The formation of an intramolecular hydrogen bond in pyrrolo[1,2-a]pyrazin-1(
Pyrrolo[1,2-a]pyrazin-1(
An attempt has been made previously to identify spectroscopic properties of some pyrrolopyrazinones [
We consider here a series of pyrrolopyrazinones (Scheme
Schematic representation of the structure and atom numbering of pyrrolopyrazinone derivatives (2–22) where R2 = CH3, CH2Cl, or CHCl2; R3 = H, Cl, CH3, (CH2)nCH3, (CH2)nCH2Cl, (CH2)nNH2, NH2, and (CH2)3NHC(NH)NH2.
Schematic representation of the endophyte-infected plant.
Selected bond lengths of pyrrolo[1,2-a]pyrazin-1(
Compound | Bond length [Å] | Pyrrole ring | Calculated |
Calculated | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 | 1.376 | 1.383 | 1.428 | 1.382 | 1.376 | 0.833 | 0.071 | 0.096 | 1568 | ||||
1a | R2 = CH3, R3 = H | 1.383 | 1.390 | 1.418 | 1.390 | 1.383 | 0.876 | 0.082 | 0.043 | 1578 | |||
1b | R2 = CH2Cl, R3 = H | 1.384 | 1.392 | 1.416 | 1.391 | 1.384 | 0.882 | 0.082 | 0.036 | 1575 | |||
1c | R2 = CHCl2, R3 = H | 1.385 | 1.393 | 1.414 | 1.392 | 1.384 | 0.885 | 0.082 | 0.032 | 1573 | |||
2 | R2 = CH3, R3 = H | 1.396 | 1.390 | 1.416 | 1.390 | 1.396 | 0.848 | 0.097 | 0.055 | 1564 | |||
3 | R2 = CH2Cl, R3 = H | 1.396 | 1.391 | 1.415 | 1.390 | 1.396 | 0.852 | 0.095 | 0.053 | 1567 | |||
4 | R2 = CHCl2, R3 = H | 1.389 | 1.393 | 1.413 | 1.393 | 1.388 | 0.875 | 0.091 | 0.034 | 1565 | |||
5 | R2 = CH3, R3 = Cl | 1.394 | 1.391 | 1.415 | 1.391 | 1.393 | 0.859 | 0.095 | 0.046 | 1562 | |||
6 | R2 = CH2Cl, R3 = Cl | 1.393 | 1.392 | 1.414 | 1.391 | 1.393 | 0.862 | 0.093 | 0.045 | 1565 | |||
7 | R2 = CHCl2, R3 = Cl | 1.391 | 1.392 | 1.413 | 1.392 | 1.391 | 0.869 | 0.091 | 0.039 | 1564 | |||
8 | R2 = CH3, R3 = NH2 | 1.391 | 1.395 | 1.412 | 1.395 | 1.390 | 0.873 | 0.098 | 0.029 | 1555 | |||
9 | R2 = CH2Cl, R3 = NH2 | 1.390 | 1.394 | 1.412 | 1.394 | 1.390 | 0.875 | 0.095 | 0.030 | 1560 | |||
10 | R2 = CHCl2, R3 = NH2 | 1.389 | 1.397 | 1.409 | 1.397 | 1.388 | 0.883 | 0.096 | 0.021 | 1555 | |||
11 | R2 = CH3, R3 = CH3 | 1.392 | 1.392 | 1.415 | 1.391 | 1.391 | 0.863 | 0.095 | 0.042 | 1564 | |||
12 | R2 = CH2Cl, R3 = CH3 | 1.391 | 1.392 | 1.392 | 1.392 | 1.391 | 0.905 | 0.053 | 0.042 | 1567 | |||
13 | R2 = CHCl2, R3 = CH3 | 1.389 | 1.393 | 1.413 | 1.393 | 1.388 | 0.875 | 0.091 | 0.034 | 1565 | |||
14 | R2 = CH3, R3 = CH2CH2CH2Cl | 1.390 | 1.392 | 1.415 | 1.391 | 1.390 | 0.865 | 0.093 | 0.042 | 1565 | |||
15 | R2 = CH2Cl, R3 = CH2CH2CH2Cl | 1.390 | 1.392 | 1.414 | 1.391 | 1.389 | 0.868 | 0.091 | 0.041 | 1568 | |||
