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Scientific paper
Tautomerism of Allyl-5-(pyridin-2-yl)-[1,3,4] Thiadiazol-2-yl) Amine
Leokadia Strzemecka
Chair and Department of Organic Chemistry, Faculty of Pharmacy with Medical Analytics Division, Medical University of Lublin, Staszica 6, 20 - 081 Lublin, Poland
* Corresponding author: E-mail: leokadia.strzemecka@am.lublin.pl
Received: 15-06-2007
Abstract
The radical and ionic structures of allyl-(5-pyridin-2-yl-[1,3,4] thiadiazol-2-yl )-amine 1A O 1A' O 1A'a, 1A (I) O 1A (I)' O 1A (I)'a have been determined by means of its 1H (100 MHz, 500 MHz) 13C and 15N NMR spectra and B3LYP/6-31G** computations. The tautomeric intercorvertions of 1A 01A (I ) ^ 1B, 1A 01A (I ) ^ 1C have been observed in the 1H NMR spectra (100 MHz)
Keywords: Allyl-(5-pyridin-2-yl-[1,3,4]-thiadiazol-2-yl)-amine; tautomerism
1. Introduction
The 13C 15N NMR studies of allyl- (1) and (3-phenyl-allyl)- (2) (5-(pyridin-2-yl)-[1,3,4] thiadiazol-2-yl)-amine and theoretical calculations support ionic and radical structures (Figs 1-4)1. The XRD data support only one tautomer a - type in the crystals of both compounds 1, 2. In the solid state the exo-amino form a is stabilized by different H bonds, and the differences in the total energy between tautomers a and b are equal to -35.6
and -34.3 kJ/mol for 1 and 2, respectively, according to DFT level of theory calculations1. The 1H- data (100 MHz, 500 MHz), 13C-and 15N NMR spectra as well as the theoretical calculations of allyl-(1) and (3-phenyl-allyl)-(2) (5-pyridin-2-yl-[1,3,4] thiadiazol-2-yl)-amine (tauto-mer a - type) point to the changes of the amine - type a nitrogen atom N-6 to pyridine - type A and pyrrole - type A (I) of 1, 2 and to sp hybridization A (II) of 2. In the range of the chemical shifts of the NH proton from 5 8.665 to 7.233, the 1H NMR (100 MHz) spectra of 1, 2 there are no
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10 ,N
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\ H
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ii
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H
V
tf/ =N
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8/
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R =
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(2)
Fig. 1. The tautomers a and b of allyl- 1 and (3-phenyl-allyl)-2 (5-(pyridin-2-yl)-[1,3,4] thiadiazol-2-yl)-amine with atom numbering.
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H
H	H
\7 8/
II

10
W—N

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\ H
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/9
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Fig. 2. The tautomers a' and b' c' of allyl- 1 and (3-phenyl-allyl)-2 (5-(pyridin-2-yl)-[1,3,4] thiadiazol-2-yl)-amine with atom numbering.
Fig. 3. The resonance structures of allyl-1 and (3-phenyl-allyl)-2 (5-pyridin-2-yl)-[1,3,4]thiadiazol-2-yl)-amine.
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¿5^
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transitions of electrons of p orbitals of 1S 2C 3N 4N 5C of 1,3,4-thiadiazole ring. The nitrogen atoms N3, N4, N10 appear as pyridine - type, pyrrole - type and amine - type. Due to the changes of the electronic structure of these atoms the radical structures are possible (Fig. 3). The changes of the electronic structure of the nitrogen atoms N3, N4, N10 have been described previously 2.
Previous 100 MHz 1H NMR investigations of 1, 2 in the solution in the range from 5 8.665 to 7.233 of the chemical shift of N-H proton support the tautomeric equilibrium between allyl - (1) (3-phenyl-allyl-) (2) (5-pyridin-2-yl-[1,3,4] thiadiazol-2-yl-) amine 1A 1A', 2A (I) 2A (I)', 2A (II) 2A (II)', 3H allyl- (1) (3-phenyl-allyl-) (2) (5-pyridin-2-yl-[1,3,4] thiadiazol-2-ylidene-) amine 1B 1B', 2B 2B' 2B (II)' and 4H allyl- (1) (3-phenyl-allyl-) (2) (5-pyridin-2-yl-[1,3,4] thiadiazol-2-ylidene-) amine 1C', 2C' 2C (II)'2- 3.
In the 1H NMR spectra 100 MHz of 1, 2 the signals of NH proton in the range of the chemical shifts from 5 8.665 to 7.233 point to the co - existence of two tautomeric forms 1A' ^ 1B', 1A' ^ 1C', 2A(I)' ^ 2B', 2A(II)' ^ 2C(II)'. In the 1H NMR spectra 100 MHz of 1 the intensities of the signals of N-H proton confirm the intercon-vertions of the 1A'5 ^ 1B3 ^ 1C'4 as well as the balance of 1A'7 ^ 1B'7 and 1A'7 ^ 1C'7 tautomers and support pyridine - type nitrogen atoms N-10 N-4 N-6 and the amine - type nitrogen atoms N-4 N-3 of 1,3,4 - thiadiazole ring2, respectively. In the 1H NMR spectra of 2 (100MHz) the interconvertions of 2A(I)'1-4 ^ 2B' 14 2A(II)'1-4 ^
2C(II)', 2A(I)'
6, 7
2B' 7, 2A(II)'6
2C(II)'
6, 7
tautomers have been observed and support the amine -type nitrogen atoms N4, N3 of 1,3,4 - thiadiazole ring3.
The aim of the present paper was to describe the electronic structure of the nitrogen atoms of 1a tautomer
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Fig. 4. The resonance structures of the pyridyl substituent.
in the range from 5 7.125-6.500 of the chemical shifts of the N-H proton and its interconvertions to the imino forms in the solution.
