Solvent-free sonochemistry: Sonochemical organic synthesis in the absence of a liquid medium

Article abstract of DOI:10.3762/bjoc.13.179

Sonochemistry, i.e., the application of mechanical energy in the form of sound waves, has recently been recognised for its similarity to mechanochemistry and is now included under the umbrella term of mechanochemistry. Typically, due to the hypothesised c

Full text of DOI:10.3762/bjoc.13.179

Solvent-free sonochemistry: Sonochemical organic synthesis
in the absence of a liquid medium
Deborah E. Crawford
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2017, 13, 1850–1856.
School of Chemistry and Chemical Engineering, Queen’s University
Belfast, David Keir Building, 39–123 Stranmillis Road, Belfast, BT9
doi:10.3762/bjoc.13.179
5AG, Northern Ireland, UK
Received: 15 May 2017
Accepted: 18 August 2017
Published: 04 September 2017
Email:
Deborah E. Crawford - d.crawford@qub.ac.uk
This article is part of the Thematic Series "Mechanochemistry".
Guest Editor: J. G. Hernández
Keywords:
mechanochemistry; organic; solvent-free; sonochemistry; synthesis
©
2017 Crawford; licensee Beilstein-Institut.
License and terms: see end of document.
Abstract
Sonochemistry, i.e., the application of mechanical energy in the form of sound waves, has recently been recognised for its simi-
larity to mechanochemistry and is now included under the umbrella term of mechanochemistry. Typically, due to the hypothesised
cavitation mechanism, a liquid medium is considered as a necessity for a process to take place as a result of ultrasonic irradiation. In
view of this, condensation reactions between solid reagents in the complete absence of solvent were carried out successfully by
ultrasonic irradiation with the importance of particle size being highlighted. This work increases the potential of sonochemistry in
the drive towards a sustainable future.
Introduction
Mechanochemistry is typically regarded as the grinding of solid Sonochemistry is hypothesised to originate from acoustic cavi-
reagents in a ball mill (or mortar and pestle), to instigate tation and bubble collapse as a result of the mechanical effects
and accelerate chemical reactions [1]. In recent years, of sounds on liquids [8,9]. Bubble collapse in particular results
mechanochemistry has evolved to include techniques such as in intense compressional heating, thereby creating hot spots, a
shearing [2], microfluidics [3] and twin screw extrusion [4-6]. phenomenon currently employed to explain the processes
More recently, sonochemistry has been included under the occurring in ball milling [7]. It must also be noted that there is a
umbrella term of mechanochemistry [7] as it has demonstrated similar technology available to sonochemistry, that is consid-
excellent potential when instigating chemical activity in solu- ered to be less harsh than mechanochemistry, and this is reso-
tions by applying mechanical energy (Figure 1) [8,9].
nant acoustic mixing (RAM). The RAM mixes by controlling
1850