16 | R2 = CHCl2, R3 = CH2CH2CH2Cl | 1.387 | 1.393 | 1.413 | 1.392 | 1.387 | 0.876 | 0.089 | 0.035 | 1567 | |||
17 | R2 = CH3, R3 = CH2CH2CH2NH2 | 1.390 | 1.392 | 1.415 | 1.392 | 1.390 | 0.864 | 0.095 | 0.040 | 1561 | |||
18 | R2 = CH2Cl, R3 = CH2CH2CH2NH2 | 1.390 | 1.392 | 1.414 | 1.392 | 1.389 | 0.869 | 0.092 | 0.039 | 1567 | |||
19 | R2 = CHCl2, R3 = CH2CH2CH2NH2 | 1.388 | 1.393 | 1.413 | 1.393 | 1.387 | 0.877 | 0.090 | 0.033 | 1565 | |||
20 | R2 = CH3, R3 = CH2CH2CH2NHC(NH)NH2 | 1.390 | 1.392 | 1.415 | 1.391 | 1.390 | 0.865 | 0.094 | 0.042 | 1564 | |||
21 | R2 = CH2Cl, R3 = CH2CH2CH2NHC(NH)NH2 | 1.390 | 1.392 | 1.414 | 1.392 | 1.390 | 0.869 | 0.092 | 0.040 | 1568 | |||
22 | R2 = CHCl2, R3 = CH2CH2CH2NHC(NH)NH2 | 1.387 | 1.393 | 1.413 | 1.393 | 1.387 | 0.877 | 0.089 | 0.034 | 1566 | |||
1a | R2 = CH3, R3 = H | 1.390 | 1.462 | 1.525 | 1.453 | 1.383 | 1.470 | 1705 | |||||
1b | R2 = CH2Cl, R3 = H | 1.404 | 1.467 | 1.525 | 1.455 | 1.384 | 1.463 | 1721 | |||||
1c | R2 = CHCl2, R3 = H | 1.414 | 1.468 | 1.524 | 1.456 | 1.385 | 1.459 | 1726 | |||||
1d | 1.338 | 1.338 | 1.400 | 1.338 | 1.338 | 1.400 | 0.985 | 0.010 | 0.005 | — | 1617 | ||
1e | 1.400 | 1.367 | 1.364 | 1.374 | 1.303 | 1.469 | 0.591 | 0.087 | 0.322 | 1743 | 1645 | ||
2 | R2 = CH3, R3 = H | 1.406 | 1.388 | 1.349 | 1.391 | 1.396 | 1.456 | 0.466 | 0.199 | 0.335 | 1721 | 1695 | |
3 | R2 = CH2Cl, R3 = H | 1.421 | 1.396 | 1.346 | 1.392 | 1.396 | 1.452 | 0.414 | 0.209 | 0.376 | 1738 | 1705 | |
4 | R2 = CHCl2, R3 = H | 1.440 | 1.419 | 1.351 | 1.391 | 1.389 | 1.442 | 0.408 | 0.251 | 0.341 | 1741 | 1703 | |
5 | R2 = CH3, R3 = Cl | 1.420 | 1.390 | 1.351 | 1.390 | 1.394 | 1.450 | 0.470 | 0.210 | 0.320 | 1726 | 1686 | |
6 | R2 = CH2Cl, R3 = Cl | 1.435 | 1.400 | 1.348 | 1.391 | 1.393 | 1.447 | 0.416 | 0.224 | 0.360 | 1745 | 1694 | |
7 | R2 = CHCl2, R3 = Cl | 1.446 | 1.406 | 1.349 | 1.389 | 1.391 | 1.443 | 0.402 | 0.234 | 0.364 | 1744 | 1690 | |
8 | R2 = CH3, R3 = NH2 | 1.415 | 1.396 | 1.358 | 1.396 | 1.391 | 1.448 | 0.512 | 0.234 | 0.254 | 1734 | 1695 | |
9 | R2 = CH2Cl, R3 = NH2 | 1.431 | 1.407 | 1.354 | 1.396 | 1.390 | 1.445 | 0.444 | 0.250 | 0.306 | 1748 | 1711 | |
10 | R2 = CHCl2, R3 = NH2 | 1.445 | 1.414 | 1.356 | 1.395 | 1.389 | 1.438 | 0.440 | 0.268 | 0.292 | 1750 | 1703 | |
11 | R2 = CH3, R3 = CH3 | 1.411 | 1.401 | 1.354 | 1.392 | 1.392 | 1.451 | 0.487 | 0.225 | 0.288 | 1726 | 1693 | |
12 | R2 = CH2Cl, R3 = CH3 | 1.427 | 1.411 | 1.351 | 1.393 | 1.391 | 1.447 | 0.429 | 0.239 | 0.332 | 1742 | 1708 | |
13 | R2 = CHCl2, R3 = CH3 | 1.440 | 1.419 | 1.351 | 1.391 | 1.389 | 1.442 | 0.408 | 0.251 | 0.341 | 1741 | 1703 | |