The structural studies of the 2-amino-[1,3,4]thiadia-zole derivatives have been performed in order to know the properties of the compounds with the determined biological activity. The N6 and/or 5-substituted-2-amino 1, 3, 4-thiadiazoles depending on the nature of substituents show varied pharmacological activity. They have revealed potent activity against the leukemia, melanoma, lung carcinoma. They are also known to be the carbonic anhydrase inhibitors, and some of them possess the antimycobacte-rial, anesthetic, antidepressant and anxiolytic activity4-14. The 2-amino-[1,3,4]thiadiazoles are found in a new class of herbicides with a broad spectrum of activity15 as well as the corrosion inhibitors16.
2. Experimental
The product 1 was prepared according to the published method 17 and its NMR spectra (1H, 13C, 15N) were recorded under various conditions: on Tesla BS 677 A and Bruker AM 500 spectrometers.
The 1H-, 13C- and 15N-NMR measurements of 1 were taken in CDCl3 and in DMSO - d6 solutions, respectively on a Bruker AM 500 spectrometer, operating at 500.18 MHz for hydrogen, 125.76 MHz for carbon and 50.68 MHz for nitrogen, using standard conditions. The 2D spectra of 1H-13C HMQC, 1H-13C HMBC, 1H-1H COSY (500 MHz) have been recorded in a CDCl3 solution according to procedure given in the Bruker programme library. The 1H-NMR spectra (1-6) of 1 were measured on a Tesla BS 677 A spectrometer (100 MHz with T.F.) in CDCl3 or DMSO solutions at room temperature with TMS as the internal standard. The 1H-NMR spectra 1, 13 14, 2-6, 65, 66 (100 MHz) and 17 (500 MHz) have been recorded in CDCl3 solution and the spectra 11 12 (100 MHz) in DMSO so3ution17, 18, 1. The 1H- NMR spectra 11-4 (100 MHz) 18 have been taken using various concentration of 1 in DMSO or CDCl3 solutions:
-	in a DMSO solution, the concentration of 1 amounts to 1:3 (spectra 11 12, respectively);
-	in a CDCl3 solution, the concentration of 1 amounts to: 10 mg/0.5 ml and 25 mg/0.5 ml (maximal concentration, spectra 1314, respectively).
The 1H-N!VIR spectra 1-6, 65 6617, 171 and 1818 have been recorded in CDCl3 and DMSO - D2O solutions, respectively, without any determination of the concentration of 1. In the 1H-NMR spectra 1-6 of 1 the signals of the protons of allyl, pyridyl substituents as well as of NH proton of 1,3,4-thiadiazole have been recorded. In the 1H-NMR spectra 65 66 of 117 only the signals of the NH proton of the 1,3,4-thiadiazole have been recorded.
The molecular geometries and properties corresponding to the local minima of the energy were calculated1 at the DFT level of the theory with the B3LYP density functional and the 6-31G** basis set19, 20. The same basis set and functional were used for the 1H-, 13C- and 15N-NMR shielding constants calculations by applying the GIAO CPHF methods. The atomic charges were taken from the ESP fit using Breneman model (CHELPG). The Gaussian 98 package21 was employed for these calculations.
3. Results and Discussion
The calculated chemical shifts of the nitrogen atoms 15N for a - type and b - type tautomers occur in the different ranges: from about 5 - 309 to about - 23 for a - type tauto-mer and from about 5 - 225 to about - 80 for b-one (Table 1, Fig. 5)1. The shielding constants for the N3 and N10 atom in the 1,3,4 - thiadiazole and pyridine rings, respectively are almost equal whereas N4 atom is much less shielded1. The amino N6 atom is strongly shielded in 1 (about 5 - 308) but in 2 the shielding decreases by a few ppm ( to about 5 -304). The value of the chemical shift for the NH proton of 1 recorded in CDCl3 solution at 500,16 MHz, 5.81 ppm1 is in agreement with the resonanses of the amino protons. In 15N NMR spectrum of 1 the signal of the nitrogen
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Table 1. Calculated 15N and 'H NMR chemical shifts 8 [ppm] of type a and b tautomers
Comp.	15n	1H	
1a 2a	- 309 - -23		
1a	N6 - 131.57	H 14	8.125
	N3 - 77.78		
2a	N10 - 86.0	H 6	7.5
	N6 - 133.98		
1b 2b	- 225 - -80		

Fig. 5. The linear regression of shielding constants o [ppm] versus chemical shifts 8 [ppm] for 1a and 2a.
atom N6 at 5 - 308.581 supports the amino - type nitrogen. The calculated chemical shift of the nitrogen atom N6 5 - 131.57 confirms pyridine - type nitrogen atom (Table 1).
In the 15N-NMR spectrum of 1 the chemical shift of N10 at 5 - 80.011 supports pyrrole - type nitrogen atom of the pyridyl substituent. The calculated chemical shift value of N3 at 5 - 77.78 and 13C resonances line of C2 at 5 171.42 in 13C NMR spectrum 1 confirm pyridine - type nitrogen atom of 1. The 1H -13C HMQC correlation spectra show a correlation signal between H14 at 5 8.360 and C15 at 5 149.72. The above data prove the existence of the diradical resonance structures a0 A0 A (I)0 A (II)0 a'0 A'0 A (I)'o A (II)'0, (Figs 3, 6).
The calculated signal at 5 8,125 (H14) of 1 (Table 1) as well as the coupling constants J(H12H14) 1,0 Hz J(H11H14) 0,5 Hz1 confirm the lack of the charges on the pyridine ring. In the 2D 1H 13C HMBC spectra of 1 the cross - peaks between H14 and C14 at 5 8.150, 5 119.9 support the structures a A A (I) A (II) (Figs 3, 6).
