triazole derivatives as pharmaceutical crystallization media ...High thermal stability, pH...
Transcript of triazole derivatives as pharmaceutical crystallization media ...High thermal stability, pH...
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High thermal stability, pH responsive organogels of 2H-benzo[d]1,2,3-triazole derivatives as pharmaceutical crystallization media.
Iván Torres-Moyaa,b, Basanta Saikiac, Pilar Prietob*, José R. Carrillob, Jonathan W. Steeda*
a Department of Chemistry, Durham University, South Road, Durham, DH1 3LE, UK.
b Department of Organic Chemistry. University of Castilla La Mancha, 13071 Ciudad Real, Spain.
c Department of Chemical Sciences, Tezpur University, Napaam-784028, Assam, India.
Contents:
1. Synthetic schemes2. Gelation tests.3. SEM Images4. Rheology experiments.5. Unit cell determination
Electronic Supplementary Material (ESI) for CrystEngComm.This journal is © The Royal Society of Chemistry 2018
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1. Synthetic schemes
Br
C12H25OOC12H25
OC12H25
+
SiMe3C12H25O
OC12H25
OC12H25
SiMe3
K2CO3
MeOH/THFC12H25O
OC12H25
OC12H25
9 10 113a
Scheme S1. Synthesis of the alkynyl derivative 3a.
BrO
NH2
BrO
NHC12H25
Br-C12H25
TBAB/KOH
O
NHC12H25
SiO
NH
K2CO3
MeOH/THFC12H25
SiMe3
12 13
143c
Scheme S2. Synthesis of the alkynyl derivative 3c.
NH2
+
C12H25OOC12H25
OC12H25
EDCDMAP
CH2Cl260ºC NH
OOC12H25
OC12H25OC12H25
O OH
15 6
3d
Scheme S3. Synthesis of the alkynyl derivative 3d.
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2. Gelation tests
(S= Soluble, I= Insoluble, P= Precipitate, PG= Partial Gel, G= Gel)
Table S1. Gelation test for 4a at a concentration of 2% wt.
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Table S2. Gelation test for 4a at a concentration of 1% wt.
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Table S3. Gelation test for 4a at a concentration of 0.5% wt.
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Table S4. Gelation test for 4b at a concentration of 2% wt.
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Table S5. Gelation test for 4b at a concentration of 1% wt.
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Table S6. Gelation test for 4b at a concentration of 0.5% wt.
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Table S7. Gelation test for 4c at a concentration of 2% wt.
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Table S8. Gelation test for 4c at a concentration of 1% wt.
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Table S9. Gelation test for 4c at a concentration of 0.5% wt.
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Table S10. Gelation test for 4d at a concentration of 2% wt.
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Table S11. Gelation test for 4d at a concentration of 1% wt.
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Table S12. Gelation test for 4d at a concentration of 0.5% wt.
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Table S13. Gelation test for 4e at a concentration of 2% wt.
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Table S14. Gelation test for 4e at a concentration of 1% wt.
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Table S15. Gelation test for 4e at a concentration of 0.5% wt.
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Figure S1. Gels for 4a at 1% wt in (from left to right) 1-pentanol and 1,4-butanediol.
Figure S2. Gels for 4e at 2% wt in (from left to right) in DMF, Ethanol, Methanol, 1-butanol and 1-propanol.
Figure S3. Gels for 4e at 0.5% wt in (from left to right) in Ethanol, 1-butanol, 1-propanol, 2-butanol, 2-propanol and 1,4-butanediol.
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3. SEM Images
Figure S4. SEM images for compound 4a.
Figure S5. SEM images for compound 4c.
Figure S6. SEM images for compound 4d.
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4. Rheology experiments
Figure S7. Frequency sweep for 4a at 2% wt in 1,4-butanediol.
Figure S8. Stress sweep for 4a at 2% wt in different solvents.
2% wt 2-propanol= 63 Pa
2% wt Methanol= 1259 Pa
2% wt 1,4-butanediol= 914 Pa
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Figure S9. Stress sweep for 4d at 2% wt in different solvents.
Figure S10. Stress sweep for 4e at 2% wt in different solvents.
2% wt Diethylene glycol= 40 Pa
2% wt Methanol = 25 Pa
2% wt DMF = 631 Pa
2% wt 1-butanol = 1585 Pa
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Figure S11. Comparison of the Stress sweep rheology in ethanol for 4e at different concentrations.
10 100 1000
100
1000
10000
G'/G
"osc. stress (Pa)
G' G"
2% wt Ethanol = 501 Pa
10 100 1000
10
100
1000
G'/G
"
osc. stress (Pa)
G' G"
1% wt Ethanol = 100 Pa
10 100 1000
100
1000
10000
G'/G
"
osc. stress (Pa)
G' G"
0.5% wt Ethanol = 63 Pa
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5. Unit cell determination
Figure S12. Unit cell determination for crystallization of sulfathiazole in absence of the gel (left) or in presence of the gel (right).
a= 8.156(2) b= 8.480(2) c= 15.406 (4)V=1062.7(7)
Monoclinic P
Polymorph II
a= 8.8478 (4)b= 13.352 (6)c= 14.1584 (6)V= 1480.77
Orthorombic C
Polymorph I
pO