14 | R2 = CH3, R3 = CH2CH2CH2Cl | 1.413 | 1.404 | 1.355 | 1.392 | 1.390 | 1.450 | 0.488 | 0.229 | 0.282 | 1723 | 1692 | |
15 | R2 = CH2Cl, R3 = CH2CH2CH2Cl | 1.428 | 1.414 | 1.352 | 1.392 | 1.390 | 1.446 | 0.432 | 0.243 | 0.325 | 1740 | 1705 | |
16 | R2 = CHCl2, R3 = CH2CH2CH2Cl | 1.441 | 1.422 | 1.352 | 1.391 | 1.387 | 1.442 | 0.407 | 0.255 | 0.339 | 1740 | 1700 | |
17 | R2 = CH3, R3 = CH2CH2CH2NH2 | 1.411 | 1.403 | 1.356 | 1.390 | 1.390 | 1.451 | 0.495 | 0.229 | 0.276 | 1715 | 1683 | |
18 | R2 = CH2Cl, R3 = CH2CH2CH2NH2 | 1.428 | 1.415 | 1.350 | 1.393 | 1.390 | 1.446 | 0.423 | 0.240 | 0.337 | 1740 | 1705 | |
19 | R2 = CHCl2, R3 = CH2CH2CH2NH2 | 1.441 | 1.423 | 1.351 | 1.391 | 1.388 | 1.441 | 0.400 | 0.253 | 0.347 | 1739 | 1699 | |
20 | R2 = CH3, R3 = CH2CH2CH2NHC(NH)NH2 | 1.412 | 1.405 | 1.355 | 1.392 | 1.390 | 1.450 | 0.487 | 0.229 | 0.284 | 1723 | 1691 | |
21 | R2 = CH2Cl, R3 = CH2CH2CH2NHC(NH)NH2 | 1.428 | 1.414 | 1.351 | 1.393 | 1.390 | 1.446 | 0.427 | 0.243 | 0.330 | 1741 | 1706 | |
22 | R2 = CHCl2, R3 = CH2CH2CH2NHC(NH)NH2 | 1.441 | 1.423 | 1.352 | 1.391 | 1.387 | 1.441 | 0.404 | 0.256 | 0.340 | 1740 | 1700 |
In the first part of this study, we carried out a detailed analysis of the geometrical parameters of the pyrrolopyrazinone derivatives (Scheme
In the second part of this study, analysis of the aromaticity of the pyrrolopyrazinone derivatives was carried out to find the possible interplay between the existence of the hydrogen bonds and aromaticity of the heterocyclic rings. Aromaticity is a topic of scientific interest in the various areas of pyrrole derivative investigation. Numerous aromaticity concepts have been proposed to describe and evaluate this phenomenon. Criteria for establishing aromaticity of various species analyzed have been divided [
In general, the purpose of this study is to extend knowledge of physicochemical properties of pyrrolopyrazinones including spectroscopic properties of both heterocyclic rings. Theoretical analysis is performed using B3LYP/aug-cc-pVDZ calculations, the quantum theory of atoms in molecules (QTAIM) approach, and the natural bond orbital (NBO) method. The intramolecular C=O⋯H–C hydrogen bonds in the pyrrolopyrazinone molecules (1–22) are analyzed in terms of the NBO method, and orbital-orbital overlapping energy, ΔEn→
The infrared spectrum of peramine 20 was investigated at room temperature in KBr pellets containing dispersed compounds. The FT-IR absorption spectrum was recorded in the range between 400 and 4000 cm−1 with a Nicolet Magna-IR 550 Series II instrument.
