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An improved sonochemical reactor
Ultrasonics Sonochemistry 12 (2005) 213–217 www.elsevier.com/locate/ultsonch
An improved sonochemical reactor Giancarlo Cravotto a
a,*
, Gabriele Omiccioli b, Livio Stevanato
a
Dipartimento di Scienza e Tecnologia del Farmaco, Universita di Torino, Via Giuria 9, Torino 10125, Italy b TEKIMP srl, Via Serenissima 20, Castelfranco Veneto (TV) 31033, Italy Received 1 September 2003; accepted 17 December 2003 Available online 6 March 2004
Abstract The design and optimization of sonochemical apparatus are still open to advancement. Under high-intensity ultrasound reaction rates and yields are mainly influenced by the characteristics of transducer and reactor. Several useful improvements are introduced and described. In order to achieve uniformity of the acoustic field and optimal acoustic streaming in every part of the reaction vessel (a Teflonâ tube), the reactor can be made to rotate eccentrically around the horn axis and the probe to move alternatively up and down by a pre-determined excursion at a chosen speed. Continuous high-power irradiation is feasible without any time limit because the whole probe system is refrigerated by an oil forced-circulation circuit connected to a chiller. The apparatus can control a number of important reaction parameters: modified atmosphere, reaction temperature, tunable frequency and constant amplitude. Excellent performance was observed on several reactions, such as the chemical modification of chitosan, a poorly soluble biopolymer. Ó 2004 Elsevier B.V. All rights reserved. Keywords: High-intensity ultrasound; Uniformity of irradiation; Improvements of sonochemical reactors; Chitosan; Reductive amination
1. Introduction Commercial ultrasonic emitters, though originally designed for different purposes, e.g. the cleaning of surfaces and the preparation of biological homogenates, also have notable chemical applications [1,2]. In the simplest models (cleaner baths), transducers are fixed to the underside of a tank, usually to be filled with water. The object to be sonicated, a reaction flask in particular, must be placed in the area of maximal irradiation, visualized by the strong rippling at the water surface. Because extra heat is produced, this is often removed by circulating a cold fluid through a coil placed in the bath, although a precise temperature control cannot be achieved in this way. Many unproductive reactions can thus be exploited. Higher irradiation intensities can be obtained using an immersion horn, in which case transducers are often cooled, usually by a fan. With this kind of setup physical parameters can be more easily controlled. Temperatures can be kept constant by *
Corresponding author. Tel.: +39-011-6707684; fax: +39-0116707687. E-mail address: [email protected] (G. Cravotto). 1350-4177/$ - see front matter Ó 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.ultsonch.2004.01.002
placing the reaction vessel in a thermostatted bath, or by circulating a cooling fluid through a double-walled reactor [3]. A basic parameter in ultrasonic engineering is power density, defined as the electrical power fed into the transducer divided by the radiating surface area. Transducers in current use for low-intensity systems (baths) have power densities of 1–2 W/cm2 at the transducer face. Higher powers are normally achieved by attaching several transducers to a single bath tank. Probe systems can deliver much greater power densities (several hundred W/cm2 ) at the radiating face of the horn. They can also reach much greater vibrational amplitudes [4]. Keeping in mind the theoretical studies published in the last three years [5–7] we have added a number of technical improvements to the design of sonochemical apparatus [8–10]. Our work as organic chemists required instruments capable of continuous operation at high intensities under stringent reaction conditions (modified atmosphere, controlled temperature etc.). In the following we shall then describe a novel cooling system for the transducer and a more efficiently thermostatted reactor. Because a uniform cavitation would further improve reaction rates and yields, we devised a mechanical means
214
G. Cravotto et al. / Ultrasonics Sonochemistry 12 (2005) 213–217
Fig. 1. Movements of reactor and probe.
by which a fairly homogeneous acoustic field is achieved (Fig. 1). As a demonstration we chose to carry out several sonochemical modifications of chitosan, a linear polysaccharide of 2-amino-2-deoxy-D-glucopyranose that is easily obtained by N-deacetylation of chitin. Chitosan and its derivatives are widely employed in many biomedical and pharmaceutical applications.
