Methylated CD

The most common way to produce MCD is the dimethyl sulfate method. The 

Dissolve 2 g sodium hydroxide into 30 mL deionized water which contained 10 g /3-CD. Then add 5mL dimethyl sulfate slowly with stirring. Keep reaction system at 60°C for 8h. After that, cool the reaction buffer and adjust to neutral using diluted HCl. Then remove anions and cations through ion exchange resins (repeat 2 or 3 times). Concentrate the collected liquid to a syrup-like state by vacuum distillation. Finally, disperse the product in 40 mL acetone and vacuum dry to get the product. 

At present, the preparation of fully replaced MCD is mostly one-step. The detailed process is as follows Load 30 mL dimethyl sulfoxide (DMSO) in 50 mL-three neck flask. Add fi-CD and stir for 1 h. After -CD is fully dissolved, add 0.6 g sodium hydride under the protection by nitrogen. Drop double amount of methyl iodide to the buffer. The reaction lasts for 5 h at 60°C. Stop the reaction and add sodium hydride. Extract the product by ether three times. Evaporate the ether, get the crude product, wash it using chloroform and methanol (100 2) and separate via silica gel column. The final yield could reach to 54%. 

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Fig. 17.4 Chromatographic behaviour of dihydroactinidiolide (DHA) enantiomers synthetic racemate (a) DHA fractionation by enantioselective high-performance liquid chromatography (HPLC) (b). Chiral selectors used in enantio-GC DIME-jS-CD (30%) in SE 52 DIAC-jS-CD (30%) in PS 268 DIAC-/1-CD (50%) in OV 1701. Order of elution R (I), S (II) in all cases [13], DIME heptakis(2,3-di-0-methyl), CD cylclodextrin, DIAC heptakis(2,3-di-0-acetyl)...

The solubility of underivatized CDs generally increases with increasing temperature. On the other hand, the aqueous solubility of methylated CDs is inversely proportional to temperature. An increase in temperature may cause the dehydration of methylated CDs in a mannersimilarto nonionic surfactants (Uekama, 1985). 

Thujene l-Iaopropyl-4-methyl CD bicyclo Q3. l.OOhex-2-ene 2-Thujene... 

The method surveyed seems to be advantageous and to some extent complementary to the important methods in which the commercially available CD silica stationary phases are used. Moreover it involves sometimes additional factors which could improve separation such as adsorption on an RP phase or second stage complexation. The surveyed method has not been totally explored both in theory and/or in practice. The newest results achieved via methylated CD s confirm this opinion(38,39). Therefore still it is to early to draw general conclusions. ... 

Studies suggest that an optimal definition for a commercially viable methylated CD is the partially methylated p-CD (Ml4-p-CD) containing an average MS of approximately 14 with the substituents at the 2-, 3-, and 6-positions. This material is produced economically, has an aqueous solubility that increases with temperature, and has binding constants higher than those observed with the unsubstituted p-CD and close to those observed with the 2,6-DM-p-CD. 

Fig. 2 Influence of cyclodextrin type on the chiral resolution of the basic drug tocainide and related substances using 40 mM sodium phosphate (pH 3.0) containing (a) 20 mM -CD and (b) 50 mM methyl- -CD and 50 mM heptakis (2,6 di-O-methyl-jS-CD. [Adopted with kind permission from D. Beider and G. Schomburg, Chiral separations of basic and acidic compounds in modified capillaries using cyclodextrin-modified capillary zone electrophoresis, J. Chromatogr. A 666 351 (1994).]...

Recently, Pongratz and Heumann have shown that besides methylated Hg and Pb also monomethyl-Cd can be detected in the polar ocean (10, 11, 24). Because the experiments with polar macroalgae did not show any production of methylated Cd, it must be assumed that other marine organisms are responsible for the existence of MeCd in the ocean. Incubation experiments with isolated mixed and pure bacterial cultures of polar origin, collected in the Weddell Sea, were therefore carried out and the production of methylated heavy metal eompounds was followed during the growth of these baeteria. The total (inorganic) heavy metal concentration of the natural sea water from the Weddell Sea, used in these... 

Figure 7.19. East-west concentration profiles of methylated Cd, Pb and Hg and of Chlor-ophyll-a in surface sea water samples on an expedition from Cape Town to Punta Arenas (7, 24) (chlorophyll-a concentrations from (58)).

Figure 7.20 illustrates a west-east concentration profile (from left to right of the plot) at a latitude of about 68° S (west of the Antarctic Peninsula) of methylated Cd, Pb and Hg in surface sea water samples (7, 24) analyzed during April 1995. Chlorophyll-fl was determined by Templin and Bathmann (59). This profile is divided into two different areas, one characterized by pack-ice from 98° W to 84° W, the other one by a totally closed ice sheet from 84° W to 68° W. In the pack-ice section, the methylated heavy metal compounds could normally be determined with concentrations distinctly above the detection limit, whereas in the polar ocean under the closed ice sheet methylated heavy metals were mostly below or at the detection limit, except small concentrations near the shore of the Antarctic Peninsula (right side of Figure 7.20). 

Gelation Induced by Physical Interaction of Threaded Methylated CDs in Polyrotaxanes... 

