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Journal Name
Table 2. Synthesis of the azidosteroid 2 from 1b, at 65 °C
COMMUNICATION
the rotor and the stator, nano-droplets are generated.2
DOI: 10.1039/C8GC03923B
0
Entry
Stirring
speed
Reaction
time (min)
Conversion
(%)
It is important to emphasize that the Free Energy of
‡
‡
Activation (G ) for any reaction depends on its enthalpy (H )
(rpm)
‡
and TS thus involving the entropy of activation (G=H-
1
2
3
300
90
10
5
100
100
100
TS).21 When a reaction under traditional conditions is
6 000
8 000
‡
compared with a HSM reaction, the value of H remains
unchanged. In this context, the value of G depends on the S
(at constant temperature). So, to get a negative value of G (a
OH
OAc
OAc
O
spontaneous process) a bigger value of S is needed. A
significant difference in S is obtained when reactants are
constrained into a diminished volume and the collisions number
increase such as in the case of reactions assisted by HSM
technique.
Ac2O
Et3N, DMAP
O
H2NNH2 · AcOH
DMF
‡
HO
HO
O
AcO
AcO
AcO
AcO
OH
OAc
OH
OH
OAc
OAc
3
4
5
Scheme 2. Full protection and selective deprotection of glucose
The synthetic procedure using HSM is not limited to lab scale
if appropriated high shear mixers are used. For the above
described experiments, reactions using 0.1 to 10 g could be
launched using the IKA Ultra-Turrax T 18 digital mixer, but
more potent mixers are commercially available for
larger/industrial quantities. In all runs, micro/nano-droplets are
produced.
Both reactions were followed by H and 13C NMR. Table 3
shows the comparison of conversion times for the protection and
deprotection of glucose. When using HSM, the total formation
of 4 and 5 was afforded in 20 min at 10000 rpm, while under the
traditional stirring, longer reaction times were needed to reach
the total conversion in both reactions. Integration of the anomeric
proton signals allowed to monitor the reaction conversion. The
mixture of the and β anomers of 4 can be rapidly identified by
their typical doublet signals: 6.32 ppm, J1-2 = 3.7, ( anomer);
and 5.71 (J1-2 =8.3 Hz (β anomer). The anomeric carbon atoms
of 4 are shown at 89.2 ( anomer) and 91.8 ppm (β anomer). In
1
Conclusions
The use of HSM in common organic chemistry reactions has
shown to be beneficial since it involves high speed stirring,
which reduces reaction times. The reaction mixture is finely
shared producing a nano-droplets emulsion, minimizing the
mass transfer resistance and shifting the reaction equilibrium
towards the products. Results previously obtained in biodiesel
production and those obtained in this work reveals that this
technique can be considered as a potential alternative to improve
the development of different organic reactions due to its
considerable energy consumption decrease.
1
13
the H and C spectra of compound 5, the anomeric signals are
shifted upfields: 5.44 ppm ( anomer); and 4.74 (β anomer). The
anomeric carbon atoms of 5 are shown at 90.3 ( anomer) and
9
5.7 ppm (β anomer). The selective saponification of 4 was
followed by quantification of the integration of the anomeric
protons of 4 (full NMR spectra are available in the
Supplementary Information section).
Table 3. Protection and de-protection of glucose, at 25 °C
Entry
Compound
Stirring speed
rpm)
Reaction time
(min)
Conversion
(%)
(
Conflicts of interest
1
2
4
5
6
7
300
8 000
10 000
300
270
25
100
100
100
100
95
There are no conflicts to declare.
4
Acknowledgements
20
720
60
This manuscript was developed with the support of
CONACyT (Grants CB-254604, 254742, PN-2015-331 and
Scholarships to RZD and JCHM).
8 000
10 000
5
20
100
There are several factors that influence the reaction rates of Notes and references
chemical reactions such as temperature, concentration, physical
properties, pressure, solvent, catalyst, etc. All these factors are
related to collision theory18,19 which states that the more
collisions in a system occur, the higher reaction rate. A bigger
number of collisions among reactants occur into the small
volume of micro/nano-droplets, improving the reaction time. In
the HSM system, the material is subjected to very intense
shearing and thrusting forces due to the high acceleration forces.
In the existing shear gap between the rotor and the stator a large
turbulence additionally leads to an optimum mixture of the
1
2
3
4
P. T. Anastas and J. C. Warner, Green Chemistry, Theory and
Practice, Oxford University Press, New York, 1998, p.30
Warner, J.C.; Amy S. Cannon, A. S.; Dye, K. M., Environ.
Impact Assess. Rev., 2004, 24, 775.
Y. Ju, D. Kumar and R. S. Varma, J. Org. Chem., 2006, 71,
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697.
T, Imura, H. Yanagishita and D. J. Kitamoto, J. Am. Chem.
Soc., 2004, 126, 10804.
T. Bayer and K. Himmler, Chem. Eng. Technol. 2005, 28, 285.
J. S. Valente, M. Sánchez-Cantú, E. Lima, E., and F. Figueras,
Chem. Mater., 2009, 21, 5809.
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