The calculated chemical shift of N10 at 5 - 86.0 of 2 (Table 1)1 points to an amine - type nitrogen atom. The 1H
a,. A,, A(l),( A([[)a
—





a A A(l) A(f[) a' A' A(])' A([[)' a'u 4(1)'„ A(II)T0
Fig. 6. The resonance structures of the pyridyl substituent
13C HMQC correlation spectra of 2 show a correlation signal between H-14 at 5 8.290 and C15 at 5 149.7. The above data prove the diradical resonance structures a0c A0c A(I)0c A(II)oc, aoe Aoe A(I)oe A(II)oe (Fig. 3) and the lack of the charges over pyridine and 1,3,4-thiadiazole rings.3
The pyridyl H14 proton of the diradical resonance structures ao Ao A(I)o A(II)o a'o A'o A(I)'o A(II)'o, and aof Aof A(I)of A(II)of, a
oe Aoe A(I)oe A(II)oe is more intensly
deshielded by about 0.2 ppm and 0.15 ppm in relation to the structures a A A(I) A(II), respectively. The spectroscopic data support the conjugation of the aromatic n electrons of the pyridyl substituent with the n electrons of the C = N double bond of the 1,3,4 thiadiazole ring in the solution.
The signals of the NH proton and the pyridyl substituent in the 1H NMR spectra (100 MHz) of 1 support the ionic a A A(I), a1-5, A15 A(I)15 and radical resonance structures a'1-8, A'1-8 A(I)'1-8, a' A' A(I)' a'o A'o A(I)'o (Figs 1-4, 6, Tables 2-11). The resonance structures of the pyridine ring are shown on Fig. 4.
In the 13C-NMR spectrum of 1 the chemical shifts of C11 at 5 149.31 and C15 at 5 149.871 confirm pyridine -type nitrogen atom N10 of the structures a1 A1 A(I)1 a'1 A'1 A(I)'1 a'2 A'2 A(I)'2 and a5 A5 A(I)5, respectively. The1 chemical shift of C12 at 5 124.01 1 supports the pyridine -type nitrogen atom N10 of the structures a2 A2 A(I)2 a'3 A'3 A(I)'3 a'5 A'5 A(I)'5. The signal of C14 at 5 119.871 points to the structures a3 A3 A(I)3 a'4 A'4 A(I)'4 a5 A5 A(I)5. The signal of C13 at 5 136.771 confirms the structures a2 A2 A(I)2 a'3 A'3 A(I)'3 a4 A4 A(I)4 a'5 A'5 A(I)'5.
The 1H-NMR spectrum 17 (500 MHz) shows the signal of H14 of the structures a\ A\ A (I)\ a'5 A'5 A(I)'5 a'6 A'6 A(I)'6 at 5 8.185. In the 1H-11C HMB C and H MQC correlatinon spectra the signal of H14 at 5 8.180 exhibits a correlation to C14 at 5 119.7 and C12 at 5 124.0, C15 at 5 149.7, C5 at 5 160.0, respectively and confirms a'5 A'5 A(I)'5 a'6 A'6 A(I)'6 structures. In the 2D 1H-13C HMQC spectra the cross - peak between H11 at 5 8.340 and C14
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Table 2. The 'H NMR chemical shifts 8 [ppm] from TMS of 1.
Spectrum					
No / Solvent	H 7	H 8	H 9	Pyridin-2-yl	
				8.637	- 8.562 1H H 11
1i	3.922 - 4.061	5.772 - 6.148	5.104 - 5.399	8.135	- 7.988 1H H 13 H 14
DMSO	2H m	1H m	2H m	7.935	- 7.837 1H H 12 H 13
				7.503	- 7.336 1H H 14 H 12
				8.665	- 8.589 1H H 11
'2	3.988 - 4.086	5.809 - 6.187	5.133 - 5.435	8.174	- 8.010 1H H 13 H 14
DMSO	2H m	1H m	2H m	7.954	- 7.859 1H H 12 H 13
				7.517	- 7.381 1H H 14 H 12
				8.606	- 8.530 1H H 11
I3	4.003 - 4.086	5.782 - 6.160	5.191 - 5.482	8.245	- 8.145 1H H 13 H 14
CDCl3	2H m	1H m	2H m	7.859	- 7.688 1H H 12 H 13
				7.349	- 7.212 1H H 14 H 12
				8.601	- 8.525 1H H 11
I4	4.003 - 4.086	5.782 - 6.160	5.191 - 5.482	8.237	- 8.137 1H H 13 H 14
CDCl3	2H m	1H m	2H m	7.854	- 7.681 1H H 12 H 13
				7.342	- 7.205 1H H 14 H 12
				8.662	- 8.586 1.07H H 11
18 DMSO	4.069 - 3.988	5.804 - 6.180	5.143 - 5.431	8.174	- 8.023 1H H 13 H 14
-D2O	2.5H m	1.14H m	2.21H m	7.967	- 7.869 1.42H H 12 H 13
				7.532	- 7.395 1.21H H 14 H 12
Table 3. The 'H NMR chemical shifts 8 [ppm] from TMS of 1					
Spectrum					
No	H 7	H 8	H 9	Pyridin	1 - 2- yl
Solvent					
1	4.079 - 3.999	6.101 - 5.778	5.458 - 5.196	8.594 -	8.519 1H H 11
CDCl3	2H	1H	2H	8.232 -	8.143 1H H 13 H 14
				7.847 -	7.674 1H H 12 H 13
				7.336 -	7.200 1H H 14 H 12
2	4.083 - 4.003	6.106 - 5.782	5.463 - 5.196	8.580 -	8.537 1H H 11
CDCl3	2H	1H	2H	8.237 -	8.148 1H H 13 H 14
				7.847 -	7.674 1H H 12 H 13
				7.336 -	7.200 1H H 14 H 12
3	4.088 - 4.003	6.111 - 5.787	5.477 - 5.182	8.598 -	8.537 1H H 11
CDCl3	2H	1H	2H	8.237 -	8.148 1H H 13 H 14
				7.847 -	7.674 1H H 12 H 13