2. Experimental 2.1. Apparatus description The present instrument stems from the optimization of previously used models. Its transducer consists of highefficiency pre-stressed piezoelectric (PZT) rings (planar PZT Morgan Electronics, 50 mm in diameter) compressed between two erga discs. It is lodged in a Delrinâ housing cooled by oil that is pumped through it and is refrigerated by a chiller (800W). The transducer temperature, monitored by a thermocouple, is normally kept within 5–15 °C, and in no case allowed to reach 40 °C by the provision of a safety device. The bottom of the housing is cemented to the horn (machined from a highquality titanium alloy) whose shape represents a compromise between a stepped and an exponential taper; the tip diameter is 18 mm (Fig. 1). Frequency is tunable between 17 and 45 kHz and is shown on the display. In the present work we uniformly chose 18.2 kHz as standard operational frequency. Power can be varied up to a maximum of 1000 W, (corresponding to 390 W/cm2 at the horn tip) and is monitored by a true reading wattmeter. Reactions were carried out in a PTFE (Teflonâ ) tube (0.8 mm thick, 80 mm high, 35 mm in diameter) inserted in the Delrin housing with an interposed O-ring to make a hermetic seal. A thermostatting fluid (water-ethylene
glycol) is circulated through the intervening space and over four Peltier modules. Because Teflonâ has a low thermal conductivity, the reactor is best pre-cooled before sonication is started. The reactor can be made to rotate at 30 rpm around an axis whose distance from the horn axis can be manually regulated (max 10 mm). The linear speed of the up-and-down probe movement can also be regulated up to a maximum value of 1.2 mm/s. The excursion amplitude is accurately regulated by means of two photoelectric cells and is limited by a safety stop. When a modified reaction atmosphere is required, a Teflonâ gas inlet is inserted into the top of the reactor and joined to the horn by an elastomer sleeve coupling fixed to it with a tight seal (Figs. 2 and 3). It is also possible to bubble the gas (usually argon or nitrogen) through the reaction mixture. A patented electronic device [11] acting on the oscillating circuit continuously adjusts the US frequency to the actual resonance value of the reaction system (which is a function of irradiated volume, viscosity, nature of dissolved gases, surface tension and phase distribution of the mixture, etc.). This value is operationally defined as frequency that maximizes the US output for a given power setting. While the generator is designed for a maximum output of 1000 W, the maximum overall power consumption is 2200 W (also comprising chiller, Peltier cells, pumps etc.). The console has four digital displays: (1) the operating frequency (kHz); (2) the power fed to the transducer (up to 1000 W); (3) the transducer temperature (at 40 °C power is automatically cut off) and (4) the reactor temperature. The instrument is mounted on a movable bench. The overall dimensions are as follows: width 870 mm, depth 670 mm, height 1760 mm. Its weight is 230 kg. We used an hydrophone assembled by technicians of Galileo Ferraris Institute (Turin, Italy).
Fig. 2. Equipment for modified atmospheres.
G. Cravotto et al. / Ultrasonics Sonochemistry 12 (2005) 213–217
Under ordinary conditions substitution on chitosan and related biopolymers take place in a blockwise rather than in a uniform fashion, because large portions of the macromolecule are not accessible to the reagents. We achieved much higher values of the substitution index (SI ¼ percent of alkylated glucosamine units) because the expansion of the macromolecule under high-intensity ultrasound (HIU) exposes a greater number of reactive sites. Functionalization and protection of the amino group are the most common reactions [18,19] and many examples of reductive amination under conventional conditions (plain stirring) have been reported [20,21]. We obtained much better results (Scheme 1 and Table 1) when we compared reaction times and yields using a series of aldehydes, besides the PEG-acetaldehyde diethylacetal prepared according to Bentley [22] and a modified cyclodextrin (CD) bearing a formylethyl chain [23]. In the last case we used a monoformyl-b-CD, prepared by a procedure published by Hanessian [24]. To 10 ml of 4% chitosan solution (previously prepared by 20 min sonication of chitosan powder in H2 O/ CH3 COOH 99:1) 4 equiv/–NH2 of aldehyde dissolved in methanol were added. When the reaction was carried out under plain stirring, the aldehyde was dissolved in 5 ml of methanol; after 5 h, 5 equiv of NaCNBH3 were added portionwise. When the reaction was carried out under ultrasound, 2 ml methanol sufficed; 5 equiv of NaCNBH3 were added portionwise after 2 h when working with a standard probe system, after 1 h when working with the present apparatus.