Beilstein J. Org. Chem. 2017, 13, 1850–1856.
Figure 1: Typical laboratory employed planetary ball mill and ultrasonic bath.
the vibration applied to the material through acceleration and The Knoevenagel condensation [18], Michael addition [19] and
frequency, and therefore is actually mechanistically different Biginelli reactions [20] amongst others have been instigated by
from sonochemical mixing [8,9]. Other effects that have ultrasonic irradiation in the presence of solvents such as pyri-
been found to be common for both sonochemistry and dine and methanol, resulting in a decrease of their reaction
mechanochemistry include: local heating, crystal deformation times from >10 hours to 1–2 hours. Also, in some cases
and phase transitions amongst others [7].
sonication greatly improved the yield, for example in a
Vilsmeier–Haack reaction [21]; in addition selectivity can also
Ultrasonic irradiation is commonly carried out on liquid/gas be improved as demonstrated in a Pinacol coupling whereby a
mixtures (for gas removal), liquid/liquid mixtures and liquid/ meso-isomer was the dominant product, a result only observed
solid mixtures. The technique is used extensively in materials when the reaction is sonicated [22].
chemistry, for example, it has been demonstrated to be one of
the most efficient methods to exfoliate layered materials such as Results and Discussion
graphite (to form graphene) [10], but it has also been employed The presence of a liquid medium in a system undergoing ultra-
in the formation of organometallic [11] and organic compounds sonic irradiation is greatly important to facilitate the cavitation
[
12]. Great success has been found in the treatment of waste process and a consequence of this is that there has not been any
water by ultrasonic irradiation, to remove heavy metals or research into sonochemical reactions being carried out in the
degrade aromatic constituents [13].
absence of solvent, or a liquid reagent [8,9]. Herein, we report
two condensation reactions (investigated extensively by ball
Metal catalysts are prepared by the sonication of metal halides milling), one to form salen ligand 1 by sonicating o-vanillin and
e.g., Pt and Pd – reduction of metal) in the presence of Li and 1,2-phenylenediamine, and the second to form 1,3-indandione 2
(
THF [14,15]. Furthermore, the catalytic behaviour of catalysts from ninhydrin and dimedone. Both systems were investigated
such as Raney Nickel, has reportedly been increased solely due in the complete absence of solvent and without the presence of
to the effect of using ultrasound [16]. Catalyst coatings, such as any grinding media (such as inert silica beads) to help mediate
metal oxide, can be broken up and removed as a result of ultra- the reaction. The aldol reaction was successfully carried out by
sonic cavitation, therefore this technology overcomes the draw- twin screw extrusion, as I have reported previously [6]. The
backs of reacting a solid and a liquid in a heterogeneous system, success of both of these reactions by ultrasound irradiation in
allowing the reaction to proceed further [16].
the absence of solvent creates potential for organic synthesis to
be carried out by applying a milder form of mechanical energy,
The reaction of toluene with benzyl bromide in the presence of i.e., sound waves. As a result, it may be possible that reactions
KCN/Al2O3, is an example of organic synthesis employing which are particularly sensitive to intense mechanical energy
ultrasound [17]. Interestingly, the conventional solution method (and may undergo degradation) may be successful by ultra-
results in the alkylation of the toluene aromatic ring, however, sonic irradiation.
when sonication is employed, a reaction between benzyl bro-
mide and KCN occurs producing PhCH2CN, indicating that al- It must be noted that the conventional reaction between
ternative products can be formed using this technique, as with o-vanillin and 1,2-phenylenediamine requires refluxing for
ball milling.
9 hours in ethanol for a complete conversion to the product. For
1851

Beilstein J. Org. Chem. 2017, 13, 1850–1856.
the initial sonochemistry experiments (Scheme 1), both reagents Stopping the reaction to grind this solid form into a free flowing
were used as received, o-vanillin came in the form of small solid would lead to inaccurate results as mechanical energy in
flakes and 1,2-phenylenediamine was received as large crys- the form of grinding could have a significant effect on the
talline beads (Figure 2).
outcome of the reaction. Therefore, as the application of heat
may have an effect on the conversion to product and the mix-
Upon sonication of the mixed reagents (using a standard ultra- ture needed to remain as a free slowing solid, sonication was
sonication bath with a frequency of 35 kHz) for 60 minutes, it carried out for 10 minute intervals, preventing an increase in
was observed that the temperature of the ultrasonic bath in- temperature and melting of the reagents (alternatively a cooling
creased to 70–75 °C, causing both reagents to form a melt fluid could be used). After 60 minutes of sonicating, a colour
(
o-vanillin has a melting point of 42 °C, 1,2-phenylenediamine change was observed (Figure 3 – to bright orange) but there was
has a melting point of 104 °C), which is likely to be the result of a clear separation between the two solids, indicating that the
an eutectic melt forming. This was quite surprising as the variation of particle size and morphology was too great for the
melting point of 1,2-phenylenediamine is greater than that of reaction to proceed quantitatively.
the observed temperature of the ultrasonic bath. The molten
substance then changed to a hard solid form and not the Therefore, both reagents were ground and sieved to both be fine
preferred free flowing solid. It was expected that because the powders of particle size <500 µm. A ca. 0.2 g mixture was soni-
reagents melted then they would have reacted completely to cated for 60 minutes (keeping the temperature of the bath at
form the product, aided by the help of heating. However, ambient temperature) and it was clear to see that a more suc-
1
H NMR spectroscopy showed that the conversion to the prod- cessful reaction had taken place. A homogeneous orange solid
uct was only 36%, therefore, the reaction did not proceed signif- was produced; however, there was an increase in the pressure of
icantly as a result of the high temperature, and the reaction was the system that was too great to be withheld in the 2 mL vial
potentially hindered as a result of the hard solid formed.
employed. This was presumably due to the production of the
Scheme 1: Reaction between o-vanillin and 1,2-phenylenediamine by ultrasonic irradiation for 60 minutes.
Figure 2: o-Vanillin in its flake form and 1,2-phenylenediamine in its bead form.
1852