				7.331 -	7.195 1H H 14 H 12
4	4.088 - 4.003	6.111 - 5.787	5.482 - 5.186	8.603 -	8.528 1H H 11
CDCl3	2H	1H	2H	8.242 -	8.152 1H H 13 H 14
				7.852 -	7.683 1H H 12 H 13
				7.341 -	7.204 1H H 14 H 12
5	4.088 - 4.008	6.101 - 5.778	5.468 - 5.177	8.589 -	8.514 1H H 11
CDCl3	2H	1H	2H	8.387 -	8.345 1H H 11
				8.223 -	8.143 1H H 13 H 14
				8.077 -	7.974 1H H 13 H 14
				7.838 -	7.646 2H H 12 H 13
				7.397 -	7.143 2H H 14 H 12
6	4.083 - 4.003	6.106 - 5.782	5.482 - 5.196	8.598 -	8.523 1H H 11
CDCl3	2H	1H	2H	8.228 -	8.138 1H H 13 H 14
				7.852 -	7.678 1H H 12 H 13
				7.336 -	7.200 1H H 14 H 12
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at 5 119.9 as well as the correlation signals of H11 at 5 8.360 to C14 at 5 119.9 , C15 at 5 149,7 support structures a'2 A'2 A(I)'2 aj Aj A(I)1. The chemical shift of N10 in 15N-NMR spectrum of 1 at 5 - 74.78 supports the structures a2 A2 A(I)2, a'3 A'3 A(I)'3, a4 A4 A(I)4, a'5_8 A'5_8 A(I)'5_8.
The 1H-1H coupling constants J(H14H13) 8.0 Hz J(H13H14) 8.0 Hz J(H12H13) 8.0 Hz 1 of 1a tautomer confirm the positive charge at C13 atom of the structures a3 A3 A(I)3 a'4 A'4 A(I)'4 while the coupling constants J(H 12H13) 5.84 Hz J(H11H12) 5.6 Hz J(H13H11) 1.6 Hz 1 indicate the positive charge at C15 and the negative one at N10 atoms of pyridine substituent of the structures a4 A4
A(I)4 a'7 A'7A(I)V
In the range of the chemical shifts of NH proton from 5 7.125 to - 0.033 the transitions of electrons of 2p orbitals of C2 N3 N4 C5 and of 3p of S1 occur. In the 1H NMR spectra of 1 the chemical shifts of NH proton in the range from 5 7.125 to 6.500 ppm point to the transitions of electrons of p orbitals of the following polar structures:
-	1A'(1) 1A'o (1) 1Ao (1), 1A (2) 1A'(2) 1A'o (2) 1Ao (2), 1A (3), 1A (4) (Fig. 7),
-	1A (5) o 1A (I) (5), 1A'(5) o 1A (I)'(5), 1A'0 (5) o 1A (I)'o (5), 1A 0 (5) 01A (I) 0 (5), 1A (6) 01A (I) (6),
Table 4. The 'H NMR chemical shifts 5 [ppm] from TMS of 1.
1A'(6) O1A (I)'(6), 1A'0 (6) O1A(I)'0 (6), 1A 0 (6) O 1A (I)o (6), (Fig. 8)
-	1B (2) 1B'(2) 1B'o (2) 1Bo (2), 1B'(1) 1B'o (1) 1Bo (1), 1B (3), 1B (4) (Fig. 9), 1B (5) 1B'(5) 1B'o (5) 1Bo (5), 1B (5) 1B (2) 1B'(1) (Fig. 10), 1C (6) 1C (5) 1C (4) (Fig. 10),
-	1C (2) 1C'(2) 1C'o (2) 1Co (2), 1C (4), 1C (3), 1C'(5) 1C'o (5) 1Co (5), 1C (5) (Fig. 11).
In the 1H NMR spectra (100 MHz) of 1a tautomer in the range from 5 7.125 to 6.500 the nitrogen atoms N3, N4, N10 appear as pyridine - type, pyrrole - type nitrogen while N6 as pyridine - type A, pyrrole - type A(I) or in sp hybridization A(II).
In the 1H NMR spectrum 11 of 1 (100MHz, DMSO) the signal of H7 arises as three doublets of doublets at 5 3.922-3.954, 5 3.978-4.008, 5 4.032-4.061 (Figs 12, 13).
At the chemical shift 5 3.922-3.954 (dd) the electrons of 2p orbitals of N6 C7 show differences in their spin states. The differences in the coupling constants J(H8H9B) 17.6 Hz J(H8H7C) 18.8Hz, J(H8H9A) 10.6Hz J(H8H7D) 11.2Hz (100MHz)18 and the 13C NMR signals of allyl substituent C9 at 5 117.99, C8 at 5 132.80, C7 at 5 49.281 support the negatively charged pyridine - type nitrogen atom and positively charged allyl cation. The nitro-
Spectrum No				
Solvent	Pyridin	- 2- yl		
	H 14 - of the structures	H 14	, H 13	H 13 - of the structures
13(CDCl3)	a\A\o a'2A'2 ea'0Â'0	8.245	- 8.145	a\A\ o a'2A'2
14(CDCl3)	a'3A'3 0 a'1A'1	8.237	- 8.137	a2A2 ° a'3A'3
4(CDCl3)	a'2A'2 o a'1A'1 o a'0A'0	8.242	- 8.152	a1A1 o a'1A'1 o a A
2, 3(CDCl3)	a'3A'3 0 a'1A'1 0 a'0A'0	8.237	- 8.148	a2A2 o a'A'
1(CDCl3)	a'4A'4 o a'1A'1 o a'0A'0	8.232	- 8.143	a'3A'3 o a'A'
5(CDCl33)	a4A4 o a'1A'1 o a'0A'0	8.223	- 8.143	a4A4 o a'3A'3 o a'A'
6(CDCl33)	a2A2 o a4A4 o a'1A'1	8.228	- 8.138	a2A2 o a4A4 o a'3 A'3
18(DMSO-D2O)	a'4^'4 ° a'sA'5	8.174	- 8.023	a4A4 o a'3A'3
12(DMSO)	a'4A'4 ° a'6A'6	8.174	- 8.010	a4A4 o a'sA's
1j(DMSO)	a'sA's° a'6A'6 ° a'7A'7	8.135	- 7.998	a'sA'5 o a'3A'3
5(CDCl3)	a'8A'8 ° a'6A'6 ° a'7A'7	8.077	- 7.974	a'3A'3 ° a'sA'5 ° a'4A'4
Table 5. The !H-NMR chemical shifts 5 [ppm] from TMS of 1.				
