Supporting information for
Azide/Alkyne-"Click"-Reactions on Amino-Resins-Materials: an
LC-ESI-TOF Analysis
Haitham Barqawi and Wolfgang H. Binder*
Institute of Chemistry, Division of Technical and Macromolecular Chemistry, Chair of
Macromolecular Chemistry, Martin-Luther Universität Halle-Wittenberg, D-06120 Halle
(Saale), Germany.
Captions for Figures/Tables
Figure S1.
Inversed gate decoupling of 13C NMR spectra of (a) the unmodified melamine
formaldehyde resin (MF neat) and (a) the alkyne-terminated melamine
formaldehyde resin.
Figure S2.
GPC- traces of neat MF resin and those modified ones with different amounts
of propargyl alcohol (0-86.3 mmol)
Figure S3.
IR spectrum of monomer TD (4), showing the presence of the azide band at
2019 cm-1.
Figure S4.
1
H NMR spectrum of (azidomethyl) benzene (2).
Figure S5.
1
H NMR spectrum of n-octyl azide (1).
Figure S6.
1
H NMR spectrum of 1-(6-azidohexyl)thymine (3).
Table S1
Alkyne/azide “click”-reaction using 0.085 mmol of Cu(I)Br and 7.74 of
DIPEA as base in methanol at 70 °C for 24 h, the MF bearing benzyl moieties
(BA, 2) were fully characterized.
Table S2
Alkyne/azide “click”-reaction using 0.028 mmol of Cu(I)Br and 10.99 mmol of
DIPEA as base in methanol at 70 °C for 12 h, the MF bearing octyl moieties
(OA, 1) were fully characterized.
Synthesis of (azidomethyl) benzene (2)
The general synthesis is described in literature.1
The azide derivative was synthesized by adding benzylbromide onto a 0.5 M solution of NaN3
in DMSO. The reaction mixture was stirred at 40 °C for 48 h. The reaction was controlled by
TLC for completion and subsequently water was added to the mixture. The latter was
extracted with ether three times, and the ether phase was washed with water and brine. The
product was dried over Na2SO4. Yield: 2.52 g (92.2 %). 1H-NMR (400 MHz, CDCl3, δ, ppm):
7.42 -7.33 (m, 5H, Ar-H), 4.35 (s, 2H, Ar-CH2-N3).
1-(6-azidohexyl)-5-methylpyrimidine-2,4(1H,3H)-dione (3)
The general synthesis is described in literature.2
1-(6-bromohexyl)-5-methylpyrimidine-2,4(1H,3H)-dione (1.5 g, 5.2 mmol) and sodium azide
(0.41g, 6.2 mmol) were refluxed in acetonitrile for 18 h. Consequently, the solid was filtered
and the solution was concentrated to a gum, which slowly crystallized. The material was
recrystallized from water. Yield 1.1 g (83 %). 1H-NMR provided in Figure S5.
Synthesis of 4-azidobenzoic acid (4a)
The general synthesis is described in literature.3
To a suspension of 4-aminobenzoic acid (4.5 g, 33 mmol) in water (25 mL) in a 2 L-round
bottom flask was added concentrated HCl (5.6 mL) drop wise while the mixture was
vigorously stirred. After the addition has been finished the reaction mixture was cooled down
to 0 °C with an ice-salt-mixture. A solution of NaNO2 (2.3 g, 33 mmol) in water (10 mL) was
added slowly (about 30 min) via dropping funnel. The color of the mixture changes to yelloworange during the addition. Subsequently, a solution of NaN3 (2.14 g, 33 mmol) in water (25
mL) was added slowly whilst the mixture was vigorously stirred, whereby an enormous foam
formation could be observed. The cooling bath was removed and stirring was continued for
90 min and afterwards a 100 mL water and 125 mL ethylacetate were added. The phases were
separated via a separating funnel and the water phase was extracted with 50 mL ethylacetate
twice. The organic phase was washed with 1 N NaOH (40 mL). The water phase was
acidified with 1 N HCl (80 mL), whereby a yellow solid precipitates. During the acidification
ethylacetate (150 mL) was added in portions, which solves the yellow solid. The organic
phase was separated and the unified organic phases were then dried over Na2SO4, filtered and
concentrated via vacuum distillation at room temperature to furnish a yellow solid. Yield:
4.98 g (92 %). 1H-NMR (400 MHz, CDCl3, δ, ppm): 8.11, (d, 2H, 3J = 8.62 Hz), 7.11 (d, 2H,
3
J = 8.63 Hz)
13
C-NMR (100 MHz, CDCl3, δ, ppm): 145.8, 132.2, 125.7, 119.1. IR: 2813,
2541, 2101, 1672, 1600, 1577, 1507, 1424, 1316, 1282, 1177, 1138, 1122, 934, 856, 765
Synthesis of 4-azidobezoylchloride (4b)
The synthesis was accomplished according to literature with minor changes.4
4-Azidobenzoic acid (1 g, 6.13 mmol) was added to fresh distilled thionylchloride (22.2 mL,
306 mmol) and refluxed for 4 h at 75 °C. When the reaction has finished the excess of
thionylchloride was removed under vacuum. The achieved brown solid was dried using high
vacuum. Yield: 1.1 g (99 %). IR: 3098, 2401, 2252, 2119, 1737, 1594, 1498, 1417, 1306,
1282, 1208, 1171, 1121, 876, 837, 815, 804, 726, 696, 642.
