A series of new Schiff bases derived from 2-aminopyridenes and various aromatic aldehydes have been synthesized and thoroughly investigated by 1H and 13C NMR spectroscopy. The imines were found to exist as only a single E-isomer at ambient temperature. Interestingly, 1H- and 13C-NMR chemical shifts of the (CH=N) amino group are affected by the type of substituent group (X) on the aryl ring. Furthermore UV and IR Spectra of some of the title compounds are also reported.
Schiff bases appear to be an important intermediate in a number of enzymatic reactions involving interaction of an enzyme with an amino or a carbonyl group of the substrate. One of the most important types of catalytic me- chanism is the biochemical process which involves the condensation of a primary amine in an enzyme usually that of a lysine residue, with a carbonyl group of the substrate to form an imine, or Schiff base. Many studies have been carried out on various rings such as triazoles, pyrazoles, oxadiazoles, and imidazoles to develop new antibacterial agents. In view of these reports, the synthesis of a new series of substituted 2-aminopyridine deriv- atives is reported here since pyridine derivatives continue to attract great interest due to the wide variety of in- teresting biological activities observed in these compounds, such as anticancer, analgesic, antimicrobial, and an- tidepressant, activities [
2-Aaminopyridine and its substituents andbenzaldehyde and its substituents were procured from Lancaster Syn- thesis Ltd and were used without any further purification.
IR spectra were measured using Nexus, 470-670-760 spectrophotometer FT IR, spectrometer spectrum 8400 s, using KBr pellets for solid compounds and neat liquid compounds between KBr plates. NMR spectra were measured at 24˚C on a Jeol 400 MHz spectrometer using deuterium locking 13C(1H)-NMR observation frequen- cy 100 MHz, 1H-NMR,observation frequencies, 400 MHz.
The Schiff bases were prepared by mixing equivalent amounts of substituted aryl aldehydes and 2-aminopyri- dine derivatives in 80 ml. methanol. This mixture was boiled under reflux with stirring for 9 h at 80˚C in an oil bath, and then concentrated by rotary evaporation to give yellow liquid. This was treated with n-hexane to pre- cipitate the crude product, which was recrystallized in dichloromethane and with n-hexane to give yellow preci- pitate, dried. Yield 70% - 90%, (Scheme 1,
The microanalytical data and m.pts. Data are listed in
1H-NMR (400 MHz, CDCl3, δ ppm), compound 1, 7.31 (H-3-arom.), 7.24 (H-4, arom.), H-5 (7.81, arom., H-6 (8.49, arom.), H-3' (7.43, arom.), H-4' (7.34 arom.), H-5' (6.69, arom.), H-6' (7.58, arom.), -OH (13.48), HC=N (9.44); compound 2, H-5 (6.60, arom.), H-6 (8.04, arom.), H-2' (7.30, arom.), H-6' (6.82, arom.), -OH (12.60), HC=N (9.15); compound 3, H-5 (6.71, arom.), H-6 (8.45, arom.), H-3' (6.28, arom.), H-4' (7.93, arom.), H-5' (6.16, arom.), -OH (12.37), HC=CN (9.42); compound 4, H-5 (6.62, arom.), H-6 (8.54), H-2' (7.50, arom.), H-3'
Scheme 1. Synthesis of Schiff bases.
. Schiff bases compounds
Compound No. | X | Y | Compound No. | X | Y |
---|---|---|---|---|---|
1 | 2-OH | H | 8 | 4-NO2 | 4-Me |
2 | H | 3-Me | 9 | 4-Br | 4-Me |
3 | 2-OH | 3-Me | 10 | H | 5-Cl |
4 | 4-NO2 | 3-Me | 11 | 2-OH | 5-Cl |
5 | 4-Br | 3-Me | 12 | 4-NO2 | 5-Cl |
6 | H | 4-Me | 13 | 4-Br | 5-Cl |
7 | 2-OH | 4-Me |
. Microanalytical data and M.P. data for the synthesized Schiff bases
No. | X | M.p. (˚C) | M.F. | Calculated (%) | Found (%) | ||||
---|---|---|---|---|---|---|---|---|---|
C | H | N | C | H | N | ||||
1 | 2-OH | 73 | C12H10N2O | 72.71 | 5.08 | 14.13 | 72.38 | 4.98 | 14.05 |
