6 Sulphonic Acid Esters Typical structures of sulphonic acid esters used in polysaccharide chemistry are showninFig.6.1.Themostwidelyusedarethep-toluenesulphonic- and the methanesulphonic acid esters, due to their availability and hydrolytic stability. The formation of sulphonic acid esters is carried out heterogeneously by conversion with sulphonic acid chlorides in a tertiary organic base, in aqueous alkaline media (NaOH, Schotten-Baumann reaction), or completely homogeneous in a solvent such as DMAc/LiCl. A major drawback of heterogeneous procedures is that long reaction times and a high molar excess of reagent, mostly sulphonic acid chloride, are necessary for significant conversion. Sulphonic acid esters are reactive and may be attacked by unmodified OH groups in situ, yielding cross-links. Hence, the products obtained are insoluble. In addition, they contain a high chlorine content formed by the nucleophilic attack of chloride ions. In contrast, the homogeneous conversion, e.g. of cellulose dissolved in DMAc/LiCl, yields soluble sulphonic acid esters [162]. In particular, homogeneous tosylation applying TosCl in the presence of TEA is very efficient. It is well known from the chemistry of low-molecular alcohols that hydroxyl functionsareconvertedtoagoodleavinggroupbytheformationofthecorre- sponding sulphonic acid esters, and hence nucleophilic displacement reactions can be carried out. In the case of polysaccharides, nucleophiles such as halide ions may attack the carbon atom, leading to the corresponding deoxy compound with substitution of the sulphonate group (Fig. 6.2). It is also possible to modify the remaining hydroxyl groups prior to the S N reaction. 6.1 Mesylates The heterogeneous conversion of mercerised cellulose (cotton linters) with MesCl (6 mol per mol AGU) in Py slurry affords cellulose mesylate with DS Mes values up to 1.7 after reaction for several days at RT [264]. A crucial point is the activation of the starting cellulose. It was found that the treatment of cellulose with aqueous NaOH increases the reactivity [264]. In order to gain higher DS values, subsequent solvent exchange with anhydrous methanol and Py is necessary. The alkali content of the activated cellulose on the DS Mes is unimportant (Table 6.1). 118 6 Sulphonic Acid Esters Fig. 6.1. Typical sulphonic acid esters of polysaccharides Table 6.1. Influence of reaction time and temperature on the conversion of mercerised cellulose (cotton linters) with MesCl in Py (adapted from [265]) Conditions Reaction product Time (h) Temperature (°C) S (%) Cl (%) DS Mes DS Cl 4 28 20.0 1.42 2.00 0.11 17 28 23.0 2.91 2.74 0.29 2 57 12.0 10.73 0.93 0.72 20 57 12.5 12.93 1.00 0.86 6.1 Mesylates 119 Fig. 6.2. Typical examples for S N reactions of polysaccharide sulphonic acid esters The mesylation proceeds readily at 28 ◦ C; at an elevated temperature of 57 ◦ C, side reactions become predominant, yielding products of comparably low DS Mes but with a high content of chlorodeoxy moieties [265]. The conversion of cellulose with MesCl in the presence of TEA in DMAc/LiCl yields products with a DS Mes of 1.3 at areactiontemperatureof7 ◦ C for 24 h (Table 6.2, [266]). By a subsequent mesylation, a DS Mes of 2.1 may be realised [267]. A disadvantage of the homogeneous mesylation is the fact that the reaction has to be carried out at polymer concentrations lower than 1% in order to prevent Table 6.2. Conversion of cellulose with MesCl homogeneously in DMAc/LiCl at a temperature of 7 °C (adapted from [267]) Conditions Reaction product Molar ratio AGU MesCl TEA Time (h) S (%) Cl (%) DS Mes DS Cl 1 9 18 24 15.8 1.4 1.3 0.10 1 9 18 48 14.4 2.8 1.2 0.20 1 15 30 24 15.5 1.0 1.3 0.06 1 15 30 48 15.3 0.5 1.3 0.04 120 6 Sulphonic Acid Esters gelation during the addition of the reagent. The products have to be precipitated and washed carefully with ethanol/hexane or methanol/acetic acid. The pH value has to be maintained around 7 in order to prevent hydrolysis of the ester moieties. The cellulose mesylates were found to be soluble in DMSO starting at DS Mes 1.3, and additionally in DMF and NMP starting at DS Mes 2.1. Samples with lower DS Mes swell only. Dextran mesylate is