Fig. 3. Teflonâ gas-inlet and elastomer sleeve coupling. The Teflonâ gas inlet, that fits tightly into the top of the reactor, is inserted into the wider end of an elastomer sleeve whose narrower end is slipped onto a Teflonâ ring that is fitted to the horn through the seal of an O-ring.
2.2. Reactions on chitosan Sonication is known to break the (1–4)-b-linkage, more rapidly at low pH values, because above pH 6.5 the amino groups are deprotonated and the polymer is insoluble. When prolonged, it can also promote the deacetylation of chitin [12,13]. Nevertheless under mild reaction conditions and in the presence of oxygen scavengers chain depolymerization does not occur [14]. While numerous applications of ultrasound have been published to physically modified chitosan (e.g. to favor its swelling and dissolution [15], to prepare polymeric vesicles [16,17] etc.) to the best of our knowledge no sonochemical modifications of this polysaccharide have been reported to-date.
H
CH2OH O H OH H
O
H O
H
R-CH2-CHO, MeOH
O
H2O, 1% AcOH H
H H
CH2OH O H OH H NH2
n
NaCNBH3
H
18.2 kHz,
NH2
215
CH2OH O H OH H
O
O
CH2OH O H OH H
O H
H
H H
350 W, 25°C
H
HN
n
NH2
R
Scheme 1. Reductive amination of chitosan.
Table 1 General procedure for reductive amination Entry
Aldehyde
Stirring 24 h b
1 2 3 4 5 6 7 8 9 10 a
HCHOc CH3 CHO CH3 CH2 CHO CH3 (CH2 )2 CHO (CH3 )2 CHCHO C6 H11 CHO C6 H5 CHO HOOC(CH2 )8 CHO PEG-acetal b-CD-CHO
Standard-type sonochemical reactora b
S.I.%
S.I.%
Time (h)
S.I.%b
Time (h)
42 25 20 18 20 24 21 – – –
60 38 33 30 32 40 24 – <5 10
5 5 6 6 6 6 7 7 7 7
86 82 75 73 70 64 40 18 22 28
3 3 3 3 3 3 3 4 4 4
Sonic Vibra Cell 600 apparatus at 20 kHz (nominal operating frequency) and 600 W. Substitution index determined by 1H NMR (Bruker 300 Advance). c Formaldehyde (37 w/w %). b
Improved apparatus
216
G. Cravotto et al. / Ultrasonics Sonochemistry 12 (2005) 213–217
4. Conclusion This paper describes several useful improvements added to a sonochemical apparatus of our construction, principally to achieve a better distribution of the irradiated energy. Its excellent performance, already reported in previous publications, has been demonstrated once more in the reductive amination of chitosan with a variety of aldehydes. Acknowledgements
Scheme 2. Sonochemical reactor: (1) transducer and booster, (2) horn, (3) reaction tube, (4) reactor eccentric rotation, (5) vertical probe excursion, (6) cooling oil (chiller), (7) thermostatting fluid (peltier cells).
The present work was supported by MIUR (Fondi ex-40%, project: ‘‘Addotti supra-molecolari tra b-ciclodestrine (e suoi multimeri) e complessi paramagnetici di Gd(III) per applicazioni diagnostiche mediante Risonanza Magnetica Imaging’’). References
3. Results and discussion The intensity of the acoustic field was evaluated by a hydrophone [25,26] placed in the reaction vessel at different depths and at a variable distance from the horn axis (the dimensions of the hydrophone must be very small with respect to ultrasound wavelength to avoid altering the acoustic field). Not unexpectedly, it was found to have a maximal value within 2–3 mm of the radiating surface, then to decline exponentially away from it [27]. The sound beam spread out in a truncated cone because of diffraction, reflection from the reactor wall and interference effects [3]. In order to make sonication as uniform as possible, the strong beam attenuation with vertical distance had to be compensated for. We achieved the purpose by combining two movements: the reactor rotates eccentrically around the horn axis while the horn moves alternatively up-and-down by a pre-determined excursion at a chosen speed (Scheme 2 and Fig. 1). The more efficient refrigeration systems provided for transducer and probe have made our instrument suitable for work at high intensities for a virtually unlimited time. Owing to the strict control of relevant parameters, chemical results proved highly reproducible. As a preliminary we repeated several reactions we had studied before in a more conventional sonochemical apparatus [28,29] at the same nominal power and almost the same frequencies. In all cases reaction times were considerably reduced and yields for heterogeneous-phase reactions improved; more notably, some reactions became feasible that could not be exploited using a standard-type sonicator (see Table 1). Several examples are given of sonochemical reductive amination of chitosan (Scheme 1), a poorly soluble biopolymer [30].
