Organic Chemistry Portal
Organic Chemistry Highlights

Ultrasound Chemistry

Saturday, July 25, 2009
Ricardo A. W. Neves Filho1), Ronaldo N. de Oliveira2)
1) Universidade Federal de Pernambuco, 2) Universidade Federal Rural de Pernambuco

Part 2: Application of Ultrasound Irradiation in Carbohydrate Synthesis

Ultrasound energy: a powerful tool for carbohydrate synthesis

Chang and co-workers from Utah State University, USA, have demonstrated that a large number of conventional reactions commonly employed for the synthesis and/or functionalization of carbohydrates may be performed under ultrasound irradiation with remarkable results in terms of yields and reaction time. (J. Org. Chem. 2006, 71, 5179. DOI: 10.1021/jo060374w) For example, ultrasound-mediated acetylation of hydroxyl groups could be accomplished in several minutes instead hours required by conventional methods. It is noteworthy that even the hindered disaccharide trehalose underwent the reaction to afford the desired acetylated sugar in good yield. Other procedures such as tosylation and diol protection have worked well by employing such acoustic techniques.

Deprotection reactions can also be carried out sonochemically. This way, the cleavage of acetyl and benzylidene groups has been achieved in good yield after a few minutes. Interestingly, even deprotection of the trityl group could be achieved smoothly in almost quantitative yield in 12 minutes; whereas the cleavage of such groups generally demands harsher conditions, it is clear that ultrasound irradiation helps the reaction proceed to completion.

The same group reported earlier that some acyl group migrations within the carbohydrate scaffold take hours or even days for reaction completion. (Synlett 2006, 756. DOI: 10.1055/s-2006-933105) However, sound-wave activation promotes a substantial enhancement in the reaction rate; therefore, the procedure afforded the desired products in several minutes and in good yield under such conditions.

Ultrasound irradiation applied to glucose oligomerization

In 2001, the group of Yves Queneau and co-workers discovered a new technique for glucose oligomerization. (Ultrason. Sonochem. 2000, 7, 157. DOI: 10.1016/S1350-4177(99)00035-8) Firstly, they were interested in developing the montmorillonite KSF-catalyzed glycosylation reaction of butanol and dodecanol under ultrasound irradiation. Nevertheless, they have found that sound-wave activation had no significant effect on the glycosylation of butanol, even when using homogeneous or heterogeneous catalysts. In the case of dodecanol glycosylation, it was found that reaction under conventional stirring leads to formation of glycosides preferably, however by employing ultrasound irradiation the autoglycosylation process took place almost exclusively, and the oligomers precipitated out from the solution. Furthermore, after a structural analysis it was found that the oligomers obtained using the acoustic technique were longer than the ones obtained under silent conditions.

Sonication-assisted oligomannoside synthesis

Christabel T. Tanifum and Cheng-Wei T. Chang from Utah State University, USA, disclosed a new protocol to get oligomannosides in good yields, short reaction times and high stereoselectivity. (J. Org. Chem.,2009, 74, 634. DOI: 10.1021/jo8019835) In the first part of their article they evaluated the influence of protecting group as well as solvent on the glycosylation of 6-azidohexanol by using a 1-thio-R-D-mannopyranoside as donor. It was found that in most of cases they observed the selective formation of α-glycosides. In an attempt to improve the amount of the α-anomer they tested a 4,6-O-benzilidene protected sugar. Nevertheless, this effort failed and the α-product was formed exclusively. Based upon this fact, the authors suggest that the sonication energy is strong enough to overcome the conformational barrier imposed by the protecting group. Therefore, the use of such an energy source is essential to keep the α-selectivity of the reaction. Finally, they proceeded with traditional protection-deprotection protocols and ultrasound-mediated glycosylation reactions with other carbohydrate molecules to afford trimannosides in good yields. It is noteworthy that ultrasound-promoted reaction has worked well even at the last glycosylation step. Moreover, no cleavage of the glycoside bond during the oligomannoside synthesis was observed.

TEMPO-mediated Oxidation of Glucose or Sucrose under Ultrasound Irradiation

The same group cited above has developed a selective chemical oxidation reaction of the primary hydroxyl group of methyl α-D-glycoside to yield sodium (methyl α-D-glucopyranoside)uronate by employing sound wave energy. (J. Mol. Catal. A: Chem. 1999, 150, 31. DOI: 10.1016/S1381-1169(99)00197-1) They have obtained 63-76% yields, which depend on the probe diameter. They performed the reaction from 20 to 500 MHz or 0.008-0.26 (W/mL) acoustic power and around 5°C. They have used as reactants TEMPO (0.65 mol%), NaBr (0.4 equiv.), NaOCl (2.2 equiv.) and pH 10.5. Generally, a two-fold rate enhancement was observed in the sonochemical experiment when compared with the classical conditions. The authors have also observed that the presence of NaBr is not necessary for the reaction completion when employing ultrasound irradiation, whereas under silent conditions, such reagent is quite essential. Therefore, they have tried to rationalize the role of the sound-waves on this oxidation. As it is well known that ultrasound-irradiation promotes formation of radical species, they have proposed this occurs in the formation of the nitrosonium ion from TEMPO; thus enhancing the reaction rate. Later the same protocol was successfully employed in the oxidation of sucrose yielding the tricarboxylic acid in good yields.

Ultrasound-Ionic Liquid Promoted Acetylation of Sugars at Room Temperature

The acetylation of sugars has been achieved by using ionic liquid at room temperature in good yields (80-91%). When performed without ultrasound conditions, this reaction requires longer reaction times (120 min.) for complete conversion. The reaction proceeds without the addition of acid catalyst because of the acidic properties of the ionic liquid 1,3-di-n-butylimidazolium bromide ([bbim]Br). (Green Chem. 2003, 5, 693. DOI: 10.1039/b308069b)

Ultrasound/Lipase/Ionic Liquid-Promoted Synthesis of Sugar Esters

Ha and co-workers reported the enzyme-catalyzed esterification of sugars in ionic liquids (IL) under ultrasound irradiation. (Process Biochem. 2008, 43 1009. DOI: 10.1016/j.procbio.2008.05.001) In this green method, the lipase catalyzes the transesterification of glucose with vinyl laurate in the IL [Bmim][TfO] to afford 6-O-lauroyl-D-glucose. In general, the ultrasound-mediated reactions are 2.6 times faster than the ones performed under conventional conditions. It is noteworthy that the same reactions could also be done under the same ultrasound conditions by employing water and lauric acid. Thus, this cheaper protocol might attract interest from industries that are developing this kind of process.

Ultrasound Promoted Displacement of O-Trifyl by O-Acetyl

Fürstner and Konetzki have reported an efficient nucleophilic substitution of triflate by acetate groups in D-glucopyranose derivatives in the presence of n-Bu4NOAc and ultrasound energy (Tetrahedron Lett. 1998, 39, 5721. DOI: 10.1016/S0040-4039(98)01163-0) The importance of ultrasound in this reaction has been highlighted; because no product formation has been observed when the reaction is performed under silent conditions. Moreover, when the reaction was carried out for longer times under silent conditions, only decomposition of the starting materials took place.

R. A. W. N. Filho, R. N. de Oliveira, Org. Chem. Highlights 2009, July 25.