2 | H | 88 | C13H12N2O | 79.56 | 6.16 | 14.27 | 77.98 | 6.31 | 13.64 |
3 | 2-OH | 110 | C13H12N2O | 73.56 | 5.69 | 13.19 | 73.63 | 5.82 | 13.34 |
4 | 4-NO2 | 130 | C13H11N3O2 | 64.72 | 5.59 | 17.41 | 64.35 | 3.91 | 16.55 |
5 | 4-Br | 77 | C13H11BrN2 | 57.15 | 4.02 | 10.18 | 57.43 | 4.13 | 9.81 |
6 | H | 84 | C13H12N2 | 79.56 | 6.16 | 14.27 | 78.28 | 6.31 | 17.64 |
7 | 2-OH | 100 | C13H12N2O | 73.56 | 5.69 | 13.19 | 73.63 | 5.82 | 13.34 |
8 | 4-NO2 | 140 | C13H11N3O2 | 64.72 | 5.59 | 17.41 | 64.35 | 3.91 | 15.55 |
9 | 4-Br | 98 | C13H11BrN2 | 57.15 | 4.02 | 10.18 | 57.43 | 4.13 | 12.81 |
10 | H | 106 | C12H9CIN2 | 66.51 | 4.15 | 12.93 | 65.68 | 4.13 | 12.32 |
11 | 2-OH | 94 | C12H9CIN2O | 61.93 | 3.87 | 12.01 | 61.84 | 3.78 | 12.12 |
12 | 4-NO2 | 203 | C12H8CIN3O2 | 55.06 | 3.05 | 16.06 | 55.80 | 3.04 | 15.89 |
13 | 4-Br | 180 | C12H8BrCIN2 | 48.74 | 2.70 | 9.47 | 47.31 | 2.51 | 10.67 |
(7.71, arom.), H-5' (7.71, arom.), H-6' (7.5, arom.), -OH (12.55), HC=N (9.25); compound 5, H-5 (6.60, arom.), H-6 (8.45), H-2' (7.50, arom.), H-3' (6.81, arom.), H-5' (6.81, arom.), H-6' (7.5, arom.), -OH (12.50), HC=N (9.25); compound 6, H-6 (8.34), H-2' (7.80, arom.), H-6' (7.00, arom.), HC=N (9.15); compound 7, H-3 (6.80, arom.), H-6 (7.67), H-2' (6.96, arom.), H-6' (6.94, arom.), -OH (13.59), HC=N (9.43); compound 8, H-3 (6.80, arom.), H-6 (8.80), H-2' (7.50, arom.), H-6' (6.33, arom.), HC=N (9.26); compound 9, H-3 (6.80, arom.), H-6 (8.35), H-2' (7.80, arom.), H-6' (7.03, arom.), HC=N (9.11); compound 10, H-3 (7.48, arom.), H-4 (7.35, arom.) H-6 (8.42), H-1' (7.93, arom.), H-6' (7.27, arom.), HC=N (9.12); compound 11, H-3 (7.51, arom.), H-4 (7.10, arom.), H-6 (8.45), H-1' (7.76, arom.), H-6’(6.95 arom.), HC=N (9.41), -OH (13.24); compound 12, H-3 (8.14, arom.), H-4 (8.12, arom.) H-6 (8.44), H-1' (8.32, arom.), H-6' (7.30, arom.), HC=N (9.26); compound 13, H-3 (7.26, arom.), H-4 (7.84, arom.) H-6 (8.42), H-1' (7.26, arom.), H-6' (7.84, arom.), HC=N (9.08); 13C-NMR (400 MHz, CDCl3, δ ppm), compound 1, C-2 (155.20), C-3 (119.50), C-4 (138.80), C-5 (123.40), C-6 (149.20), C-1' (118.20), C-2' (161.20), C-3' (119.20), C-4' (133.40), C-5' (118.10), C-6' (132.90), C=N (163.50); compound 6, C-4 (138.00), C-1' (135.00), C-2' (129.26), C-3' (128.58), C-4' (131.69), C-5' (128.58), C-6' (129.260), -CH3 (20.97); compound 7, C-2 (156.69), C-3 (121.98), C-4 (138.37), C-5 (121.98), C-6 (157.88), C-1' (118.93), C-2' (161.62), C-3' (117.09), C-4' (133.22), C-5' (118.87), C-6' (133.45), C=N (164.15), -CH3 (24.38); compound 8, C-2 (159.16), C-3 (125.49), C-4 (137.00), C-5 (125.49), C-6 (149.20), C-1' (137.16), C-2' (129.33), C-3' (134.40), C-4' (148.05), C-5' (134.40), C-6' (129.33), C=N (159.39), -CH3 (20.93); compound 9, C-2 (148.33), C-3 (134.01), C-4 (136.56), C-5 (134.01), C-6 (149.39), C-1' (134.67), C-2' (130.57), C-3' (131.88), C-4' (120.56), C-5' (131.88), C-6' (130.87), C=N (161.13), -CH3 (20.97); compound 10, C-2 (159.39), C-3 (120.85), C-4 (137.51), C-5 (137.58), C-6 (157.07), C-1' (137.88), C-2' (129.88), C-3' (132.26), C-4' (129.66), C-5' (132.26), C-6' (128.90), C=N (163.46); compound 11, C-2 (161.59), C-3 (133.45), C-4 (137.96), C-5 (130.24), C-6 (147.57), C-1' (121.60), C-2' (155.64), C-3' (117.14), C-4' (133.99), C-5' (119.22), C-6' (133.45), C=N (164.97); compound 12, C-1 (158.47), C-2 (131.00), C-4 (138.04), C-5 (130.14), C-6 (149.85), C-1' (141.14), C-2' (130.98), C-3' (124.08), C-4' (147.85), C-5' (124.04), C-6' (130.18), C=N (160.52); compound 13, C-2 (158.95), C-3 (134.64), C-4 (137.95), C-5 (130.13), C-6 (147.41), C-1' (137.958), C-2' (132.23), C-3' (130.94), C-4' (121.09), C-5' (130.94), C-6' (132.23), C=N (162.00).
