Molecular Sciences the Electronic Structure of the Nitrogen Atoms of Allyl (5- Pyridin-2-yl-[1,3,4]-thiadiazol-2-yl)-amine

The resonance structures of


N
The calculated 15 N-, 1 H-chemical shifts and the 15 N-, 1 H-, 13 C-signals of the respective 15 N-, 1 Hand 13 C-NMR spectra suggest changes in the electron configuration of the exo -and endocyclic nitrogen atoms of the 1,3,4-thiadiazole and pyridine rings.The aim of the present paper was to describe the electronic structure of the nitrogen atoms of tautomer 1a in the range of the chemical shifts of the NH group proton from 8.665 ppm to 7.233 ppm.

Results and Discussion
The calculated chemical shifts of the 15 N nitrogen atoms for type a and b tautomers of allyl-(1) and 3-phenylallyl-(5-pyridin-2-yl- [1,3,4]-thiadiazol-2-yl)-amine (2) occur in different ranges: from about -309 ppm to about -23 ppm for the type a tautomer and from about -225 ppm to about -80 ppm for the b one (Table 1, Figure 4) [10].The amino N6 atom is strongly shielded in 1 (about -308 ppm) but in 2 the shielding decreases by a few ppm (to about -304 ppm).The shielding constants for the N3 and N10 atom in the 1,3,4-thiadiazole and pyridine rings, respectively, are almost equal, whereas the N4 atom is much less shielded [10].In the 1 H-NMR spectra the N6 nitrogen atom of 1a appears as an amine -type a, pyridine -type A, pyrrole -type A (I) (Figures 1-3, 5, 6).The 5.81 ppm value of the chemical shift for the proton of NH group of 1 recorded in CDCl 3 solution at 500.16MHz [10] is in agreement with the resonances of the amino protons.The signal of the N6 nitrogen atom in the 15 N-NMR spectrum appears at -308.58 ppm [10] and supports the amino -type nitrogen.The differences in the coupling constants J(H 8 H 9B ) 17.6 Hz, J(H 8 H 7C ) 18.8Hz, J(H 8 H 9A ) 10.6Hz J(H 8 H 7D ) 11.2Hz (100MHz) [8] and the 13 C-NMR signals of C9 allyl substituent at 117.99 ppm, C8 at 132.80 ppm and C7 at 49.28 ppm [10] support the negatively charged pyridine -type nitrogen atom and positively charged allyl cation.The coupling constants J(H 8 H 9B ) 17.6 Hz, J(H 8 H 9A ) 10.6 Hz, J(H 8 H 9B ) 17.3 Hz, J(H 8 H 9A ) 10.9 Hz (100 MHz) [8] and J(H 9B H 9A ) 1.2 Hz (500 MHz) confirm the reversed electron demand of the 2p orbitals of the pyridine -type nitrogen and carbon atoms N6 C7 of 1.The exocyclic nitrogen atom, the pyridine -type, is occupied with eight electrons.The coupling constants J(H 8 H 9B ) 17.1 Hz, J(H 9B H 8 ) 17.1 Hz, J(H 8 H 9A ) 10.1 Hz, J(H 9A H 8 ) 10.1 Hz, J(H 9B H 9A ) 1.0 Hz (500 MHz) [10] point to the lack of the differences in the spin states of electrons of 2p orbitals of pyridine -type nitrogen N6 and C7 atoms of 1, the exocyclic nitrogen atom N6 is surrounded by seven electrons.The calculated chemical shift of N6 at -131.57ppm (Table 1) [10] supports pyridine -type nitrogen.The magnitude of the couplings J(H 7 H 8 ) = J(H 8 H 7 ) = 5.6 Hz (500 MHz) for 1 confirms a pyrrole -type nitrogen atom N6 A(I) and the possible transformation of sp 2 ⇔ sp.
The calculated signal of H14 at 8.125 ppm (Table 1) as well as the 1 H-1 H coupling constants J(H 12 H 14 ) 1.0 Hz, J(H 11 H 14 ) 0.5 Hz [10] of structure a confirm the absence of charges on the pyridine ring.
In the 15 N-NMR spectrum of 1a tautomer, the chemical shift of N10 at -80.01 ppm [10] supports the pyrrole -type nitrogen atom of the pyridyl substituent.The calculated chemical shift of N3 at -77.78 ppm (Table 1) [10] confirm a pyridine -type nitrogen atom of tautomer 1a and the lack of the differences in the spin states of electrons of 2p orbitals of N3 C2.The 1 H - 13 C HMQC correlation spectra show a correlation signal between H14 at 8.360 ppm and C15 at 149.7 ppm.The above data prove the existence of the diradical resonance structures a 0 A 0 A(I) 0 a' 0 A' 0 A(I)' 0 (Figures 3, 5 -7) and the lack of the charges over the pyridine and 1,3,4 thiadiazole rings.In the 2D 1 H- 13 C HMBC spectra the cross -peak between H14 and C14 at 8.150 ppm and 119.7 ppm supports structures a A A(I) (Figures 3, 5 -7).The pyridyl H14 proton of the diradical resonance structures a 0 A 0 A(I) 0 a' 0 A' 0 A(I)' 0 is more intensly deshielded by about 0.2 ppm in relation to the structure a A A(I).The spectroscopic data support the conjugation of the aromatic π electrons of the pyridyl substituent with the π electrons of the C = N double bond of the 1,3,4 thiadiazole ring in solution.