The calculations were performed with the Gaussian 09 sets of codes [
Gaussian output wfn files were used as inputs for the AIM2000 [
Particularly, for the C-H...O hydrogen bond, these are the characteristics of the H...O bond critical point and the properties of the ring critical point that exist within the ring closed by the C=O⋯H–C intramolecular hydrogen bond. Relationships between topological parameters at the critical point are given by [
Kinetic electron energy density GBCP has a positive value, whereas potential electron energy density VBCP has a negative value. If the absolute value of VBCP is two times greater than the GBCP value, the Laplacian
The NBO method [
The HOMA index is expressed by
The Pauling bond number and virtual CC and CN bond lengths have been applied to the HOMA aromaticity index. This allows separation of HOMA into energetic and geometric contributions for heterocyclic
According to the general formula,
Scheme
For some of the systems analyzed, the existence of C-H…O intramolecular hydrogen bonds is observed which close additional five-membered rings. We can expect here weak hydrogen bonds which are formed when the hydrogen atom is covalently bonded to a slightly more electronegative atom relative to hydrogen; the electronegativity of carbon of 2.55 is only slightly higher than that of hydrogen, that is, 2.20, according to the Pauling electronegativity scale. The identification of the A-H…B hydrogen bond is often based on the A…B distance which should be lower than the sum of their van der Waals radii; this criterion can be applied for strong and medium strength interactions. It is inadequate for weaker hydrogen bonds that are mainly electrostatic in nature. This is why the criterion of the sum of van der Waals radii is more often applied for the H…B distances; however, it is also sometimes not fulfilled for weaker interactions. The most probable interpretation is that for weak hydrogen bonds the long-range electrostatic forces act far beyond the van der Waals radii cutoff [
Table
Geometrical parameters (dH…O in Å and ∠C-H…O in degrees) corresponding to the C-H…O intramolecular contacts obtained at B3LYP/aug-cc-pVDZ; QTAIM parameters (in a.u.) corresponding to the H…O bond critical points (BCPs), electron density at BCP, ρBCP; Laplacian of electron density at BCP∇2BCP; total electron energy density at BCP; HBCP and components of the HBCP value; kinetic electron energy density, GBCP; potential electron energy density, VBCP. Designation of species according to Scheme
Compound | dH…O | ∠C-H…O | dC-H | ρRCP | ∇2ρRCP | ρBCP | ∇2ρBCP | HBCP | V | G | ρBCP (C-H) | |
---|---|---|---|---|---|---|---|---|---|---|---|---|
(Å) | (°) | (Å) | (a.u.) | |||||||||
2 | R2 = CH3, R3 = H | 2.26 | 106.10 | 1.09 | 0.2844 | |||||||
3 | R2 = CH2Cl, R3 = H | 2.27 | 103.44 | 1.09 | 0.2899 | |||||||
4 | R2 = CHCl2, R3 = H | 2.17 | 107.67 | 1.09 | 0.0213 | 0.1078 | 0.0217 | 0.0840 | 0.0010 | −0.0173 | 0.0191 | 0.2925 |
5 | R2 = CH3, R3 = Cl | 2.20 | 108.38 | 1.09 | 0.0202 | 0.0925 | 0.0203 | 0.0839 | 0.0006 | −0.0197 | 0.0203 | 0.2853 |
6 | R2 = CH2Cl, R3 = Cl | 2.23 | 103.71 | 1.09 | 0.2898 | |||||||
7 | R2 = CHCl2, R3 = Cl | 2.06 | 112.13 | 1.09 | 0.0241 | 0.1231 | 0.0253 | 0.1065 | 0.0005 | −0.0255 | 0.0260 | 0.2933 |
8 | R2 = CH3, R3 = NH2 | 2.21 | 106.89 | 1.09 | 0.0203 | 0.0882 | 0.0203 | 0.0862 | 0.0008 | −0.0199 | 0.0207 | 0.2851 |