Spectrum No				
Solvent	Pyridin -	2- yl		
	H 13 - of the structures	H 13,	H 12	H 12 - of the structures
18(DMSO-D2O)	a3A3 o a'3A'3 o aA	7.967 -	- 7.869	a5A5 o a1A1 o a'8A'8 o aA
12(DMSO)	a'3A'3 o a'5A'5 o aA	7.954	- 7.859	a g^A g o ^ a 7A 7
1j(DMSO)	a'4A'4 o a'5A'5 o aA	7.935	- 7.837	a'?A'7 ° a'6A'6
131(CDCl3)	a'sA'5 o a'3A'5 o a'0A'0	7.859	- 7.688	a'7A'7 o a'1A'1 o aA
134(CDCl33)	a'3A'3 o a'sA'5	7.854	- 7.681	a1A1 o a'2A'2 o a'A'
4(CDCl3)	a'3A'3 o a'4A'4 o a'0A'0	7.852	- 7.683	a2A2 o a'2A'2 o aA
6(CDCl33)	a'3A'3 ° a'4A'4	7.852	- 7.678	a2A2 o a'1A'1
1 - 3(CDCl3)	a'3A'3 ° a'sA'5 ° a'4A'4	7.847	- 7.674	a'1A'1 ° a'2A'2
5(CDCl3) 3	a'sA's o a'4A'4	7.838	- 7.646	a'6A'6 o a'1A'1 o a'3A'3
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Table 6. The 'H-NMR chemical shifts 8 [ppm] from TMS of 1.
Spectrum No / Solvent		Pyridin	- 2- yl	
	H 12 - of the structures	H 12,	H 14	H 14 - of the structures
18(DMSO-D2O)	a5A5 ^ a4A4 ^ a'6 A'6 ^ a'oA'o	7.532 -	7.395	a1A1 ^ a'1A'1 ^ aA
12(DMSO)	a'7A'7 ^ a'1A'1 ^ a'6A'6 ^ a'0A'0	7.517 -	7.381	a2A2 ^ a'jA'j ^ aA
1j(DMSO)	a'7A'7 ^ a'4A'4 ^ a'0A'0	7.503 -	7.336	a2A2 ^ a'4A'4 ^ aA
13(CDCl3)	a'4A'4 ^ a'2A'2 ^ a1A1	7.349 -	7.212	a'4A'4 ^ a'A'
14(CDC13)	a'4A'4 ^ a'1A'1 ^ a'0A'0	7.342 -	7.205	a'4A'4 ^ a'A'
5(CDC13)	a'7A'7 ^ a'4A'4 ^ a'2A'2	7.397 -	7.143	a'1A'1 ^ a'4A'4 ^ a'4A'4
	a'iA'1 a'5A'5 ^ a'2A'3			a'sA'5 ^ a'jA'j ^ a'7A^
4(CDC13)	a'4A'4 ^ a'jA'j ^ a'1A'1	7.341 -	7.204	a'4A'4 ^ aA
1, 2, 6(CDC13)	a'2A'4 ^ a'jA'j ^ a'0A'0	7.336 -	7.200	a'"A'4 ^ a'A' ^ a'5A'5
3(CDC13)	a'1A'1 ~ a'sA's	7.331 -	7.195	a'5A'5 ^ a'A' ^ a'6A'6
Table 7. The 1H-NMR chemical shifts 8 [ppm] from TMS of 1.