Figure S1. Inversed gate decoupling of 13C NMR spectra of (a) the unmodified melamine
formaldehyde resin (MF neat) and (b) the alkyne-terminated melamine
formaldehyde resin.
Figure S2. GPC- traces of neat MF resin and those modified ones with different amounts of
propargyl alcohol (0-86.3 mmol)
Figure S3. IR spectrum of monomer TD (4), showing the presence of the azide band at 2109
cm-1
Figure S4. 1H NMR spectrum of (azidomethyl) benzene (2)
Figure S5. 1H NMR spectrum of n-octyl azide (1)
Figure S6. 1H NMR spectrum of 1-(6-azidohexyl)thymine (3)
Table S1. Alkyne/azide “click”-reaction using 0.085 mmol of Cu(I)Br and 7.74 of DIPEA as
base in methanol at 70 °C for 24 h, the MF bearing benzyl moieties (BA, 2) were
fully characterized.
Structure
Formula
Compounds
RT (min)
HPLC
m/z
m/z
(observed)
(simulated)
ESI-MS-TOF
Ionized
Error (ppm)
Species
1
2
C14H17N9O
C16H21N9O2
MBA
MFMeBA
19.2
21.7
328.161
372.186
328.163
372.189
5.790
8.598
M+H
M+H
3
C18H25N9O3
MF2Me2BA
24.1
416.210
416.215
12.734
M+H
4
5
C20H29N9O4
C25H28N12O2
MF3Me3BA
MBA2
27.2
28
460.239
529.250
460.242
529.253
5.866
5.479
M+H
M+H
6
C26H30N12O3
MFBA2
27.7
559.262
559.264
3.934
M+H
8
C28H34N12O4
MF2MeBA2
26.7
620.296
620.316
33.692
M+H
9
C27H32N12O3
MF2MeBA3
29.6
573.279
573.282
5.407
M+H
10
C33H44N12O7
MF5Me3BA2
21.5
743.374
743.335
-52.601
M+Na
11
C31H38N18O4
MF2MeBA5
21.5
756.364
756.296
-89.912
M+K
Table S2. Alkyne/azide “click”-reaction using 0.028 mmol of Cu(I)Br and 10.99 mmol of
DIPEA as base in methanol at 70 °C for 12 h, the MF bearing octyl moieties (OA,
1) were fully characterized.
HPLC
Entry
Formula
1
C15H27N9O
2
Compounds
MOA1
rt (min)
ESI-MS-TOF
m/z (observed) m/z (simulated)
error (ppm)
Ionized
Species
15.2
388.197
388.263
170.5
M+H
C16H29N9O2 MFMe2OA1
20.2
402.234
402.254
51.7
M+Na
3
4
5
C17H31N9O3 MF1Me2OA1
C20H37N9O6 MF2Me2OA1
C19H35N9O5 MOA1
23.4
45.6
432.244
416.262
460.289
432.293
416.249
460.276
113.1
-29.8
-28.2
M+Na
M+Na
M+K
6
C25H47N9O7 MF4OA1
25.1
608.349
608.400
83.8
M+Na
8
C21H39N9O5 MF3Me3OA2
30.1
515.341
515.290
-99.9
M+NH4
9
C18H33N9O3 MF2Me2OA3
26.8
424.278
424.190
-206.5
M+H
References
(1)
(2)
(3)
(4)
Alvarez, S. G.; Alvarez, M. T. Synthesis 1997, 1997, 413-414.
Summers, W. A.; Lee, J. Y.; Burr, J. G. J. Org. Chem. 1975, 40, 1559-1561.
Wetzels, G. M. R.; Koole, L. H. Biomaterials 1999, 20, 1879-1887.
Borda, E. J.; Sigurdsson, S. T. Nucl. Acids Res. 2005, 33, 1058-1068.