9 | R2 = CH2Cl, R3 = NH2 | 2.24 | 102.82 | 1.09 | 0.2896 | |||||||
10 | R2 = CHCl2, R3 = NH2 | 2.06 | 111.48 | 1.09 | 0.0244 | 0.1241 | 0.0255 | 0.1078 | 0.0006 | −0.0257 | 0.0263 | 0.2931 |
11 | R2 = CH3, R3 = CH3 | 2.19 | 108.16 | 1.09 | 0.0207 | 0.0939 | 0.0208 | 0.0860 | 0.0007 | −0.0202 | 0.0209 | 0.2856 |
12 | R2 = CH2Cl, R3 = CH3 | 2.23 | 102.80 | 1.09 | 0.2902 | |||||||
13 | R2 = CHCl2, R3 = CH3 | 2.04 | 111.90 | 1.09 | 0.0248 | 0.1277 | 0.0261 | 0.1108 | 0.0006 | −0.0265 | 0.0271 | 0.2938 |
14 | R2 = CH3, R3 = CH2CH2CH2Cl | 2.17 | 108.23 | 1.09 | 0.0211 | 0.0971 | 0.0213 | 0.0876 | 0.0007 | −0.0206 | 0.0213 | 0.2861 |
15 | R2 = CH2Cl, R3 = CH2CH2CH2Cl | 2.20 | 104.08 | 1.09 | 0.2905 | |||||||
16 | R2 = CHCl2, R3 = CH2CH2CH2Cl | 2.03 | 112.42 | 1.09 | 0.0257 | 0.1311 | 0.0269 | 0.1140 | 0.0006 | −0.0273 | 0.0279 | 0.2943 |
17 | R2 = CH3, R3 = CH2CH2CH2NH2 | 2.20 | 106.73 | 1.09 | 0.0207 | 0.0922 | 0.0207 | 0.0868 | 0.0008 | −0.0201 | 0.0209 | 0.2857 |
18 | R2 = CH2Cl, R3 = CH2CH2CH2NH2 | 2.19 | 104.19 | 1.09 | 0.2906 | |||||||
19 | R2 = CHCl2, R3 = CH2CH2CH2NH2 | 2.03 | 112.18 | 1.09 | 0.0252 | 0.1307 | 0.0267 | 0.1138 | 0.0006 | −0.0272 | 0.0278 | 0.2942 |
20 | R2 = CH3, R3 = CH2CH2CH2NHC(NH)NH2 | 2.17 | 108.54 | 1.09 | 0.0211 | 0.0969 | 0.0212 | 0.0873 | 0.0006 | −0.0206 | 0.0212 | 0.2860 |
21 | R2 = CH2Cl, R3 = CH2CH2CH2NHC(NH)NH2 | 2.20 | 104.91 | 1.09 | 0.2906 | |||||||
22 | R2 = CHCl2, R3 = CH2CH2CH2NHC(NH)NH2 | 2.03 | 112.36 | 1.09 | 0.0253 | 0.1311 | 0.0268 | 0.1140 | 0.0006 | −0.0273 | 0.0279 | 0.2942 |
The phenomenon which influences the geometry of C-H…O=C interactions is the acidity of the proton donating C-H group [
Replacement of the H atom from the group R2 = CH3 by Cl results in a reduction in the H…O distance [
For all molecules, under consideration (2–22), the H…O distances are within the range acceptable for intramolecular H-bonds. To find whether these H…O contacts may be classified as attractive hydrogen bonds, additional QTAIM and NBO analyses were performed here.
The quantum theory of atoms in molecules, QTAIM [
Molecular graphs (representation of bonding interactions according to QTAIM results) of the system analyzed in this study: 23 (a), 22 (b), and 21 (c). The dotted line corresponds to a bond path.
There is a bond path connecting C=O and C-H groups for systems 4, 7, 10, 13, 16, 19, 22, that is, for structures where R2 = CHCl2 (X=Cl, Y=Cl according to Table
Table
The largest electron density at the proton-acceptor (H…O) bond critical point is observed for 16 (R2 = CHCl2, R3 = (CH2)3Cl), peramine derivative 19 (R2 = CHCl2, R3 = (CH2)3NH2), and 22 (R2 = CHCl2, R3 = (CH2)3NHC(NH)NH2), 0.0269, 0.0267, and 0.0268 a.u., respectively.
Figure
For the sample 21 where R2 = CH2Cl, the Cl…H distance is 2.81 Å, and the ∠C-H…O bond angle is 104.91°. In such a case, there is not a bond path connecting carbonyl oxygen with hydrogen of the R2 group (Figure
It is seen that systems with R2 = CHCl2 correspond to the strongest interactions since it is also supported by other results collected in Table
The correlation between the length of the hydrogen bond and electron density at the corresponding bond critical point,
Correlation between electron density at the H-bond critical points ρBCP (in a.u.) and the H…O distance (in Å) was calculated at the B3LYP/aug-cc-pVDZ level. (4, 7, 10, 13, 16, 19, and 22; R2 = CHCl2) (5, 8, 11, 14, 17, and 20; R2 = CH3).