Fig. 18 a, b Schematic illustration of the sol-gel transition of the polyrotaxane of methylated a-CD in Water. There are isolated chains and only limited clusters of polyrotaxane in the solution at lower temperature a and large number of crosslinks consisting of crystal-like aggregates among localized methylated CDs in the gel at higher temperatures b [87]... 

Modifier The effect of the modifier structure is also quite similar to that found for a-ketoesters [7]. Cinchonidine derivatives and quinine lead to an excess of the (R)-hydroxy-acid while the pseudo-enantiomeric cinchona alkaloids (cinchonine and quinidine) give preferentially (S)-product but with much lower enantioselecdvity. Changing the substituent Y at C9 has only an effect on the degree of asymmetric induction but not its direction. OMe and OH are more effective than OAc or H. An interesting exception are the Nj alkylated Cd derivatives which are completely ineffective in the case of the ester. Here, N-methyl-Cd+Cr gives a small excess of the R-enantiomer while N-benzyl-Cd Cl leads an 33% excess of (S)-4-phenyl-2-hydroxybutyric acid ... 

Nevertheless, it must be pointed out that the formation of such transient species has never been spectroscopically observed. Native CDs are effective inverse phase-transfer catalysts for the deoxygenation of allylic alcohols, epoxydation,or oxidation " of olefins, reduction of a,/ -unsaturated acids,a-keto ester,conjugated dienes,or aryl alkyl ketones.Interestingly, chemically modified CDs like the partially 0-methylated CDs show a better catalytic activity than native CDs in numerous reactions such as the Wacker oxidation,hydrogenation of aldehydes,Suzuki cross-coupling reaction, hydroformylation, " or hydrocarboxylation of olefins. Methylated /3-CDs were also used successfully to perform substrate-selective reactions in a two-phase system. 

The complexes of 2,3 (sodium salt) and 4 (potassium salt) with P-CD and (2,3,6- tri-0-methyl)-/ -CD were studi using steady-state fluorescence and time-correlated, single-photon counting techniques [52]. The formation of both 1 1 and 2 1 complexes between p-CD and 2,3 was confirmed. Trimethyl- -CD gave evidence only of 1 1 complexes. The fluorescence decay of systems giving exclusively 1 1 complexes was collected at CD concentrations that ensure more than 90% complexation. The analysis performed using a continuous lifetime distribution model... 

The (S) enantiomer of l,l -bis-2-naphthol (9) 2,2 -dimethoxy-l,T-binaph-thyl, and l,T-binaphthyl-2,2 -diyl hydrogen phosphate were preferentially included by heptakis(2,3,6 tri-0-methyl)-/ -CD [82]. Addition of CD to the (S)-enantiomer caused fluorescence enhancement higher than that observed for the (J )-enantiomer. Moreover, the complex between the trimethyl- -CD and (S)-9 was found to have a stoichiometry of 2 1 while the complex with (J )-g has 1 1 stoichiometry. Unsubstituted jS-CD did not give enantioselec-tive complexation. 

Leigh et al. [292] explained the excited-state behavior of p-(4-hy-droxyphenyl)ethoxyacetophenone, 111, in a-,/ - and y-2,6-di(0-methyl)CD complexes using similar arguments. In this system, quenching of the triplet state occurred by H-abstraction of the phenolic hydrogen when the conformation of the inclusion complex allowed end-to-end contact. This occurs for p-CD complexes a- and y-CD complexes are unreactive [292]. 

In a study on the vinylation of methyl ethyl ethers were successfully s arated as the trimethylsilyl ethers of the methyl 0-ethylglycosides. ... 

Randomly hydroxylated and methylated CD (RM-yS-CD) with different cavity sizes have been used as biphasic aqueous catalysts in a palladium catalyzed Tsuji-Trost reaction with water-insoluble alkylallylcarbonates and alkylallylurethanes as substrates (Figure 4.6c). The reaction rate and substrate selectivity strongly depended on the cavity size of the CD. The cavity size is a crucial factor in controlling the substrate selectivity. Moreover, phosphanes that did not interact with the methylated CD were the most... 

Figure 4.7 Suzuki-reactions mediated by P-CD or Randomly Methylated CD (RM-P-CD) in the presence of metal catalyst in aqueous solution, a R = NO2, OH, OCH3, COCH3,...

The so-called first-generation cyclodextrin (CD), i.e. the native a-CD, -CD and y-CD, each has its limitations in application. -CD exhibits poor solubility a-CD owns a small cavity which restricts the size of the guest molecules y-CD has a larger cavity but expensive. Thus, to expand the application area, native CDs are usually modified to improve their physiochemical properties [ 1 ]. Until now, various branched-CDs, such as methyl-CD, hydroxypropyl-CD, glucosyl-CD (Gl-CD) and maltosyl-CD (Mal-CD) have already been commercialized. 

It is reported that acetylation or methylation CD treated by PhsTMs-Znl2 can cleave only one C-C bond and generate high yield of malto-oligosaccharide. The internal cyclization would occur on this modified malto-oligosaccharides to produce new single-modified CDs. 

The industrial MCD is a mixture of different kinds of partly replaced methyl CD derivatives. The separation and purification process is relatively simple, and mainly aims at removing the salts and unreacted raw materials from the reaction solution. Salt is removed by ion exchange resin for several times. The un-reacted raw materials are usually neutralized by ammonia water or steamed [ 19]. 

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