as you know, cyclodextrins have a 3 reactive alcohols. 2-OH, 3-OH and 6-OH, I am gonna to bind 2 molecules to them. what should i do?
I think, it is not about "3 reactive alcohols" but hydroxyl groups in positions 2, 3 and 6. Groups in position 6 have more alkali properties than in position 2. It has also been shown that groups in position 3 are harder to access than in position 2 and 6. Many methods for modifying cyclodextrins are described in the scientific literature by blocking individual groups. However, selective reactions of hydroxyl groups eg with an acid is difficult. Simultaneous chemical reaction of 2 and 6 hydroxyl groups? Unlikely. Rather in series. In addition, acids are usually esterified with alcohols, not vice versa. Regards,
The short answer is YES. But ...
Although it is true that in esterification the O(6) is usually more active but, depending on the size of the molecule the O(3) can be also reactive. The steric hindrance of O(3) is more expressed when the ionization of the OH groups are needed - of course, bulky substituents, like Tr cannot react -, AND the O(2) is substituted. Another example is the tosylation of CDs in pyridine with TsCl. If you want to prepare mono-6-OTs, you need to do some preliminary experiments to find an optimal conditions for the max. yield of 6-OTs because O(2) and O(3) is also tosylated upon longer (>1 h) reaction.
If you have O(2) protected CD which is relatively stable (i.e. not TBDMS and the like or ester appended) and you want to esterify with a liquid anhydride then I would recommend the use of FeCl3*6H2O as (Lewis acid) catalyst. Usually 0.3-1.0 molar excess of anhydride/OH is enough
In case of Ac2O and FeCl3 the O(3) acylation is so fast that partial esterification not, only peracetylation could be achieved.
This method can be used also for even the butyrylation of per-2,6-dipentylation cyclodextrins.
The only drawback of the method is that - particularly when alkylated CDs are the subject of reaction - the opening of the macrocycle.To suppress the Lewis acid catalyzed glycolysis the parent acid (and lower than r.t.) can be used. For example in the mentioned butyrylation you need to cool the reaction mixture below 20 oC, use 1:1 mixture of butyric acid and butyric anhydride, and "spoonwise" addition of the CD; stop the reaction after 10 min otherwise a considerable part of the macrocycle opens (no inprocess control is possible). Or, in the per 3-O acylation of DIMEB requires some tricks, otherwise the very efficient synthesis of 2,6-di-O-methyl-1,3,4-triacetyl-Glcp is realized :) in a minute. The longer reaction times and/or higher (uncontrolled) temperature opens the pyranose ring.
Of course if there is/are another ester groups on the CD they are usually exchanged.
The method is also working with (liquid) acid chlorides but you need to remove the formed HCl e.g. with N2 or Ar. Per-3-O-palmitoyl-DIMEB can be prepared by this was, too.
If you need more details, contact me.
Good luck,
Laszlo
Lack of selectivity and even randomness may also be associated with the number of glucose units. The more mers, the more hydroxyl groups. Fortunately, there is no here (6-8 units) such situation as in the case of starch modification using organic acids. Regards,
- Badges
- Science topic
- Similar topics
- Biological Science
- Biochemistry
- Biochemical Techniques
- Analytical Chemistry
- pH