The properties of the ring critical point which is observed for the intramolecular hydrogen bonds often correlate with other measures of HB strength. It is noted that for the HBs analyzed here there is a linear correlation between the
According to the latest studies on HB description, HB strength is related to the kinetic energy of electron density at the BCP and the decrease of potential energy and decrease of total electron energy density at the BCP [
The NBO method is a useful tool to analyze intra- and intermolecular interactions. There are two effects that are often attributed to A-H...B hydrogen bond formation: a hyper conjugative effect of A-H bond weakening and rehybridization-promoted A-H bond strengthening [
In NBO theory, a donor-acceptor picture of H-bonding is based on overlap-type ionic resonance. The resonance hybrid O…H-C ↔ OH+…C− corresponds to a two-electron intermolecular donor-acceptor interaction of the form nO→
Table
Occupancy of natural orbitals (NBO), corresponding to the C-H…O intramolecular contacts, obtained at B3LYP/aug-cc-pVDZ; E(2) means energy of hyperconjugative interactions; Ei-Ej is energy difference between donor and acceptor NBO orbitals. Designation of species according to Scheme
Compound | Acceptor (A) |
Donor (B) |
E(2)AB |
Ei-Ej | ||||
---|---|---|---|---|---|---|---|---|
Type | Occupancy | Type | Occupancy | Hybrid (O) | ||||
2 | R2 = CH3, R3 = H | BD |
0.00944 | LP(2) | 1.85498 | s (0.00%), p 1.00 (99.67%), and d 0.00 (0.33%) | 1.32 | 0.67 |
3 | R2 = CH2Cl, R3 = H | BD |
0.01785 | LP(2) | 1.85014 | s (0.00%), p 1.00 (99.66%), and d 0.00 (0.34%) | 1.37 | 0.65 |
4 | R2 = CHCl2, R3 = H | BD |
0.03173 | LP(2) | 1.84338 | s (0.01%), p 1.00 (99.65%), and d 0.00 (0.34%) | 2.87 | 0.67 |
5 | R2 = CH3, R3 = Cl | BD |
0.01231 | LP(2) | 1.84837 | s (0.01%), p 1.00 (99.66%), and d 0.00 (0.33%) | 1.63 | 0.68 |
6 | R2 = CH2Cl, R3 = Cl | BD |
0.01943 | LP(2) | 1.84368 | s (0.01%), p 1.00 (99.64%), and d 0.00 (0.34%) | 1.71 | 0.66 |
7 | R2 = CHCl2, R3 = Cl | BD |
0.03248 | LP(2) | 1.84651 | s (0.00%), p 1.00 (99.66%), and d 0.00 (0.34%) | 2.65 | 0.67 |
8 | R2 = CH3, R3 = NH2 | BD |
0.01129 | LP(2) | 1.85463 | s (0.00%), p 1.00 (99.67%), and d 0.00 (0.33%) | 1.48 | 0.68 |
9 | R2 = CH2Cl, R3 = NH2 | BD |
0.01876 | LP(2) | 1.85009 | s (0.00%), p 1.00 (99.66%), and d 0.00 (0.34%) | 1.56 | 0.66 |
10 | R2 = CHCl2, R3 = NH2 | BD |
0.03187 | LP(2) | 1.84175 | s (0.01%), p 1.00 (99.65%), and d 0.00 (0.34%) | 1.57 | 0.64 |
11 | R2 = CH3, R3 = CH3 | BD |
0.01110 | LP(2) | 1.85514 | s (0.00%), p 1.00 (99.67%), and d 0.00 (0.33%) | 1.74 | 0.68 |
12 | R2 = CH2Cl, R3 = CH3 | BD |
0.01830 | LP(2) | 1.85056 | s (0.00%), p 1.00 (99.66%), and d 0.00 (0.34%) | 1.19 | 0.66 |
13 | R2 = CHCl2, R3 = CH3 | BD |
0.03176 | LP(2) | 1.84328 | s (0.01%), p 1.00 (99.65%), and d 0.00 (0.34%) | 1.41 | 0.64 |
14 | R2 = CH3, R3 = CH2CH2CH2Cl | BD |
0.01154 | LP(2) | 1.85466 | s (0.00%), p 1.00 (99.67%), and d 0.00 (0.32%) | 1.77 | 0.68 |
15 | R2 = CH2Cl, R3 = CH2CH2CH2Cl | BD |
0.01891 | LP(2) | 1.85004 | s (0.00%), p 1.00 (99.66%), and d 0.00 (0.34%) | 1.86 | 0.66 |
16 | R2 = CHCl2, R3 = CH2CH2CH2Cl | BD |
0.03221 | LP(2) | 1.85237 | s (0.01%), p 1.00 (99.66%), and d 0.00 (0.33%) | 1.89 | 0.65 |
17 | R2 = CH3, R3 = CH2CH2CH2NH2 | BD |
0.01102 | LP(2) | 1.85699 | s (0.00%), p 1.00 (99.67%), and d 0.00 (0.32%) | 1.53 | 0.68 |
18 | R2 = CH2Cl, R3 = CH2CH2CH2NH2 | BD |
0.01866 | LP(2) | 1.85040 | s (0.00%), p 1.00 (99.66%), and d 0.00 (0.34%) | 1.62 | 0.66 |
19 | R2 = CHCl2, R3 = CH2CH2CH2NH2 | BD |