[1] T.J. Mason, J.P. Lorimer, Applied Sonochemistry, Wiley VCH, 2002. [2] J.L. Luche, Synthetic Organic Sonochemistry, Plenum Press, New York, 1998. [3] T.J. Mason, Practical Sonochemistry: Uses and Applications of Ultrasound, second ed., Horwood Publishing House, Chichester, 2002. [4] F.J. Keil, K.M. Swamy, Rev. Chem. Eng. 15 (1999) 85–155. [5] S.W. D€ahnke, F.J. Keil, Chem. Eng. Sci. 54 (1999) 2865–2872. [6] P.R. Gogate, A.B. Pandit, AIChE J. 46 (2000) 372–379. [7] C.L. Gong, D.P. Hart, J. Acoust. Soc. Am. 104 (1998) 2675–2682. [8] G. Cravotto, S. Chimichi, B. Robaldo, M. Boccalini, Tetrahedron Lett. 44 (2003) 8383–8386. [9] G. Cravotto, G.M. Nano, G. Palmisano, S. Tagliapietra, A. Demetri, A. Penoni, Eur. J. Org. Chem. 22 (2003) 4438–4444. [10] G. Cravotto, XXI Congresso Naz. S.C.I. Torino, Italy, 2003, Abs. OR-CO 019. [11] G. Cravotto, G. Omiccioli, E. Vazzoler, Patent PN 2003-A000032. [12] R.H. Chen, J.R. Chang, J.S. Shyur, Carbohydr. Res. 299 (1997) 287–294. [13] R.A.A. Muzzarelli, R. Rocchetti, Carbohydr. Polym. 5 (1985) 461–472. [14] R. Signini, J. Desbrieres, S.P. Campana Filho, Carbohydr. Polym. 43 (2000) 351–357. [15] D. Mislovicova, J. Masarova, K. Bendzalova, L. Soltes, E. Machova, Ultrason. Sonochem. 7 (2000) 63–68. [16] C. Dufes, A.G. Schatzlein, L. Tetley, A.I. Gray, D.G. Watson, J.C. Olivier, W. Couet, I.F. Uchegbu, Pharm. Res. 17 (2000) 1250–1258. [17] W. Wang, L. Tetley, I.F. Uchegbu, J. Colloid Interface Sci. 237 (2001) 200–207. [18] K. Kurita, Prog. Polym. Sci. 26 (2001) 1921–1971. [19] H. Sashiwa, Y. Shigemasa, Carbohydr. Polym. 39 (1999) 127–138. [20] M. Yalpani, L.D. Hall, Macromolecules 17 (1984) 272–276. [21] J. Desbrieres, C. Martinez, M. Rinaudo, Int. J. Biol. Macromol. 19 (1996) 21–28. [22] M.D. Bentley, M.J. Roberts, J.M. Harris, J. Pharm. Sci. 87 (1998) 1446–1449. [23] T. Tojima, H. Katsura, S.-M. Han, F. Tanida, N. Nishi, S. Tokura, N. Sakairi, J. Polym. Sci. A 36 (1998) 1965–1968. [24] S. Hanessian, A. Benalil, C. Laferriere, J. Org. Chem. 60 (1995) 4786–4792.
G. Cravotto et al. / Ultrasonics Sonochemistry 12 (2005) 213–217 [25] M.H. Entezari, P. Kruus, Ultrason. Sonochem. 3 (1996) 19–24. [26] R. Breeuwer, G. Blacquiere, Ultrason. Sonochem. 10 (2003) 197– 201. [27] P.R. Gogate, P.A. Tatake, P.M. Kanthale, A.B. Pandit, AIChE J. 48 (2002) 1542–1560.
217
[28] G. Cravotto, G.M. Nano, G. Palmisano, J. Carbohydr. Chem. 20 (2001) 495–501. [29] G. Cravotto, G.M. Nano, G. Palmisano, S. Tagliapietra, Synthesis 8 (2003) 1286–1291. [30] S. Tokura, N. Nishi, A. Tsutsumi, O. Somorin, Polym. J. 15 (1983) 485–489.
