Dear Alvarez,

You can follow the below procedure for halogenation of α- cyclodextrin which was used by Ashton in 1996 and recently by toomari for halogenation of beta-cyclodextrin.

Procedure: To a solution of Ph3P (2.07 g, 7.9 mmol) under stirring in dry DMF (9 mL), I2 (2.09 g, 8.26 mmol) was added over 30 min. After the addition of I2 the solution temperature increased from room temperature (rt) to 50 ◦C. To this dark brown solution vacuum-dried -CD (1) (0.6 g, 0.53 mmol) was then added, and the reaction mixture was stirred at 70 ◦C under argon atmosphere for 18 h. It was then concentrated through the elimination of DMF (approximately 5 mL) under vacuum and the pH adjusted to 9–10 via the addition of NaOMe in MeOH (3 M, 3 mL) under an argon atmosphere with effective cooling, for 30 min. The precipitate was formed by the addition of reaction mixture into MeOH (40 mL), which was washed with excess MeOH. -CD-(I)7 (0.75 g, 89%) was obtained as a white powder after drying under high vacuum

Reference: https://ac.els-cdn.com/S0144861715005561/1-s2.0-S0144861715005561-main.pdf?_tid=6a3115ae-0153-44ac-8c07-c55b95cff287&acdnat=1524116902_26bb24da344c80feb6e9c12f6cb61a02

AN IMPROVED SYNTHESIS OF PER(6-DEOXYHALO) CYCLODEXTRINS USING N-HALOSUCCINIMIDES - TRIPHENYLPHOSPHINE IN DIMETHYLFORMAMIDE/Chmurski seeattachment

https://books.google.co.uk/books?id=vDLyCAAAQBAJ&pg=PA183&lpg=PA183&dq=AN+IMPROVED+SYNTHESIS+OF+PER(6-DEOXYHALO)CYCLODEXTRINS+USING+N-HALOSUCCINIMIDES&source=bl&ots=vsRQV-_iiN&sig=9xWeKAWcxXG2FVa2O5DfhScClto&hl=de&sa=X&ved=0ahUKEwjF_NmY_8XaAhUIKsAKHUb4AQ4Q6AEITzAE#v=onepage&q=AN%20IMPROVED%20SYNTHESIS%20OF%20PER(6-DEOXYHALO)CYCLODEXTRINS%20USING%20N-HALOSUCCINIMIDES&f=false

Dear Jonathan,

Ravi has written a perfect description but, I would recommend the following modifications:

- use a little less DMF (~60 % of Ravi's description) and use dry (over molecular sieves) DMF;

- during the addition of I2 keep the temperature of the reaction below 40 oC, add the iodine in a rate to keep the temperature limit

- as the I2 addition is finished, stir the solution until its temperature starts to decrease, then add the cyclodextrin

- as the CD addition is finished, elevate the temperature to 70-75 oC

- follow the reaction with TLC and when it is completed, then stir another 2 hours; I am almost sure that 18 hours are much more than it is necessary

- as yous have finished the stirring, cool the reaction mixture 35-40 oC (or you can reduce the amount of DMF as you can) and thed dilute the residual very dense oil with MeOH ~10-15 fold of DMF). Until the solution is acidic, the perhalogenated CD is soluble in MeOH.

- then neutralize with NaOMe/MeOH solution but you can use also solid NaOMe. Check the pH with dropping the MeOH solution to water wetted pH paper. But sometimes you can see the pH change even in the solution: the dark brown solution becomes yellow - by the precipitation of the product (when you are not working on a micromolar scale).

- allow the suspension to stand overnight (or weekend)

- filter and wash the light yellow crystals with MeOH

- dry the crystals at rt for a day

- suspend and stir it in water to remove the excess of base. The product is practically insoluble in water, so the formation of 3,6-anhydro residues practically does not occur

- filter it and wash the solid to neutral with water. The filtration might be slow because of the very fine power

- when the water is neutral (6-7) then wash once with MeOH.

When you are precipitating the product in MeOH instead of DMF the TPPO/TPP remains in solution.

The product is light yellow, contains

Regarding your original question:

For TLC it is better to dissolve it in DMF. But, the load to the TLC is important. Usually you need use less than 40 microg for I6aCD and

"particle sizes of water." Of course I meant the solid precipitated with water. Sorry.