0.03193 | LP(2) | 1.84319 | s (0.01%), p 1.00 (99.65%), and d 0.00 (0.34%) | 1.47 | 0.65 |
20 | R2 = CH3, R3 = CH2CH2CH2NHC(NH)NH2 | BD |
0.01143 | LP(2) | 1.85483 | s (0.00%), p 1.00 (99.67%), and d 0.00 (0.32%) | 1.83 | 0.68 |
21 | R2 = CH2Cl, R3 = CH2CH2CH2NHC(NH)NH2 | BD |
0.01838 | LP(2) | 1.85023 | s (0.00%), p 1.00 (99.66%), and d 0.00 (0.34%) | 1.92 | 0.66 |
22 | R2 = CHCl2, R3 = CH2CH2CH2NHC(NH)NH2 | BD |
0.03209 | LP(2) | 1.84293 | s (0.01%), p 1.00 (99.65%), and d 0.00 (0.34%) | 1.95 | 0.65 |
The s-character for the Lewis acid C-H increases in the order R2 = CH3, R2 = CH2Cl, R2 = CHCl2. For example, for 2, 3, and 4, C-H acceptor occupancy is equal to 0.0094, 0.0178, and 0.0317, respectively. This effect was observed previously for the hydrogen bonding complexes [
NBO results enable us to suggest the presence of an attractive C=O⋯H-C intramolecular interactions for all compound under study. Contrary to expectations, there is no QTAIM evidence of the existence of the hydrogen bond, 3, 6, 9, 12, and 15 (where R2 = CH2Cl), since the H…O bond path is not observed.
There was a similar earlier finding for the intramolecular dihydrogen bonds where for some systems the NBO method showed an orbital-orbital overlap typical for the intramolecular interaction while QTAIM did not show the corresponding bond path [
It is noted that the results presented here are partly consistent with AIM analysis. The greatest values of electron density at the H...O bond critical point are observed for moieties where R2 = CHCl2 (Table
Interestingly, the lone pair electrons localized on the oxygen atom in the systems where R2 = CHCl2 point toward the C-H hydride atom as seen in Figure
NBO overlap interaction surface plot for the bay region of pyrrolopyrazinones 22 (R2 = CHCl2) and 20 (R2 = CH3) showing stabilizing donor-acceptor nO→
It seems most likely that the changes observed in the H-bonding can be due to the steric repulsion between oxygen and chlorine atoms. The presence of H-bond depends on geometrical arrangement of the oxygen and hydrogen atoms determined by its repulsion. In R2 = CHCl2, two chlorine atoms are forced to be in the anticlinal configuration with respect to oxygen. Such behavior minimizes repulsion, and therefore the H atom of the CHCl2 group is in a synperiplanar configuration that is favorable for H-bonding.
In R2 = CH2Cl, the minimal repulsion is present in the antiperiplanar configuration of the oxygen and chlorine atom. This phenomenon forces the synclinal conformation of two hydrogen atoms of R2 with respect to O atom. It is much less favorable for H-bond formation between C=O and R2 = CH2Cl.
Palusiak et al. [
The HOMA indices calculated for pyrrole (1), 3,4-dihydropyrrolopyrazinones (1a–c), pyrazine (1d), 2-oxopyrazine (1e), and pyrrolopyrazinones (2–22) are shown in Table
The HOMA index of pyrrole (1) is 0.833, whereas local HOMAs of 3,4-dihydropyrrolopyrazinones (1a–c) range from 0.876 to 0.885. The aromaticity of the pyrrole ring in 2–22 moieties varies between 0.848 and 0.905 HOMA units. It is seen that the HOMAs of the pyrrole ring for structures 1c, 4, 7, 10, 13, 16, 19, and 22 where R2 = CHCl2 are higher than those for structures 1a, 2, 5, 8, 11, 14, 17, and 20, and 1b, 3, 6, 9, 12, 15, 18, and 21 where R2 = CH3 or CH2Cl, respectively. For instance, the HOMA value for the pyrrole ring of peramine (20) where R2 = CH3 is 0.865, for the chloromethylene derivative (21) where R2 = CH2Cl is 0.869, and for the dichloromethylene derivative (22) where R2 = CHCl2 is 0.877 a.u.