An improved sonochemical reactor Giancarlo Cravotto a
a,*
, Gabriele Omiccioli b, Livio Stevanato
a
Dipartimento di Scienza e Tecnologia del Farmaco, Universita di Torino, Via Giuria 9, Torino 10125, Italy b TEKIMP srl, Via Serenissima 20, Castelfranco Veneto (TV) 31033, Italy Received 1 September 2003; accepted 17 December 2003 Available online 6 March 2004
Abstract The design and optimization of sonochemical apparatus are still open to advancement. Under high-intensity ultrasound reaction rates and yields are mainly influenced by the characteristics of transducer and reactor. Several useful improvements are introduced and described. In order to achieve uniformity of the acoustic field and optimal acoustic streaming in every part of the reaction vessel (a Teflonâ tube), the reactor can be made to rotate eccentrically around the horn axis and the probe to move alternatively up and down by a pre-determined excursion at a chosen speed. Continuous high-power irradiation is feasible without any time limit because the whole probe system is refrigerated by an oil forced-circulation circuit connected to a chiller. The apparatus can control a number of important reaction parameters: modified atmosphere, reaction temperature, tunable frequency and constant amplitude. Excellent performance was observed on several reactions, such as the chemical modification of chitosan, a poorly soluble biopolymer. Ó 2004 Elsevier B.V. All rights reserved. Keywords: High-intensity ultrasound; Uniformity of irradiation; Improvements of sonochemical reactors; Chitosan; Reductive amination
1. Introduction Commercial ultrasonic emitters, though originally designed for different purposes, e.g. the cleaning of surfaces and the preparation of biological homogenates, also have notable chemical applications [1,2]. In the simplest models (cleaner baths), transducers are fixed to the underside of a tank, usually to be filled with water. The object to be sonicated, a reaction flask in particular, must be placed in the area of maximal irradiation, visualized by the strong rippling at the water surface. Because extra heat is produced, this is often removed by circulating a cold fluid through a coil placed in the bath, although a precise temperature control cannot be achieved in this way. Many unproductive reactions can thus be exploited. Higher irradiation intensities can be obtained using an immersion horn, in which case transducers are often cooled, usually by a fan. With this kind of setup physical parameters can be more easily controlled. Temperatures can be kept constant by *
Corresponding author. Tel.: +39-011-6707684; fax: +39-0116707687. E-mail address: [email protected] (G. Cravotto). 1350-4177/$ - see front matter Ó 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.ultsonch.2004.01.002
placing the reaction vessel in a thermostatted bath, or by circulating a cooling fluid through a double-walled reactor [3]. A basic parameter in ultrasonic engineering is power density, defined as the electrical power fed into the transducer divided by the radiating surface area. Transducers in current use for low-intensity systems (baths) have power densities of 1–2 W/cm2 at the transducer face. Higher powers are normally achieved by attaching several transducers to a single bath tank. Probe systems can deliver much greater power densities (several hundred W/cm2 ) at the radiating face of the horn. They can also reach much greater vibrational amplitudes [4]. Keeping in mind the theoretical studies published in the last three years [5–7] we have added a number of technical improvements to the design of sonochemical apparatus [8–10]. Our work as organic chemists required instruments capable of continuous operation at high intensities under stringent reaction conditions (modified atmosphere, controlled temperature etc.). In the following we shall then describe a novel cooling system for the transducer and a more efficiently thermostatted reactor. Because a uniform cavitation would further improve reaction rates and yields, we devised a mechanical means
214
G. Cravotto et al. / Ultrasonics Sonochemistry 12 (2005) 213–217
Fig. 1. Movements of reactor and probe.
by which a fairly homogeneous acoustic field is achieved (Fig. 1). As a demonstration we chose to carry out several sonochemical modifications of chitosan, a linear polysaccharide of 2-amino-2-deoxy-D-glucopyranose that is easily obtained by N-deacetylation of chitin. Chitosan and its derivatives are widely employed in many biomedical and pharmaceutical applications.
