Dual Photochemistry of Benzimidazole

Abstract

Monomers of benzimidazole trapped in an argon matrix at 15 K were characterized by vibrational spectroscopy and identified as 1H-tautomers exclusively. The photochemistry of matrix-isolated 1H-benzimidazole was induced by excitations with a frequency-tunable narrowband UV light and followed spectroscopically. Hitherto unobserved photoproducts were identified as 4H- and 6H-tautomers. Simultaneously, a family of photoproducts bearing the isocyano moiety was identified. Thereby, the photochemistry of benzimidazole was hypothesized to follow two reaction pathways: the fixed-ring and the ring-opening isomerizations. The former reaction channel results in the cleavage of the NH bond and formation of a benzimidazolyl radical and an H-atom. The latter reaction channel involves the cleavage of the five-membered ring and concomitant shift of the H-atom from the CH bond of the imidazole moiety to the neighboring NH group, leading to 2-isocyanoaniline and subsequently to the isocyanoanilinyl radical. The mechanistic analysis of the observed photochemistry suggests that detached H-atoms, in both cases, recombine with the benzimidazolyl or isocyanoanilinyl radicals, predominantly at the positions with the largest spin density (revealed using the natural bond analysis computations). The photochemistry of benzimidazole therefore occupies an intermediate position between the earlier studied prototype cases of indole and benzoxazole, which exhibit exclusively the fixed-ring and the ring-opening photochemistries, respectively.

Scheme 1. Photoreactivity of Benzoannulated Azoles in Solution⁻

Chart 1. Molecular Structures of Benzoxazole, Benzimidazole, and Indole

Scheme 2. Photoinduced Reactivity of Monomeric Benzoxazole^,

Note color codes for the irradiations at different wavelengths.

Scheme 3. Photoinduced Reactivity of Monomeric Indole and 7-Azaindole^,,

Numbering of heavy atoms of the starting compounds and ring position 3 of the photoproducts are shown in red.

Figure 1

(a) Experimental IR spectrum of benzimidazole monomers isolated in an argon matrix at 15 K. (b) Black trace—simulated IR spectrum of 1H-BzIm computed at the B97-1/def2-TZVP level of theory in harmonic approximation. See the Experimental Section for details of simulation. See Figure S2 for the linear fit and determination of the scaling factor. Red trace—simulated spectrum of the first overtones (computed anharmonic frequencies unscaled). The bands marked with one and two asterisks (in both frames) are, respectively, assigned to the fundamental and the first overtone transitions of the NH out-of-plane bending γ(NH) mode.

Figure 2

Changes of the IR spectra of BzIm isolated in an Ar matrix at 15 K during a sequence of irradiations, initially at λ = 277 nm (blue palette) and subsequently at λ = 248 nm (brown palette). The bands with maxima near 1560 and 1548 cm^–1 were assigned to species A and B, respectively, photogenerated from 1H-BzIm. The dashed lines represent the peak intensities of A and B corresponding to two photostationary states.

Figure 3

(a) Experimental difference IR spectrum showing changes upon UV irradiation at λ = 260 nm of BzIm isolated in an Ar matrix at 15 K. The downward bands are due to consumed species assigned to 1H-BzIm (truncated), and the upward bands are due to the photoproduced species A and B, distinguished based on further photo-transformations (see discussion below). The bands near 1600 cm^–1 marked with w (dimmed) correspond to matrix-isolated monomeric water. (b) Simulated IR spectra of 1H-BzIm (black line), 4H-BzIm (blue line), and 6H-BzIm (red line) computed at the B97-1/def2-TZVP level of theory. The theoretical vibrational frequencies were scaled by 0.983, and the IR intensity of 1H-BzIm was multiplied by −1.