Spectrum No Solvent		Pyridin - 2- yl
	H 11	structures
12(DMSO)	8.665 -	8.589	a4A4 ^ a'4A'4 ^ a'7A'7 ^ aA		
1s(DMSO-D2O)	8.662 -	8.586	a4A4 ^ a'6A'6 ^ aA		
181(DMSO) 2	8.637 -	8.562	a3A3 ^ a5A5 ^ a'6A'6		
131(CDC13)	8.606 -	8.530	a'7A'7 ^ a'1A'1	^ a'sA'8	^ aA
43(CDC133)	8.603 -	8.528	a'7A'4 ^ a'sA'5	^ aA	
14(CDC313)	8.601 -	8.525	a'6A'6 ^ a'3A'3	^ aA	
3(CDC13)	8.598 -	8.537	a'sA'5 ^ a'sA'8	^ aA	
6(CDC133)	8.598 -	8.523	a'5A'5 ^ a'A'		
1(CDC13)	8.594 -	8.519	a'sA'5 ^ a'3A'3	^ a'oA'o	
5(CDC133)	8.589 -	8.514	a'jA'j ^ a'A'		
2(CDC133)	8.580 -	8.537	a'3A'3 ^ a'sA'5	^ a'sA'8	^ aA
5(CDC133)	8.387 -	8.345	a'1A'1 ^ a'2A'2	^ a1A1	
Table 8. The 'H NMR chemical shifts 8 [ppm] from TMS of the NH proton of 1A 1A(I), 1A' 1A(I)', 1B 1B', 1C 1C' tautomers
Spectrum No, (CDCl3)	5	NH	Structure
65	7.125	2.09H	1A (2, 3) ^ 1B (2-4) 1A (4) ^ 1C (3, 4)
65	7.040	0.786H	1A (2, 3, 4)s, 1B (2, 3, 4)s, 1C (2, 3, 4)s
66	7.120	3.03H	1A (5) ^ 1A (I) (5) ^ 1B (5) 1A (6) ^ 1A(I)(6) ^ 1C (6)
66	7.035	0.802H	1A (5)5 ^ 1A (I) (5)5, 1A (6)5 ^ 1A(I)(6)5, 1B (5)5, 1C (6)5 1C (5)5
14	6.771	1H s	1A' (1, 2), 1A'(5) ^ 1A (I)'(5), 1A'(6) ^ 1A(I)'(6), 1B'(1, 2, 5), 1C'(2, 5)
1 *	6.750 (H 3) 7.8 (H 12)		1B'(1, 2, 5)2
3	6.683	1H s	1A' (1, 2)2, 3,1A' (5)2, 3, ^ 1A (I)' (5)2, 3,1A'(6)2>3 ^ 1A(I)'(6)2, 3,
5	6.683	1.142H s	1B' (1, 2, 5)2, 3, 1C' (2, 5)2, 3
2	6.674	1H s	1A' (1, 2)4 5 1A' (5)4 5 ^ 1A (I)' (5)4 5 1A'(6)4 5 ^ 1A(I)'(6)4 s 1B'(1, 2, 5)4, 1C'(2,' 5)4, 5 " ' "
1	6.657	1H s	1A' (1, 2)6, 1A' (5)6 ^ 1A (I)' (5)6, 1A'(6)6 ^ 1A(I)'(6)6, 1B'(1, 2, 5)6, 1C'(2, 5)6
6	6.632	1H s	1A' (1, 2)7, 1A' (5)7 ^ 1A (I)' (5)7, 1A'(6)7 ^ 1A(I)'(6)7, 1B'(1, 2, 5)7, 1C'(2, 5)7
4	6.500	1.009H s	1A' (2)8,1A' (5)8 ^ 1A (I)' (5)8,1A'(6)8 ^ 1A(I)'(6)8, 1B'(1, 28, 5)8, 1C'(2)8
* 2D !H !H COSY spectrum of 1
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gen atom N6, the pyridine - type, is occupied with eight electrons. The coupling constants J(H8H9B) 17.6 Hz, J(H8H9A) 10.6Hz J(H8H9B) 17.3 Hz J(H8H9A) 10.9 Hz (100 MHz)18 J(H9BH9A) 1.2 Hz (500 MHz)1 point to the differences in the spin states of electrons of 2p orbitals of pyri-dine - type nitrogen and carbon atoms N6 C7 of 1. At the
Table 9. The 'H-NMR chemical shifts 5 [ppm] from TMS and the 'H-'H long - range coupling constants [Hz] of 1
Spectrum No. (CDCl3)	5	J	NH
4	8.528	J(H„H9A) 37.280	
6	8.598	J(HJJH9A) 38.144	0.1 H
1	7.754	J(H12H9A) 38.336	0.43 H
4	8.584	J(HnH,A) 38.400	
6	7.852	J(H12H9A) 38.912	0.14 H
5	7.998	J(HbH9A) 40.064	0.756 H
5	7.974	J(H13H9A) 39.296	
4	7.331	J(H14H9A) 39.392	0.46 H
4	7.341	J(H14H9A) 40.640	
2	6.008	J(H8H12) 39.872	0.071 H
2	5.890	J(H8H13) 41.728	
6	5.839	J(H8H12) 39.936	0.03 H
1	8.152	J(H13H9A) 40.672	0.38 H
5	7.819	J(H12H9A) 40.839	1.356 H
3	6.012	J(H8H13) 40.839	0.019 H
3	5.895	J(H8H13) 42.368	
3	5.886	J(H8H14) 39.168	
1	8.223	J(H13H9A) 41.760	0.38 H
6	7.697	J(H,9H9A) 41.984	0.14 H
6	8.218	J(H13H9B) 49.940	0.172 H
4	8.594	J(H„H9B) 49.439	
5	8.223	J(HbH9B) 43.776	0.633 H
Table 10. The !H-NMR chemical shifts 5 [ppm] from TMS and the 1H-1H long - range coupling constants [Hz] of 1			
Spectrum No. (CDC13)	5	J	NH
1	3.999	J(H7DHn) 37.696	0.822 H
99	3.999	J(H6H19) 40.960	0.199 H
3	(-0.033)	J(H6Hn) 38.979	0.099 H
66	4.018	J(H6Hn) 38.656	0.19 H
5	5.266	J(H9A!^12) 40.960	0.9 H
5	5.449	J(H9AH13) 39.980	
3	5.477	J(H9AHb) 40.199	0.26 H
3	5.787	J(H8H19) 43.139	
4	5.214	J(H9BHm) 43.719	0.24 H
4	5.280	J(H9AH12) 40.994	
chemical shifts 5 3.978-4.008 (dd), the electrons of 2p orbitals of N6 C7 show no differences in their spin states. The coupling constants J(H8H9B) 17.1 Hz J(H9BH8) 17.1 Hz, J(H8H9A) 10.1 Hz J(H9AH8) 10.1 Hz, J(H9BH9A) 1.0 Hz (500 MHz)1 point to the lack of the differences in the spin states of electrons of 2p orbitals of pyridine - type nitrogen atom N6 C7 of 1, structure A, the exocyclic nitrogen atom N6 is surrounded by seven electrons.. The magnitude of the couplings J(H7H8) = J(H8H7) 5.6 Hz (500 MHz)1 for 1 confirms pyrrole - type nitrogen atom N6, structures 1A (I) 1A (I) 01A (I)'01A (I)' and the possible transformation of sp2 ^ sp hybridization, the structures 1A (I) O 1A (II), 1A (I)0 O 1A (II)0, 1A (I)'0 O 1A (II)'0, 1A (I)' O 1A (II)'. The calculated chemical shift value of H6 at 5 7.5 of 2 (Table 1) points to the lack of the differences in the spin states of electrons of 2p orbitals of C2 N3, C2 N6, N6 C7.