2. Experimental 2.1. Apparatus description The present instrument stems from the optimization of previously used models. Its transducer consists of highefficiency pre-stressed piezoelectric (PZT) rings (planar PZT Morgan Electronics, 50 mm in diameter) compressed between two erga discs. It is lodged in a Delrinâ housing cooled by oil that is pumped through it and is refrigerated by a chiller (800W). The transducer temperature, monitored by a thermocouple, is normally kept within 5–15 °C, and in no case allowed to reach 40 °C by the provision of a safety device. The bottom of the housing is cemented to the horn (machined from a highquality titanium alloy) whose shape represents a compromise between a stepped and an exponential taper; the tip diameter is 18 mm (Fig. 1). Frequency is tunable between 17 and 45 kHz and is shown on the display. In the present work we uniformly chose 18.2 kHz as standard operational frequency. Power can be varied up to a maximum of 1000 W, (corresponding to 390 W/cm2 at the horn tip) and is monitored by a true reading wattmeter. Reactions were carried out in a PTFE (Teflonâ ) tube (0.8 mm thick, 80 mm high, 35 mm in diameter) inserted in the Delrin housing with an interposed O-ring to make a hermetic seal. A thermostatting fluid (water-ethylene
glycol) is circulated through the intervening space and over four Peltier modules. Because Teflonâ has a low thermal conductivity, the reactor is best pre-cooled before sonication is started. The reactor can be made to rotate at 30 rpm around an axis whose distance from the horn axis can be manually regulated (max 10 mm). The linear speed of the up-and-down probe movement can also be regulated up to a maximum value of 1.2 mm/s. The excursion amplitude is accurately regulated by means of two photoelectric cells and is limited by a safety stop. When a modified reaction atmosphere is required, a Teflonâ gas inlet is inserted into the top of the reactor and joined to the horn by an elastomer sleeve coupling fixed to it with a tight seal (Figs. 2 and 3). It is also possible to bubble the gas (usually argon or nitrogen) through the reaction mixture. A patented electronic device [11] acting on the oscillating circuit continuously adjusts the US frequency to the actual resonance value of the reaction system (which is a function of irradiated volume, viscosity, nature of dissolved gases, surface tension and phase distribution of the mixture, etc.). This value is operationally defined as frequency that maximizes the US output for a given power setting. While the generator is designed for a maximum output of 1000 W, the maximum overall power consumption is 2200 W (also comprising chiller, Peltier cells, pumps etc.). The console has four digital displays: (1) the operating frequency (kHz); (2) the power fed to the transducer (up to 1000 W); (3) the transducer temperature (at 40 °C power is automatically cut off) and (4) the reactor temperature. The instrument is mounted on a movable bench. The overall dimensions are as follows: width 870 mm, depth 670 mm, height 1760 mm. Its weight is 230 kg. We used an hydrophone assembled by technicians of Galileo Ferraris Institute (Turin, Italy).
Fig. 2. Equipment for modified atmospheres.
G. Cravotto et al. / Ultrasonics Sonochemistry 12 (2005) 213–217
Under ordinary conditions substitution on chitosan and related biopolymers take place in a blockwise rather than in a uniform fashion, because large portions of the macromolecule are not accessible to the reagents. We achieved much higher values of the substitution index (SI ¼ percent of alkylated glucosamine units) because the expansion of the macromolecule under high-intensity ultrasound (HIU) exposes a greater number of reactive sites. Functionalization and protection of the amino group are the most common reactions [18,19] and many examples of reductive amination under conventional conditions (plain stirring) have been reported [20,21]. We obtained much better results (Scheme 1 and Table 1) when we compared reaction times and yields using a series of aldehydes, besides the PEG-acetaldehyde diethylacetal prepared according to Bentley [22] and a modified cyclodextrin (CD) bearing a formylethyl chain [23]. In the last case we used a monoformyl-b-CD, prepared by a procedure published by Hanessian [24]. To 10 ml of 4% chitosan solution (previously prepared by 20 min sonication of chitosan powder in H2 O/ CH3 COOH 99:1) 4 equiv/–NH2 of aldehyde dissolved in methanol were added. When the reaction was carried out under plain stirring, the aldehyde was dissolved in 5 ml of methanol; after 5 h, 5 equiv of NaCNBH3 were added portionwise. When the reaction was carried out under ultrasound, 2 ml methanol sufficed; 5 equiv of NaCNBH3 were added portionwise after 2 h when working with a standard probe system, after 1 h when working with the present apparatus.
Fig. 3. Teflonâ gas-inlet and elastomer sleeve coupling. The Teflonâ gas inlet, that fits tightly into the top of the reactor, is inserted into the wider end of an elastomer sleeve whose narrower end is slipped onto a Teflonâ ring that is fitted to the horn through the seal of an O-ring.