The local HOMA indices of the pyrrole ring for 3,4-dihydropyrrolopyrazinones 1a, 1b, and 1c are higher than those of pyrrolopyrazinone 2, 3, and 4 (Table
It is worth mentioning that the so-called Clar’s rules represent a qualitative description of the aromatic character of a particular ring in a molecule of polycyclic species. These rules classify rings according to their
It is concluded based on the results from Table
The HOMA index of pyrazine (1d) [
It is worth noting that the opposite relationship is observed for the local HOMA aromaticity index of the pyrrole ring; it is greater for R2 = CHCl2 than for R2 = CH3 or R2 = CH2Cl.
Some attention was paid previously to the intermolecular interactions affecting aromaticity of certain phenol derivatives [
The electron-withdrawing substituents, such as –CHCl2, lead to a local EN increase for pyrazinone that consequently results in the decrease in the corresponding local HOMA index. The lower local aromaticity of the pyrazinone ring may result from the methyl group electron-withdrawing properties that increase if hydrogen atoms are substituted by chlorine atoms. It is also noted, however, that the increase of stability of the other ring, pyrrole, is expressed in the increase of the corresponding local HOMA index. In other words, an increase in the aromaticity of one ring leads to lower aromaticity of the other ring. This result is consistent with the earlier findings for pyrrole and
Moreover, it is worth noting that the HOMA aromaticity index for the pyrazine ring, 1d, of 0.985 is greater than that calculated for 2-oxo-pyrazine, 1e, of 0.591. This may be compared with the pyrazinone ring HOMA values for 2, 3, and 4, equal to 0.466, 0.414, and 0.408, respectively. An analogous situation is observed for residual pairs of pyrrolopyrazine moieties.
These observations can be concluded in the following way. The C-H…O contact is shorter with higher local HOMA aromaticity of the pyrrole ring and lower HOMA aromaticity of the pyrazinone ring. These interrelated changes may be explained by a decrease in bond length alternation in the pyrrole ring confirmed by a decrease in GEO increments and a decrease in resonance energy of the pyrazinone ring confirmed by an increase in the EN increment to HOMA.
Table
H-bond formation affects the stretching band of the A-H bond as well as the stretching vibrational mode of the proton-accepting center, that is, the C=O group in this study. Current computational studies reveal that the frequency of the C=O stretching mode of systems 2, 3, and 4 for which R2 = CH3, R2 = CH2Cl, and R2 = CHCl2 ranges from 1669 cm−1 in 2 (R2 = CH3) without intramolecular C-H…O interactions to 1689 cm−1 for system 4 (R2 = CHCl2).The frequency of the C=O stretching mode of systems 2, 5, 8, 11, 14, 17, and 20 for which R2 = CH3 ranges from 1674 cm−1 in system 5 to 1664 cm−1 in system 17.
The frequency of the C=O stretching mode of systems 3, 6, 9, 12, 15, 18, and 21 for which R2 = CH2Cl ranges from 1696 cm−1 in system 9 to 1686 cm−1 in system 3.
The formation of the hydrogen bond leads to an electron density shift from the Lewis base to the Lewis acid unit; for the C-H…O interactions analyzed here; from the lone pairs of oxygen (C=O group) to the C-H proton donor. It is expressed as the n(O)→
Figure
Experimental (a, b) and calculated (c, d) IR spectra (B3LYP/aug-cc-pVDZ level of theory) of peramine 20 (R2 = CH3), 21 (R2 = CH2Cl), and 22 (R2 = CHCl2) according to Scheme
It has been found on the basis of the previous study [
When R2 = CHCl2, an intramolecular CH…O=C hydrogen bond is formed. This effect causes the shift of ν
It seems that νC=O increases with the C-H…O=C distance decrease (Table
Pyrrolo[1,2-a]pyrazin-1(
For the pyrrolopyrazinone derivatives analyzed here, formation of the intramolecular C-H…O hydrogen bond is observed. In general, geometrical and NBO criteria confirm the existence of such interactions for all systems since the H…O distances for all of them are shorter than the corresponding sum of hydrogen and oxygen van der Waals radii as well as for all species in which
The changes observed in the H-bonding can be due to the steric repulsion between oxygen and chlorine atoms. The presence of H-bond depends on the geometrical arrangement of the oxygen and hydrogen atoms determined by its repulsion.
The aromaticity changes are discussed here in terms of the HOMA index and its EN and GEO components. The shortest C-H…O=C contact is related to a higher νC=O value.
The authors declare that they have no conflicts of interest.
Calculations were carried out in the Warsaw Supercomputer Center (ICM) (G53-7).