Figure 4

(a) Experimental difference IR spectrum showing changes upon UV irradiation at λ = 330 nm, subsequent to the initial irradiation at λ = 260 nm of BzIm isolated in an Ar matrix at 15 K. The downward bands are due to consumed 4H-BzIm (blue circles); the upward bands are due to photoproduced 6H-BzIm (red squares) and 1H-BzIm (black triangles). (b) Simulated IR spectra of 1H-BzIm (black line), 4H-BzIm (blue line), and 6H-BzIm (red line) computed at the B97-1/def2-TZVP level. The theoretical vibrational frequencies were scaled by 0.983, and the IR intensity of 4H-BzIm was multiplied by −1.

Figure 5

(a) Characteristic fragment of the IR spectra of benzimidazole isolated in an Ar matrix at 15 K: before irradiations (gray line) and after UV irradiations at 260 nm (blue line), 330 nm (red line), and 283 nm (green line). (b) B97-1/def2-TZVP-computed harmonic wavenumbers and IR intensities for putative isocyano photoproducts. Respective structures are shown in Chart 2. The computed frequencies were scaled as discussed in the Computational Section.

Figure 6

(a) Changes in the spectrum of matrix-isolated BzIm after 2 min of irradiation at λ = 248 nm. The negative (truncated) band is due to the BzIm precursor. Positive bands are due to the photoproduct. (b) Simulated IR difference spectrum computed at the B97-1/def2-TZVP level. The positive bands are due to ICA 12 (note that computed IR intensities of 12 were scaled by 0.25, which makes it clear that conversion from 11 to 12 is not quantitative). The negative (computed IR intensity scaled by −1, truncated) band is due to 1H-BzIm 11. All computed frequencies in this range were scaled by 0.955.

Chart 2. Structures of Benzimidazole and its Isonitrile (Isocyano) Derivatives

Figure 7

Left: structure of the benzimidazolyl radical optimized at the UB97-1/def2-TZVP level showing NRT bond orders (purple, only values higher than 1.0 included) and non-bonding orbital populations (green, only values higher than 0.02 included). Numbering of the heavy atoms is shown in red. Right: spin density surface (isovalue ± 0.01 e) for the benzimidazolyl radical. Green color stands for alpha spin density (“+” sign) and yellow for beta spin (“–” sign). Element colors: H—white; C—gray; and N—blue. The values near the heavy atoms correspond to the calculated atomic natural spin density values.

Figure 8

Potential energy profiles along the intrinsic reaction coordinates (IRCs) for the H-shifts between neighboring heavy atoms in the benzimidazole system computed at the B97-1/def2-TZVP level in non-mass-weighted (Cartesian) coordinates. The absolute electronic energy of the 1H-BzIm tautomer was taken as the relative zero. Horizontal solid lines represent the zero-point vibrational energy (ZPVE) levels of the higher-energy tautomer in each pair. Dashed lines represent the barrier widths for H-atom tunneling at the ZPVE level. See Table 1 for the graphical representation of the prototropic tautomers and for their energies.

Figure 9

IRC profiles for the H-shifts around the six-membered ring (the migrating H atom is marked in red) computed at the B97-1/def2-TZVP level in non-mass-weighted (Cartesian) coordinates. The energy of 1H was set as the relative zero. The syn-NH and anti-NH imino isomers of 2-isocyanoaniline are shown near the IRC profiles, along with the atom numbering. The ring positions 4-, 6-, 7-, and 9- correspond to the meta-(NC), meta-H, ortho-H, and ortho-(NC) positions relative to the NH group, respectively. The structures and energies of the isomers resulting from recombination of an H-atom with radicals 13 and 14 at different ring positions are summarized in Table S7.

Scheme 4. Summary of Dominant Concurrent Photochemistries of Monomeric Benzimidazole Isolated in an Argon Matrix at 15 K

Molecules 12–20 in the left panel (“ring-opening”), with the isocyano groups shown in red, were identified as a family; the two molecules in the right panel (“fixed-ring”) surrounded by rectangles, 22 and 23, were characterized by at least 15 IR bands each. Note color codes for irradiations at different wavelengths. The black dashed arrows correspond to the recombination of the radical pairs.