prepared in an aqueous solution of the biopolymer with MesCl and NaOH as base [262]. Precipitation in ethanol yielded a dextran mesy- late, which is partly water soluble. The water-soluble fraction (main component) possesses a DS Mes of 0.10, while the DS Mes of the insoluble part is 0.68. The structure of the reaction products of cross-linked pullulan particles with MesCldependsonthesolventused.InthecaseofPy,mesylationat20 ◦ C yields apullulanmesylatewithDS Mes 0.68 and negligible incorporation of chlorodeoxy groups (DS Cl 0.04), applying 3 mol reagent per mol RU. At higher temperatures, S N reactions become predominant, decreasing the DS Mes and increasing the DS Cl .In contrast, mesylation in DMAc and DMF yields products containing both mesyl and chlorodeoxy moieties already at a low reaction temperature [268]. For instance, if the reaction is carried out in DMF at 20 ◦ C,aDS Mes of 0.04 and a DS Cl of 0.10 were obtained. 6.2 Tosylates Tosylationofcellulosecan be carried outhomogeneously in the solventDMAc/LiCl, permitting the preparation of cellulose qtosylate with defined DS Tos controlled by the molar ratio reagent to AGU at short reaction times, with almost no side reactions [162, 256, 271]. However, the product structure may depend on both the reaction conditions and the workup procedure applied (Fig. 6.3). Sulphonic acid chloride and DMAc react in a Vilsmeier-Haack-type reaction forming the O-(p-toluenesulphonyl)-N,N-dimethylacetiminium salt I. This inter- mediate reacts with hydroxyl groups, depending on the conditions applied. Using weak organic bases, e.g. Py (pK a 5.25) or N,N-dimethylaniline (pK a 5.15), the reac- tion with the polysaccharide yields a reactive N,N-dimethylacetiminium salt II. II can form chlorodeoxy compounds III at high temperatures or yields the acetylated polysaccharide IV after aqueous workup. In contrast, stronger bases such as TEA (pK a 10.65) or DMAP (pK a 9.70) react with I, yielding a less reactive species V compared with II, and hence lead to the formation of polysaccharide sulphonic acid esters VI without undesired side reactions. Detailed studies on the preparation of cellulose tosylates demonstrate that various cellulose materials with DP values ranging from 280 to 1020 could be converted to the corresponding tosyl esters [256]. At 8–10 ◦ C,DS Tos values in the range 0.4–2.3, with negligible incorporation of chlorodeoxy groups, were obtained within 5–24 h (Fig. 6.4, Table 6.3). The cellulose tosylates are soluble in a wide variety of organic solvents. From DS Tos 0.4, they dissolve in aprotic dipolar solvents (DMAc, DMF, and DMSO). The 6.2 Tosylates 121 Fig. 6.3. Mechanism for the reaction of cellulose with TosCl in DMAc/LiCl depending on organic bases (adapted from [272]) polymer becomes soluble in acetone and dioxane at DS Tos 1.4 and, in addition, in chloroform and methylenechloride at DS Tos 1.8. A structure characterisation was carried out by means of FTIR- and NMR spectroscopy (Fig. 6.5). In the 13 C NMR spectra (Fig. 6.5), typical signals of the modified AGU are observed in the range from 61.0 to 103.0 ppm.Inaddition,thepeaksofthetosyl ester moiety can be found at 20.5 ppm (methyl group) and in the range from 127.0 to 145.0 ppm (aromatic carbon atoms). It is obvious that position 6 is esterified first because a signal appears at 70 ppm, which is caused by the functionalisation. Significant splitting of the C-1 signal was not detected, indicating that position 2doesnotreactatlowDS Tos . With increasing DS Tos , the intensity of the C-6 122 6 Sulphonic Acid Esters Fig. 6.4. Time dependence of the con- version of cellulose with a molar ra- tio AGU:TosCl of A 1:6 and B 1:1 in DMAc/LiCl solution in the presence of TEA Table 6.3. Reaction of cellulose with TosCl in DMAc/LiCl for 24 h at 8 °C (adapted from [257]) Reaction conditions Reaction product Molar ratio Cellulose DP AGU TosCl TEA DS Tos S(%) Cl(%) Microcrystalline 280 1.0 1.8 3.6 1.36 11.69 0.47 1.0 4.5 9.0 2.30 14.20 0.43 Spruce sulphite pulp 650 1.0 1.8 3.6 1.34 11.68 0.44 1.0 9.0 18.0 1.84 13.25 0.49 Cotton linters 850 1.0 0.6 1.2 0.38 5.51 0.35 1.0 1.2 2.4 0.89 9.50 0.50 1.0 2.1 4.2 1.74 12.90 0.40 1.0 3.0 6.0 2.04 13.74 