Beilstein J. Org. Chem. 2017, 13, 1850–1856.
Figure 3: Clear separation of the reagents observed, with orange coated beads of 1,2-phenylenediamine residing at the bottom of the mixture.
byproduct – water, which was seen to be in its vapour form,
most likely due to the heat produced from the exothermic reac-
tion of the aldehyde and the diamine. This indicated that a
greater free volume (also known as ‘headspace’) in the vial was
required to accommodate this increase in pressure.
A larger vial (25 mL) was then employed, which was able to
sustain the pressure of the water vapour produced in the system,
and with that there was a 5-fold scale-up of the reaction mix-
Figure 4: Chemical structures of the products obtained from the reac-
tion between o-vanillin and 1,2-phenylenediamine.
ture from ca. 0.2 g to ca. 1.0 g. After 60 minutes of ultrasonic
irradiation a bright orange free flowing solid was produced indi-
cating that a reaction had occurred. 1H NMR spectroscopy
showed that indeed a reaction had taken place to form the cated for 60 minutes, resulting in a dark red powder (Figure 5).
desired imine; however, a conversion to product of only 69% 1H NMR spectroscopy showed that the reaction had fully con-
was determined. The experiment was repeated but ultrasonic ir- verted to the desired product – the desired diimine, 1 (Figure 6).
radiation was carried out for 90 minutes, leading to a margin- Powder X-ray diffraction (PXRD) analysis shows that the
ally higher conversion to product of 73%.
powder patterns of both the sonochemical product and the solu-
In order to improve the rate of conversion to product, a mild
base, anhydrous Na2CO3 (0.1 equiv) was added to the reaction.
o-Vanillin, 1,2-phenylenediamine and Na2CO3 were then soni-
cated for 60 minutes to produce a dark red solid (similar to that
obtained from solution). 1H NMR spectroscopy indicated that
the reagents had almost all been consumed; however, it was
noted that the 1H NMR spectrum was more complicated than
expected with two peaks representing imine protons. It was de-
termined that the desired product had formed along with the
product from the 1:1 reaction of the aldehyde and the diamine,
1
’ (Figure 4). Excess aldehyde was expected to be present;
however, this was not the case (<1% present), indicating that
the reaction mixture was still not completely homogeneous.
In order to overcome this problem, the particle size of both
starting materials was reduced further to <200 µm and soni-
Figure 5: Reaction mixture before and after ultrasonic irradiation for 60
minutes.
1853