2.2. Reactions on chitosan Sonication is known to break the (1–4)-b-linkage, more rapidly at low pH values, because above pH 6.5 the amino groups are deprotonated and the polymer is insoluble. When prolonged, it can also promote the deacetylation of chitin [12,13]. Nevertheless under mild reaction conditions and in the presence of oxygen scavengers chain depolymerization does not occur [14]. While numerous applications of ultrasound have been published to physically modified chitosan (e.g. to favor its swelling and dissolution [15], to prepare polymeric vesicles [16,17] etc.) to the best of our knowledge no sonochemical modifications of this polysaccharide have been reported to-date.
H
CH2OH O H OH H
O
H O
H
R-CH2-CHO, MeOH
O
H2O, 1% AcOH H
H H
CH2OH O H OH H NH2
n
NaCNBH3
H
18.2 kHz,
NH2
215
CH2OH O H OH H
O
O
CH2OH O H OH H
O H
H
H H
350 W, 25°C
H
HN
n
NH2
R
Scheme 1. Reductive amination of chitosan.
Table 1 General procedure for reductive amination Entry
Aldehyde
Stirring 24 h b
1 2 3 4 5 6 7 8 9 10 a
HCHOc CH3 CHO CH3 CH2 CHO CH3 (CH2 )2 CHO (CH3 )2 CHCHO C6 H11 CHO C6 H5 CHO HOOC(CH2 )8 CHO PEG-acetal b-CD-CHO
Standard-type sonochemical reactora b
S.I.%
S.I.%
Time (h)
S.I.%b
Time (h)
42 25 20 18 20 24 21 – – –
60 38 33 30 32 40 24 – <5 10
5 5 6 6 6 6 7 7 7 7
86 82 75 73 70 64 40 18 22 28
3 3 3 3 3 3 3 4 4 4
Sonic Vibra Cell 600 apparatus at 20 kHz (nominal operating frequency) and 600 W. Substitution index determined by 1H NMR (Bruker 300 Advance). c Formaldehyde (37 w/w %). b
Improved apparatus
216
G. Cravotto et al. / Ultrasonics Sonochemistry 12 (2005) 213–217
4. Conclusion This paper describes several useful improvements added to a sonochemical apparatus of our construction, principally to achieve a better distribution of the irradiated energy. Its excellent performance, already reported in previous publications, has been demonstrated once more in the reductive amination of chitosan with a variety of aldehydes. Acknowledgements
Scheme 2. Sonochemical reactor: (1) transducer and booster, (2) horn, (3) reaction tube, (4) reactor eccentric rotation, (5) vertical probe excursion, (6) cooling oil (chiller), (7) thermostatting fluid (peltier cells).
The present work was supported by MIUR (Fondi ex-40%, project: ‘‘Addotti supra-molecolari tra b-ciclodestrine (e suoi multimeri) e complessi paramagnetici di Gd(III) per applicazioni diagnostiche mediante Risonanza Magnetica Imaging’’). References
3. Results and discussion The intensity of the acoustic field was evaluated by a hydrophone [25,26] placed in the reaction vessel at different depths and at a variable distance from the horn axis (the dimensions of the hydrophone must be very small with respect to ultrasound wavelength to avoid altering the acoustic field). Not unexpectedly, it was found to have a maximal value within 2–3 mm of the radiating surface, then to decline exponentially away from it [27]. The sound beam spread out in a truncated cone because of diffraction, reflection from the reactor wall and interference effects [3]. In order to make sonication as uniform as possible, the strong beam attenuation with vertical distance had to be compensated for. We achieved the purpose by combining two movements: the reactor rotates eccentrically around the horn axis while the horn moves alternatively up-and-down by a pre-determined excursion at a chosen speed (Scheme 2 and Fig. 1). The more efficient refrigeration systems provided for transducer and probe have made our instrument suitable for work at high intensities for a virtually unlimited time. Owing to the strict control of relevant parameters, chemical results proved highly reproducible. As a preliminary we repeated several reactions we had studied before in a more conventional sonochemical apparatus [28,29] at the same nominal power and almost the same frequencies. In all cases reaction times were considerably reduced and yields for heterogeneous-phase reactions improved; more notably, some reactions became feasible that could not be exploited using a standard-type sonicator (see Table 1). Several examples are given of sonochemical reductive amination of chitosan (Scheme 1), a poorly soluble biopolymer [30].
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