0.50 Beech sulphite pulp 1020 1.0 1.8 3.6 1.52 12.25 0.43 peak decreases considerably until almost complete disappearance at DS Tos 1.89. In addition, another signal for C-1 appears (C-1  ), which is caused by substituents at position 2. The heterogeneous conversion of starch with TosCl in Py slurry yields starch tosylates of low DS. In this procedure, the starch is activated by treatment with aqueous Py, followed by solvent exchange. The reactivity of the hydroxyl groups is in the order O-6>O-2>O-3 [258]. Using DMAc/LiCl as solvent in the presence of TEA at 8 ◦ C, pure starch tosylates can be prepared (Table 6.4, [259]). Compared to cellulose, a low LiCl concentration of 1% is sufficient to dissolve the polymer. Starch tosylates with DS Tos values ranging from 0.6 to 2.0 are accessible with chlorine contents lower than 0.42%. Reactions at room temperature and with increased amount of reagent lead to products with a lower DS Tos , and the chlorine content is remarkably increased 6.2 Tosylates 123 Fig. 6.5. 13 C NMR spectra of cellulose tosylates with DS Tos 0.40, a 1.12 and b 1.89 in DMSO-d 6 . The dash (  ) means influenced by substitution of the neighbouring position and subscript s means substituted position Table 6.4. Homogeneous conversion of starch (Hylon VII, 70% amylose) with TosCl in DMAc/LiCl (24 h, adapted from [259]) Reaction conditions Reaction product Molar ratio Temperature AGU TosCl TEA (°C) DS S S(%) Cl(%) 1.0 1.0 2.0 8 0.61 7.61 0.19 1.0 1.5 3.0 8 1.02 10.18 0.20 1.0 2.0 4.0 8 1.35 11.64 0.30 1.0 3.0 6.0 8 1.43 11.93 0.42 1.0 6.0 12.0 8 2.02 13.61 0.32 1.0 1.0 2.0 20 0.61 7.63 0.11 1.0 1.5 3.0 20 0.87 9.40 0.43 1.0 2.0 4.0 20 0.71 8.38 0.45 1.0 3.0 6.0 20 1.27 11.34 1.33 1.0 4.0 8.0 20 1.26 11.30 1.55 1.0 6.0 12.0 20 1.76 12.96 1.48 124 6 Sulphonic Acid Esters due to the formation of chlorodeoxy moieties caused by nucleophilic displacement reactions. The starch tosylates are soluble in a variety of solvents. Starting with DS Tos 0.61, they dissolvein aprotic dipolar solventssuch as DMAc, DMF and DMSO. The solubility in less polar solvents begins at DS Tos 0.98 in dioxane and at DS Tos 1.15 in THF. A polymer with DS Tos 2.02 can be dissolved in chloroform. Arepresentative 13 C NMR spectrum of a starch tosylate with DS Tos 1.09 is shown in Fig. 6.6. Tosylation leads to a downfield shift of about 8.5 ppm, and hence the carbon atom of the tosylated position C-6 can be found at 69.0 ppm. Additionally, functionalisation of the secondary hydroxyl groups causes signals at 80.2 ppm.It is important to note that an intensive peak appears at 94.3 ppm,whichisassigned as C-1  , indicating a fully substituted position 2 already at a total DS Tos of 1.09. In contrast to heterogeneous reaction (O-6>O-2/O-3),areactivityintheorder O-2>O-6/O-3 appears. Fig. 6.6. 13 C NMR spectrum of starch tosylate with DS Tos 1.09, recorded in DMSO-d 6 at 60 °C (reprinted from Carbohydr Polym 42, Heinze et al., Starch derivatives of high degree of functionalization. 1. Effec- tive, homogeneous synthesis of p-toluenesulfonyl (tosyl) starch with a new functionalization pattern, pp 411–420, copyright (2000) with permission from Elsevier) Detailed information about the functionalisation pattern of starch tosylates can be obtained by NMR spectroscopy of the peracylated polymers. 1 H NMR spectra of peracetylated starch tosylates are shown in Fig. 6.7. The signal at 4.8 ppm is assigned to an acetylated position 2 (H-2), applying two-dimensional NMR methods [273]. The intensity of the H-2 signal decreases with increasing DS Tos . Starting with DS Tos 1.02, the peak disappears.Thus, the tosylation occurs preferably at the hydroxyl group at position 2. This tosylated position undergoes S N reactions 6.2 Tosylates 125 Fig. 6.7. 