Beilstein J. Org. Chem. 2017, 13, 1850–1856.
Figure 6: 1H NMR spectrum of diimine 1 in CDCl3/EtOD.
tion product are the same and IR spectroscopy confirmed that CDCl3 to ensure that the reactions were not proceeding as a
an imine bond was present in the product, with no indication of result of exposure to the NMR spectroscopy solvent, which was
an aldehyde functionality being present (see Supporting Infor- found to be the case. Therefore, it is ultrasonic irradiation at
mation File 1).
room temperature that is instigating and accelerating this chemi-
cal reaction.
Sonochemical reactions are reportedly irreproducible [11] and
to determine if this was the case in the reaction between Further confirmation that sonochemistry is a viable method to
o-vanillin and 1,2-phenylenediamine, the experiment was carry out solid state organic synthesis was obtained by carrying
repeated under the optimised conditions three times. In each out an aldol reaction between ninhydrin and dimedone
case, the reaction was reproducible showing a complete conver- (Scheme 2). The optimised parameters from the previous
sion to the product (as determined by 1H NMR spectroscopy). system were applied, i.e., the particle size of the reagents was
In addition, a control reaction was carried out whereby the reduced (to <200 µm) and ultrasonic irradiation was carried out
reagents (in the same concentrations) were mixed manually and in 10 minute intervals to prevent melting of the reagents. After
left for several days without being agitated. Although there was 90 minutes of sonicating, a pink solid was produced with
some colour change in the mixture, the reaction had not 1H NMR spectroscopy indicating that a complete reaction had
proceeded significantly (after 3 days, <5% conversion to prod- taken place between a hydroxy group of ninhydrin and the acti-
uct was observed). Furthermore, the reaction was monitored in vated methylene of dimedone (Figure 7). This reaction has pre-
Scheme 2: Aldol reaction between ninhydrin and dimedone to form 2.
1854

Beilstein J. Org. Chem. 2017, 13, 1850–1856.
Figure 7: 1H NMR spectrum of 1,3-indandione 2 in DMSO-d6.
viously been carried out by twin screw extrusion in the absence of sonochemical reactions, therefore aiding in the drive towards
of solvent [6], and it was confirmed that the same product was sustainable chemistry.
obtained by both synthetic methods (see Supporting Informa-
tion File 1). A control experiment was carried out, whereby the
Supporting Information
reagents were mixed as two solids and left under ambient tem-
perature and pressure for several weeks, after three weeks, a
Supporting Information File 1
conversion of 72% to the desired product was observed,
confirming the advantage of employing sonochemistry.
Experimental part.
http://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-13-179-S1.pdf]
[
Conclusion
In conclusion, the first examples of ultrasound induced solvent-
free condensation reactions are reported, forming a Schiff base Acknowledgements
(which has significant applications in catalysis) and a 1,3- I would like to thank the EPSRC for funding (EP/L019655/1)
1
indandione 2. It was concluded that one of the key parameters and Professor Stuart L. James of the Queen’s University Belfast
in these reactions was the particle size of the starting materials, for all of his help and advice.
with a reduced particle size of <200 µm resulting in a homoge-
neous mixture leading to complete conversion to the product. References
This provides an excellent foundation for further investigations
into solvent-free or solid-state sonochemistry, including
studying a larger scope of chemical reactions and the mecha-
nism behind which the liquid/solvent-free reactions occur. It
also provides a means of applying a gentler form of mechanical
energy to a system which may increase the range of organic and
inorganic mechanochemical transformations that can be carried
out (where grinding results in degradation of the material).
Finally, as with ball milling, there is potential for the scale-up
1. James, S. L.; Adams, C. J.; Bolm, C.; Braga, D.; Collier, P.; Friščić, T.;
Grepioni, F.; Harris, K. D. M.; Hyett, G.; Jones, W.; Krebs, A.; Mack, J.;
Maini, L.; Orpen, A. G.; Parkin, I. P.; Shearouse, W. C.; Steed, J. W.;
Waddelli, D. C. Chem. Soc. Rev. 2012, 41, 413–447.
doi:10.1039/C1CS15171A
2
.
Kaupp, G. CrystEngComm 2009, 11, 388–403. doi:10.1039/B810822F
3. Rivas, D. F.; Cintas, P.; Gardeniers, H. J. G. E. Chem. Commun. 2012,
8, 10935–10947. doi:10.1039/c2cc33920j
4
1855