In the present work, the new 2-(X-benzylidine)-Y-pyridins (Schiff’s bases) were obtained from the reaction of X-benzaldehydes with 2-amino-Y-pyridines. The products were solids and the yields were 70% - 90%, reasona- bly high which indicates greater reactivity of these carbonyl compounds.
The stereochemistry of the free imines was determined on the basis of their 1H and 13C-NMR spectral data. The 1H-NMR spectrum (in CDCl3), shows that there is only one set of isomer signals, exist mainly in E-imine form.
The infrared spectra show that the absorption of the C=N group for imines 1 - 13 (
The IR results are in good agreement with an earlier study of some imines derived from some thiophene and furfural derivatives which have been reported to exist exclusively in the E-form [
IR spectrum of compound (9), shows (C=C-H), for aromatic ring, stretching frequency, abdsorbed at 3039.81 cm−1, v 2964.59 cm−1, and CH3 stretching vibration appear at v 2864.59 cm−1. These results are in agreement with published results [
The 1H NMR spectra of imines having CH3-substituents (imines, 1 - 9) in pyridine ring, the CH3 and =C-H groups of this imines appear as a single peak at δ (2.37 - 2.60) ppm for CH3 groups, and at δ (9.01 - 9.43) ppm as a single peak for C-H protons. These results indicate that only one diasterioisomeris present in the solution for these imines.
The 1H-NMR spectra of imines (7) has been chosen as a model in order to simplify the NMR spectra. In CDCl3 solution, the Ar-CH3 group resonates at δ 2.59 ppm (single peak) and -OH group resonates at δ 13.59 ppm (single peak). The H-C= Proton resonate at δ 9.43 ppm (single peak). The aromatic protons appear as (ABA’B’) pattern. The pyridine proton, H6 of imine (7) resonate at δ 7.67 ppm (doublet of doublet) at low field, and so the H3 and H5, and due to the absorption of pyridine protons and aromatic ring protons absorb in the same region, a complicated and observed as an overlap spectra.
The 13C-NMR spectra of imine (7) has been chosen model in order to simplify the 13C-NMR spectra. The qu- aternary carbon in pyridine and aromatic rings and imine group C=N, are readily identified since they are less intense compared with other signals as a result of long relaxation times of the quaternary carbons [
Further evidence comes from imine spectrum of compound (13). The proton NMR spectrum shows signal at δ 9.08 ppm (single peak) for 1H-C=N proton, and another signal at δ 8.42 ppm assigned for C6-H. The 1H-NMR signals C3-H, C4-H (on pyridine ring) and aromatic protons signals shown at δ 7.26 - 7.84 ppm together. But the case will be different by studying the 13C-NMR of imine (13). The numbers of 13C are 10 carbons. The quater- nary carbon is less intense compared with other carbon signals. The assignments of the chemical shifts of the backbone carbons are based either on spin-lattice relaxation or on the study of substituent effects in benzene de- rivatives [
The 13C chemical shifts of imines are listed in the experimental part. It is worth noting that the carbon −13 chemical shifts for isomethine group (imines) (HC=N) carbons are affected by both (X) and (Y) substituent’s on aromatic and pyridine rings respectively. When (X)-NO2 group substituted at C-4, the C=N, singleresonance
. δ 1H-CH=N and δ 13C=N for Schiff bases (1 - 13)
Complex No. | δ 13C=N (ppm) | δ 1H-CH=N (ppm) | Complex No. | δ 13C=N (ppm) | δ 1H-CH=N (ppm) |
---|---|---|---|---|---|
1 | 163.50 | 9.44 | 8 | 159.39 | 9.26 |
2 | 164.11 | 9.15 | 9 | 161.13 | 9.11 |
3 | 146.24 | 9.42 | 10 | 163.46 | 9.12 |
4 | 159.25 | 9.25 | 11 | 164.97 | 9.41 |
5 | 161.02 | 9.01 | 12 | 160.52 | 9.26 |
6 | 164.65 | 9.15 | 13 | 162.00 | 9.08 |
7 | 164.15 | 9.43 |
appear at δ 159.39 ppm, the more electron withdrawing group, the more shielding effect. The substitution at py- ridine ring shows less effect on δ C=N absorption (
The new pyridine imines derivatives have been characterized by elemental analysis, UV, IR, 1H, and 13C-NMR spectroscopy. Interestingly, the carbon-13 chemical shifts for azomethine group (imines) (CH=N) carbons which are affected by both (X) and (Y) substituents. The stereochemistry of the imines was determined through their NMR spectral data. The imines were found to exist in solution as only a single E-isomer at ambient temperature.
The authors would like to thank the Research Center, College of Science, Princess Nora University and King Abdulaziz city for Science and Technology for the financial support to this Research Project (AT-17-171).