1 H NMR spectra from acetylated starch tosylates of different DS Tos and DS Ac . The spectral range shown (3–6 ppm) is specific for the modified AGU (reprinted from Carbohydr Polym 45, Dicke et al., Starch derivatives of high degree of substitution. Part 2. Determination of the functionalization pattern of p-toluenesulfonylstarch by peracylation and NMR spectroscopy, pp 43–51, copyright (2001) with permission from Elsevier) to a limited extent only. Nucleophilic displacement reactions starting from starch tosylate are not reasonable because a high DS Tos is required to ensure tosylation of the primary OH group. Chitin possesses two different reaction sites that can be attacked by the sul- phonic acid chloride (Fig. 6.8). There are OH groups forming the corresponding ester and NH 2 moieties leading to N-sulphonamide, which are not susceptible for S N reactions. Chitin tosylate, a versatile derivative for subsequent reactions, can be synthesised by homogeneous or heterogeneous processes [103]. Iododeoxy- and mercaptodeoxy chitin are accessible as precursors for, e.g. graft copolymerisation with styrene [274, 275]. In order to prevent N-tosylation, applying pyridine as reaction medium and a high excess of TosCl (10 mol / mol repeating unit), products with DS Tos up to 0.83 are obtained as a white fibrous material (Table 6.5). DMAP promotes the tosylation reaction, and no N-deacetylation occurs under these mild conditions. α -Chitin isolated from shrimp is remarkably less reactive, compared with β -chitin from squid pens. 126 6 Sulphonic Acid Esters Fig. 6.8. Different types of sulphonic acid derivatives of the 2-deoxy-2-amino repeat- ing unit in chitin Table 6.5. Preparation of chitin tosylates heterogeneously starting from N-acetyl chitin (0.2 g) in Py in the presence of DMAP (adapted from [103]) Chitin Reaction conditions Chitin tosylate Source Type DMAP (g) Time (h) DS Squid β 0 24 0.34 Squid β 0 48 0.69 Squid β 0.2 24 0.62 Squid β 0.2 48 0.70 Squid β 1.0 48 0.80 Squid β 2.0 48 0.83 Shrimp α 0.2 48 0.18 In a homogeneous procedure, chitin (DDA 0.18) is converted to alkali chitin by treatment with 42% aqueous sodium hydroxide [260]. A solution is obtained after addition of crushed ice. A biphasic mixture is formed with a solution of TosCl in chloroform by vigorously stirring for 2 h at 0 ◦ C and 2 h at 20 ◦ C. After workup, chitin tosylates with DS Tos up to 1.01 were obtained (Table 6.6). The possibility of Table 6.6. Homogeneous preparation of chitin tosylates starting from alkali chitin (adapted from [260]) Molar ratio Chitin O-tosylate Repeating unit TosCl DS Tos Solubility 1 7 0.42 DMSO, DMAc, NMP, HCOOH, 1 10 0.73 DMSO, DMAc, NMP, HPMA, HCOOH 1 15 0.95 n.d. 1 20 1.01 n.d. [...]... the authors’ point of view The few examples found in the literature are summarised in Table 6.7 128 6 Sulphonic Acid Esters 6.3 Miscellaneous Sulphonic Acid Esters Various other aromatic or aliphatic sulphonic acid chlorides have been reacted with polysaccharides Substituted benzenesulphonic acid esters of cellulose are investigated in terms of the SN reaction with lithium acetate, and a reaction mechanism... fluorescence spectroscopy The fluorine-containing aliphatic sulphonic acid esters of polysaccharides exhibit a high reactivity and have to be handled carefully The conversion of trifluoromethanesulphonic acid anhydride with methyl cellulose and cellulose acetate was used for the preparation of cross-linked gels [269] 2,2,2-trifluoroethanesulphonic acid chloride was found to be a useful reagent for improving... improving the affinity for cellulose acetate membranes for enzyme immobilisation [270] Starting from cellulose 2,2,2-trifluoroethanesulphonic acid ester, deoxyaminocelluloses with chromophoric properties as carrier matrices were prepared [283] Cellulose esters bearing aminoaryl sulphonic acid may have useful optical properties (fluorescence) [263] ... SN reaction is somewhat limited It has also to be taken into account that nucleophils possess a different reactivity The azide ion is much more nucleophilic than the iodide ion, and therefore also sulphonic acid ester moieties bound to secondary OH groups can be displaced In addition, α-(1 → 6) linked polysaccharides (e.g dextran) may contain also branches with primary OH moieties at the end groups as . in Table 6.7. 128 6 Sulphonic Acid Esters 6.3 Miscellaneous Sulphonic Acid Esters Various other aromatic or aliphatic sulphonic acid chlorides have been. Sulphonic Acid Esters Typical structures of sulphonic acid esters used in polysaccharide chemistry are showninFig.6.1.Themostwidelyusedarethep-toluenesulphonic-