, respectively
The calculated chemical shift of N10 at -86.0 ppm of 2a tautomer (Table 1) [10] point to an amine -type nitrogen atom.The 1 H-data (100 MHz, 500 MHz), 13 C-and 15 N-NMR spectra and the theoretical calculations of the studied system point to the transformation of pyridine -type nitrogen atom to pyrrole -type as well as to amine -type nitrogen of 1,3,4 -thiadiazole and pyridine rings, the structures a A A(I) , a 0 A 0 A(I) 0 , a' 0 A' 0 A(I)' 0 and a' A' A(I) ' (Figures 1-3).
The calculated chemical shift of NH group at 7.5 ppm of tautomer 2a (Table 1) [10] supports sp 2 hybridization of N6 as well as the absence of the charges over 1,3,4 thiadiazole ring.The calculated chemical shift of N6 at -133.98 ppm of tautomer 2a (Table 1) [10] supports pyridine -type nitrogen atom.
The changes concern either the phases of p orbitals of N3 N4 and N10 nitrogen atoms of 1,3,4thiadiazole and pyridine rings, respectively see the structures A 0b A 0d (Figure 11) or the spin states of electrons of sp 2 orbitals, the structures A 0 , A 0a , (Figures 9, 10) and support the transformation of pyridine -type nitrogen atom to pyrrole -type nitrogen atom in the second case.The simultaneous changes of the spin states of electrons of sp 2 orbitals and of the phases of p orbitals of N3 N4 N10 nitrogen atoms of 1,3,4 -thiadiazole and pyridine rings as well as the absence of the reversed electron demand cause the transformation of pyridine nitrogen atom to amine nitrogen atom, the structures A 0c A 0e (Figure 12).Consequently the structures A 0 , A 0a , (Figures 9, 10) show the pyrroletype nitrogen atoms N3 N4 N10 and the lack of the differences in the phases of p orbitals of 1S 2C 3N 4N 5C 6N 10N 11C -15C.In the structures A 0b A 0d (Figure 11) the nitrogen atoms N3 N4 N10 are the pyridine -type but the phases of p orbitals of N3 N10 and N4 N10 differ from p orbitals of 1S 2C 4N 5C 6N 11C -15C and 1S 2C 3N 5C 6N 11C -15C atoms, respectively.In the structures A' A' a and A' 0 A' 0a (Figures 13, 3) the nitrogen atom N10 is pyridine -type and p orbitals of N10 C11 -C13 and N10 C11 C13 C14, respectively show no differences in their phases.
The differences in the resonances of NH proton in the range from 8.637 ppm to 7.233 ppm are caused by the atomic charge over the pyridine ring.To assign the resonance structures of 1 in the range from 8.637 ppm to 7.233 ppm the chemical shifts of NH group, the 15 N-, 13 C-and 1 H-signals in 15 N-, 13 C-and 1 H-NMR spectra (100 MHz, 500 MHz) of 1 as well as the 1 H-1 H coupling constants of the pyridyl substituent have been analyzed.The resonance structures of the pyridine ring are shown on Figure 8.
In the 13   The 1 H-NMR spectrum 1 7 (500 MHz) shows the signal of H14 of the structures a' 1 A' 1 A(I)' 1 a' 5 A' 5 A(I)' 5 a' 6 A' 6 A(I)' 6 at 8.185 ppm.In the 1 H- 13 C HMBC and HMQC correlatinon spectra the signal of H14 at 8.180 ppm exhibits a correlation to C14 at 119.7 ppm and C12 at 124.0 ppm, C15 at 149.7 ppm, C5 at 160.0 ppm, respectively and confirms a' 5 A' 5 A(I)' 5 a' 6 A' 6 A(I)' 6 structures.In the 2D 1 H- 13 C HMQC spectra the cross -peak between H11 at 8.340 ppm and C14 at 119.9 ppm as well as the In the 1 H-NMR (100 MHz) spectra 1 1 -  10) correspond to the NH group proton of tautomers 1A 5 and 1A 4 , respectively.The broaded triplets suggest that these protons take part in the intermolecular hydrogen bonds.The broaded triplet in the 1 H-NMR spectrum 1 1 indicates the slow exchange of the proton of NH group, due to this fact, the coupling of the protons H6 H7 may be observed and support 1A tautomer.These signals are the averaged ones in consequence of the rapid transitions of hydrogen atom between the exocyclic nitrogen atom N6 and N3 N4 ones of 1,3,4-thiadiazole ring, then degenerated broaded triplet at 8.310 ppm in the 1 H-NMR spectrum 1 2 point to the 1A 4 1B 4 1C 4 tautomers..They disappear in D 2 O (spectrum 1 8 ) .In 1 H-NMR spectrum 5 (100 MHz, CDCl 3 ) in the range from 7.397 ppm to 7.143 ppm a signal with an intensity of 7.5 H is seen (Figure 14, Tables 3, 11).