Beilstein J. Org. Chem. 2017, 13, 1850–1856.
4.
Crawford, D. E.; Casaban, J.; Haydon, R.; Giri, N.; McNally, T.;
James, S. L. Chem. Sci. 2015, 6, 1645–1649.
doi:10.1039/C4SC03217A
License and Terms
5
.
.
Crawford, D. E.; Wright, L. A.; James, S. L.; Abbott, A. P.
Chem. Commun. 2016, 52, 4215–4218. doi:10.1039/C5CC09685E
Crawford, D. E.; Miskimmin, C. K. G.; Albadarin, A. B.; Walker, G.;
James, S. L. Green Chem. 2017, 19, 1507–1518.
doi:10.1039/C6GC03413F
This is an Open Access article under the terms of the
Creative Commons Attribution License
6
(http://creativecommons.org/licenses/by/4.0), which
permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
7.
8.
9.
Suslick, K. S. Faraday Discuss. 2014, 170, 411–422.
doi:10.1039/C4FD00148F
Margulis, M. A. Ultrason. Sonochem. 1994, 1, S87–S90.
doi:10.1016/1350-4177(94)90003-5
The license is subject to the Beilstein Journal of Organic
Chemistry terms and conditions:
Tanaka, R.; Takahashi, N.; Nakamura, Y.; Hattori, Y.; Ashizawa, K.;
Otsuka, M. RSC Adv. 2016, 6, 87049–87057.
doi:10.1039/C6RA16209F
(http://www.beilstein-journals.org/bjoc)
The definitive version of this article is the electronic one
which can be found at:
1
1
1
1
0.Notley, S. M. Langmuir 2012, 28, 14110–14113.
doi:10.1021/la302750e
1.Suslick, K. S. Adv. Organomet. Chem. 1986, 25, 73–119.
doi:10.1016/S0065-3055(08)60573-0
doi:10.3762/bjoc.13.179
2.Li, J.-T.; Wang, S.-X.; Chen, G.-F.; Li, T.-S. Curr. Org. Synth. 2005, 2,
415–436. doi:10.2174/1570179054368509
3.Jamali, M. K.; Kazi, T. G.; Arain, M. B.; Afridi, H. I.; Jalbani, N.;
Memon, A. R. J. Agron. Crop Sci. 2007, 193, 218–228.
doi:10.1111/j.1439-037X.2007.00261.x
14.Wen-Chou, L.; Maltsev, A. N.; Kobosev, N. I. Russ. J. Phys. Chem.
1964, 38, 41–46.
1
5.Maltsev, A. N. Russ. J. Phys. Chem. 1976, 50, 995–998.
6.Kowalska, E.; Dziegielewska, M. Ultrasonics 1976, 14, 73–75.
doi:10.1016/0041-624X(76)90102-5
1
1
1
1
2
7.Doan, T. L. H.; Le, T. N. Synth. Commun. 2012, 42, 337–340.
doi:10.1080/00397911.2010.524338
8.Li, J.-T.; Li, T.-S.; Li, L.-J.; Cheng, X. Ultrason. Sonochem. 1999, 6,
1
99–201. doi:10.1016/S1350-4177(99)00014-0
9.Li, J.-T.; Cui, Y.; Chen, G.-F.; Cheng, Z.-L.; Li, T.-S. Synth. Commun.
003, 33, 353–359. doi:10.1081/SCC-120015762
2
0.Yadav, J. S.; Reddy, B. V. S.; Reddy, K. B.; Raj, K. R.; Prasad, A. R.
J. Chem. Soc., Perkin Trans. 1 2001, 1939–1941.
doi:10.1039/b102565c
2
1.Ali, M. M.; Sana, S.; Tasneem; Rajanna, K. C.; Saiprakash, P. K.
Synth. Commun. 2002, 32, 1351–1356. doi:10.1081/SCC-120003631
2.Rieke, R. D.; Kim, S.-H. J. Org. Chem. 1998, 63, 5235–5239.
doi:10.1021/jo971942y
2
1856