The doublet of a doublet at 5 4.032-4.061 supports the 1A (I) (5, 6), 1A (I)'(5, 6), 1A (I)'o (5, 6), 1A (I)o (5, 6) structures (Figs 12, 13, 8).
In 15N NMR spectrum of 1 the chemical shift of N4 5-22.981 points to the pyrrole - type nitrogen atom and to the presence of the polar structures 1A'(1) 1A 0 (1) 1A'0 (1) (Fig. 7).
The 1H 1H long-range coupling constants in the 37.280 Hz - 43.776 Hz range18 support the coupling of the protons of the pyridyl and - N - CH2-CH = CH2 groups via 2p orbitals of C14 C7 of the rigid structures A' A'a and sp2 hybridization of the exocyclic nitrogen atom N6 (spectra 1-6, Table 9, Fig. 14). The signals at 5 - 0.033-5.787 (Table 10, spectra 1, 3-66) confirm the transformation of sp2 ^ sp3 of N6 and A' O a', A'a O a'a resonance structures.
In the 1H NMR spectra 13, 4 (100 MHz, CDCl3) the coupling constants of the protons J(H8H9B) 17.3 Hz, J(H8H7C) 18.9 Hz, J(H8H7D) 11.5 Hz, J(H8H9A) 10.9 Hz 18 confirm the sp2 hybridization of nitrogen and carbon N6 C7 atoms. The coupling constants of the protons J(H8H9B) 12.3 Hz, J(H8H9A) 8.5Hz, J(H8H7C) 7.5Hz, J(H8H7D) 77.4 Hz support the sp3 hybridization of carbon C7 atom. The coupling constants of the protons J(H8H7C) 8.2 Hz, J(H8H7D) 7.8 Hz18 confirm the changes of sp2 ^ sp3 hybridization of the nitrogen and carbon atoms N6 C7.
The 1H 1H long-range coupling constants J(HgHn) 38.272 Hz, J(H6Hn) 38.656 Hz (Table 10) support the structures A'(1) A'(5) A'(6) (Figs 7, 8).
In the 1H NMR spectra 65, 66 (100MHz) of 1 the signals at 5 7.125 and 5 7.120 support the co - existence of two tautomeric forms A (2, 3) ^ B (2-4), A (4) ^ C (3, 4) and A (5) O A (I) (5) ^ B (5) or A (6) O A (I) (6) ^ C (6), respectively. The intensities of the signals at 5 7.125 (2,09H, Fig. 15) and 5 7.120 (3.03H, Fig. 15) indicate the interconvertion of 1A (2) ^ 1B (2, 4), 1A (3) ^ 1B (3, 4), 1A (4) ^ 1C (3, 4) and 1A (5) O 1A (I) (5) ^>1B (5) or 1A (6) 01A (I) (6) ^ 1C (6) tautomers, respectively (Figs 9-11, Table 8).
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IA'<2>
—CH?—CH
1A(2)
-Oii—CH = CH,	0
£	v	" N—N
y IJ I
"J—N / V/^NH-CH, —-CH =CH,
IA„(2)
© e
N—N
NH-CH,-CH —CH,
IA(3)
-INI
NH—ci u —
CH =CH->
1A(4)
Fig. 7. The resonance structures of allyl- 5-(pyridin-2-yl)-[1,3,4] thiadiazol-2-yl)-amine 1A 1A'
Fig. 8. The resonance structures of allyl-(5-(pyridin-2-yl)-[1,3,4] thiadiazol-2-yl)-amine 1A 1A' 1A (I) 1A(I)'
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Fig. 9. The tautomeric interconvertions of 1A ^ 1B tautomers.
Fig. 10. The tautomeric transitions of 1A ^ 1A(I) ^ 1B and 1A ^ 1A(I) ^ 1C tautomers
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"N — CHj—CH 1C (2)
Fig. 11. The tautomeric balance of 1A ^ 1C tautomers
Fig. 12. The !H NMR signals of H 7 proton at 3.922 ppm - 4.061 ppm (spectrum 1p DMSO, 100 MHz)
Fig. 13. The 1H NMR signals of H 7 proton at 3.922 ppm - 4.061 ppm (spectrum 11, DMSO, 100 MHz)
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Fig. 14. The resonance rigid structures A', A'a of allyl-(5-pyridin-2-yl-[1,3,4] thiadiazol-2-yl)-amine
The signals at 5 7.040 (0.786H) and 5 7.035 (0.802H) correspond to the NH proton of the structures 1A (2, 3, 4) 51B (2, 3, 4) 51C (2, 3, 4) 5, and 1A (5)s O1A (I) (5)5, 1A (6)5 0 1A (I) (6)5, 1B (5)5 1C (6)5 1C (5)5, respectively (Figs 9-11, 4, spectra 65, 66, Table 8).
In the 2D 1H 1H COSY correlation spectrum the cross - peak between H3 at 5 6.750 and H12 at 5 7.8 supports B'(1, 2, 5)2 structures of b - type tautomer of 1 ( Fig.