Conclusions
The investigation of this specific tautomeric equilibrium support higher stability A, B and high energy diradical A' A' a , B', C' structures in the solution.The presently studied interconversions of the tautomeric forms A' A' a B' C' confirm pyridine -type nitrogen atoms for N10 N4 N6 and aminetype for N4 N3 of the pyridine and 1,3,4 -thiadiazole rings.The intensities of the signals of the NH group in the 100 MHz 1 H-NMR spectra in the range from 8.637 ppm to 7.143 ppm (Tables 10, 11) confirm the mesomeric resonance structures A, B, A' B' C' in solution.
The molecular geometries and properties corresponding to the local minima of the energy were calculated at the DFT level of the theory with the B3LYP density functional and the 6-31G* basis set [24,25].The same basis set and functional were used for the 1 H-, 13 C-and 15 N-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 package [26] was employed for these calculations.
C-NMR spectrum of 1 the chemical shifts of C11 at 149.31 ppm and C15 at 149.87 ppm confirm pyridine -type nitrogen atom N10 of the structures a 1 A 1 A(I) 1 a' 1 A' 1 A(I)' 1 a' 2 A' 2 A(I)' 2 and a 5 A 5 A(I) 5 , respectively.The chemical shift of C12 at 124.01 ppm supports the pyridine -type nitrogen atom N10 of the structures a 2 A 2 A(I) 2 a' 3 A' 3 A(I)' 3 a' 5 A' 5 A(I)' 5 .The signal of C14 at 119.87 ppm points to the structures a 3 A 3 A(I) 3 a' 4 A' 4 A(I)' 4 a 5 A 5 A(I) 5 .The signal of C13 at 136.77 ppm confirms the structures a 2 A 2 A(I) 2 a' 3 A' 3 A(I)' 3 a 4 A 4 A(I) 4 a' 5 A' 5 A(I)' 5 .

1 H 2 A' 2 A(I)' 2 a 1 A 1 A(I) 1 .a 2 A 2 A 8 .
correlation signals of H11 at 8.360 ppm to C14 at 119.9 ppm, C15 at 149,7 ppm support structures a' The chemical shift of N10 in15 N-NMR spectrum of 1 at -74.78 ppm supports the structures The 1 H-1 H coupling constants J(H 14 H 13 ) 8.0 Hz J(H 13 H 14 ) 8.0 Hz J(H 12 H 13 ) 8.0 Hz of 1a tautomer confirm the positive charge at C13 atom of the structures a 3 A 3 A(I) 3 a' 4 A' 4 A(I)' 4 while the coupling constants J(H 12 H 13 ) 5.8 Hz J(H 11 H 12 ) 5.6 Hz J(H 13 H 11 ) 1.6 Hz indicate the positive charge at C15 and the negative one at N10 atoms of pyridine substituent of the structures a 4 A 4 A(I) 4 a' 7 A(I)' 7 .

Table 1 .
Calculated 15 N-and 1 H-NMR chemical shifts δ [ppm] of type a and b tautomers

Table 10 .
The 1 H-NMR chemical shifts δ [ppm] from TMS of the NH group of tautomer 1A

Table 11 .
The 1 H-NMR chemical shifts δ [ppm] from TMS of the NH group of tautomer 1A' (in CDCl 3 )