation was based on the principle of cyclooligomer' synthesis^[10,11].With pyridine as catalyst, the esterification reaction time was more than 24h, while using DABCO having low steric hindrance and two nitrogen atoms, it was only 15min^[12], all reagents must be fully dried by molecular sieve to prevent acyl chloride from hydrolyzing. 36H between d2.11 and d2.04 showed the compound 6 had 12 Acetyl groups, 28H between d3.93 and d5.31 represented the different H atom at the very site on saccharide groups. 8H for d7.06 indicated the H atom on the 1,4-O-Bis benzene groups, while 8H for d8.15 was on the residual benzene grous. Molecular weight determined by ESI-MS was fitly equal to the data calculated by the designed compound 6.
   The yield of compound 6 was not very high, because the side reaction to produce linear polyester also easily occurred, which can be restrained by the highly-dilution method. For the method, the two reactants need to be diluted by a certain solvent such as benzene, then dropped into bulky solvent isosynchronously and slowly, so the dosage of solvent is higher and the reaction time is longer. A scheme designed by Huang Zaifu can conduce to resolve the disadvantage for the highly-dilution method, he designed a 1.2m tubing where reactants can produce polyester staple in 200s^[13], which will provide us with a reference to enhance the yield in the future. Along with the deacetylation of compound 6 to obtain glycophane, we will study the property and function of its coordinate complex to do truly make extensive use of the glycophane.