Fig. 15. The 1H NMR signals of NH proton at 7.125 ppm, 7.120 ppm (spectra 65, 66)
Fig. 16. The resonance structures of 3H allyl-(5-pyridin-2-yl-[1,3,4] thiadiazol-2-ylidene)-amine 1B'
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Fig. 17. The resonance structures 4H-(3-phenyl-allyl)-(5-pyridin-2-yl-[1,3,4] thiadiazol-2-ylidene) amine 2C, 2C'.
Table 11. The 'H-NMR chemical shifts 8 [ppm] from TMS of the NH group of tautomers 1A 1A'.
support the sp3 hybri-
Spectrum No, Solvent	5		NH	Structure
1j (DMSO)	8.637 -	8.562	0.08 H	1A 1A'
13 (CDCl3)	8.606 -	8.530	0.2 H	1A11A2
14 (CDCl3)	8.601 -	8.525	0.05 H	
3 (CDCl3)	8.598 -	8.537	0.23 H	
6 (CDCl3)	8.598 -	8.523	0.1 H	
1 (CDCl3)	8.594 -	8.519	0.38 H	
5 (CDCl3)	8.589 -	8.514	0.637 H	
2 (CDCl3)	8.580 -	8.537	0.08 H	
	8.077 -	7.974	0.756 H	1A'1
5(CDCl3) 4(CDCl3)	7.852 -	7.683	0.13 H	1A'2
	7.852 -	7.678	0.14 H	1A'3
6(CDCl3) 1(CDCl3)	7.847 -	7.674	0.43 H	
	7.847 -	7.674	0.18 H	
2(CDCl3)	7.847 -	7.674	0.25 H	
3(CDCl3)	7.838 -	7.646	1.356 H	
5(CDCl3) 17(CDCl3)	7.78 -	7.73	0.505 H	
J(H8H7C) 7.6 Hz, J(H8H7D) 7.6 Hz dization of C7 carbon atom.
In the 'H-NMR (100 MHz) spectra of 1 the NH proton signals in the 8 8.637-8.514 and 8 8.077-7.646 range confirm the 1A, 1A', 1Ar 1A2 and 1A'r 1A'2 1A'3 resonance structures, respectively (Table 11)2. The signals at 8 8.594 /(H11H9B) 42.432 Hz , 8 8.584 J(H
11H9A) 38.400
16, Table 8). In the 1H-NMR spectrum 85 of product 2 re-
corded in CDCl3 solution at 100 MHz the considerable deshielding of the NH proton at 8 13.64 22 indicates the possible intramolecular hydrogen bond and supports 2C' 2C (I)' 2C (II)' tautomers (Fig. 17).
In the 1H NMR spectrum 11 (100 MHz, DMSO) of 1 the magnitude of the couplings J(H8H7D) = J(H8H7C) 8.2 Hz18 support the changes of sp2 ^ sp3 hybridization of the nitrogen and carbon atoms N6 C7. The coupling constants of the protons J(H8H9B) 15.4 Hz, J(H8H9A) 8.5 Hz,
Hz, 8 8.528 J(HnH9A) 37.280 Hz and 8 7.998 J(H13H9A) 40.064 Hz (spectra 4, 5 Table 9)2 point to the transition of A' o A and o Ax tautomers as well as to the rapid exchange at the NH group hydrogen of structures A A'.
The interconvertions of the structures 1A o 1A' o 1A'a, 1A (I) o 1A (I)' o 1A (I)'a and the rapid exchange of the NH hydrogen suggest the proton transfer of 1A o 1A (I) ^ 1B, 1A o 1A (I) ^ 1C tautomers via solvent. Doubled signals of the protons corresponding to both tautomeric forms are present in the 1H-NMR (100 MHz) spectra of 1 (Fig. 15, Table 8). The proton transfer reactions for different systems have been described in the lite-rature23, 24.
In the 1H NMR (100 MHz) spectra 14, 1-6 the NH proton singlets in the 8 6.771 to 6.500 range with the intensity of 1H confirm the resonance structures 1A'(1, 2), 1A'(5) o 1A (I)'(5), 1A'(6) o 1A (I)'(6), 1B'(1, 2, 5), 1C'(2, 5) (Table 8, Figs 7-11, 4).
4. Conclusions
The 1H, 13C, 15N NMR studies (100MHz) of allyl-( 5-pyridin-2-yl-[1,3,4] thiadiazol-2-yl-) amine support the A o A' o A'a, A(I) o A(I)' o A(I)'a structures. The intensities of the signals of N-H proton at 5 7.125 and 5 7.120 confirm the balance of two tautomeric forms A o
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A (I) ^ B, A o A (I) ^ C in the solution. Doubled signals of the NH proton in the 'H-NMR (100 MHz) spectra of 1 (Fig. 15, Table 8) confirm both tautomeric forms. Because of the rapid exchange of NH group hydrogen in this case the pathway of the proton transfer via solvent may take place.
The signals of H7 in the 'H NMR spectrum 1' (100 MHz, DMSO) of 1 at 8 3.922-3.954, 8 3.978-4.008, 8 4.032-4.061, the coupling constants of the protons of al-lyl-substituent as well as the calculated chemical shift of the nitrogen atom N6 8 - 131.57 confirm 1A 1A' 1A'a 1A (I) 1A (I)' 1A (I)'a and 1B 1B', 1C 1C' tautomers.
5. References
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Povzetek
Radikalske in ionske strukture alil-(5-piridin-2-il-[1,3,4]tiadiazol-2-il)-amina 1A ^ 1A' ^ 1A'a, 1A (I) ^ 1A (I)' ^ 1A (I)'a so bile določene z uporabo 1H (100 MHz, 500 MHz) 13C and 15N NMR spektroskopije in B3LYP/6-31G** računi. Spekter 1H NMR (100 Mhz) nam je potrdil obstoj tavtomernega prehoda 1A ^ 1A (I ) ^ 1B, 1A ^ 1A (I ) ^ 1C.
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