Synthesis and TDDFT Investigation of NewMaleimide Derivatives Bearing Pyrrole and Indole Ring

1 Industrial Technology Center of Nagasaki, 2-1303-8, Ikeda, Omura, Nagasaki 856-0026, Japan 2 Faculty of Environmental Studies, Nagasaki University, 1-14, Bunkyo-machi, Nagasaki 852-8131, Japan 3 Department of Pharmacy, Saga University Hospital, 5-1-1, Nabeshima, Saga 849-8521, Japan 4 Faculty of Pharmaceutical Sciences, Nagasaki International University, 2825-7, Huis Ten Bosch, Sasebo 859-3298, Japan


Introduction
Maleimides are widely known as active electrophilic reagents to readily react with a variety of dienes and 1,3-dipoles including azomethine ylide, carbonyl ylide and, nitorenes, leading to various heterocycles [1].We have explored the abundant synthetic potential of the new functionalized maleimides which can effectively be converted to fused pyridazine derivatives [2] and polymethine dyes [3,4].Herein we report the new series of dyes bearing push (pyrrole, indole)pull (maleimide) systems.The computational investigations are also described for their first intense electric absorption peaks using TD-DFT [5], which is widely used in electronic transition energy predictions for many molecules [6,7].

Synthesis and Electronic Spectra
A series of 4-methylthiomaleimides 1a-1c were found to undergo addition-elimination reactions with pyrrole 2a-2b and indoles 4a-4c to give new compounds 3a-3d and 5a-5g which are listed in Table 1 and the synthetic scheme is illustrated in Figure 1.

Computational Details
The computations were carried out using GAUSSIAN03 program [8].The Graphical representations of orbitals and of subtraction electron density were created by ChemCraft Software [9].
In both steps of geometry optimization and TDDFT calculations, solvent effects of ethanol were included using the nonequilibrium polarizable continuum model (PCM) [10].

A Model Compound 3a.
As a prototypical study, 3a was examined in details to assess how the set of computational parameters affect on TDDFT excitation energies.
Two-key geometrical parameters, the single bond connecting two moieties (r) and the interring torsion angle (θ), are defined in Table 1.The two parameters are consistently referred to hereafter for the remaining compounds 3b-d and 5a-g.The bond length (r = 1.405Å), considerably shorter than the standard single C-C bond length by c.a. 0.1 Å, indicates moderate electronic resonance between the two moieties.Table 2 shows the evolution of λ max as a function of basis sets used in both geometry optimizations and TDDFT calculations.As for the basis set effect on the geometry optimizations, we notice the uniform role of polarization, valence-splitting, and diffuse functions.For instance, the most extensive TDDFT using 6-311++G(2d,2p) gave λ max blue shift by 16 nm from 6-31G-to 6-31G(d,p)-optimized geometry.The valencetriple-zeta basis set 6-311G(d,p) instead of valence-double basis 6-31G(d,p) yielded 5 nm blue shift.6-31+G(d,p) basis set, augmented by single-diffuse function, shifted All DFT and TD-DFT calculations using B3LYP functional.
The optimized TDDFT scheme above-mentioned characterized the low-lying six singlet excited states for 3a, as in Table 3.The first, fourth, and sixth transitions originate from the ππ * transitions on the whole molecular plain.The first intense peak, dominantly describable with the HOMO-LUMO excitation, has large oscillator strength (f ) of 0.34.The second local excitation (LE) originates from HOMO-1 (mainly distributed on pyrrole ring) to LUMO with moderate f of 0.069.The third peak is of n − π * character with negligibly small f of 0.0002.The fourth π − π * transition derives from HOMO-3 (mainly distributed on maleimide ring) to LUMO with moderate f of 0.256.The fifth peak is of n − π * character with negligibly small f of 0.0002.The sixth n − π * transition has moderate f of 0.0281.The first computed π − π * transition at 448 (PCM-TD-DFT(B3LYP)/6-31G(d,p)) nm is ascribed to the first intense visible band at 459 nm, the fourth transition to the second band at 309 nm, and the sixth transition to the third UV band at 263 nm.The second, third, and fifth transitions with small f are thought to be hidden in the spectra.

4.2.
Other Maleimide Derivatives 3b-3d and 5a-g.Following the assessment in the previous subsection, we consistently applied PCM-TD-DFT/6-31+G(d)//PCM-DFT(B3LYP)/6-311G(d,p) to the remaining molecules 3b-3d and 5a-g.Table 4 shows the interring bond lengths and the tortional angles along with the HOMO and LUMO levels.The TDDFT-predicted first peak positions are listed in Table 5 along with the experimental ones and the statistical parameters.
3a and 3b with little intramolecular steric hindrance hold nearly planar geometry while 3c and 3d have twisted geometries because of the steric repulsion between methylpyrrole and maleimide ring.The interring bond lengths of 3a and 3b are therefore appreciably shorter than those of 3c and 3d because the π-conjugation in the molecular plain is fully restored.Concerning the theoretical λ max dependence on XC hybrid functionals, O3LYP functional (with low mixing ratio of exchange term) showed excellent agreements for planar molecules 3a and 3b but appreciably longer λ max for distorted compounds 3c and 3d.PBE0 and MPW91PW91 (with high mixing ratio of exchange term), inversely, gave worse agreement in case of 3a and 3b while a better agreement for 3c and 3d.The hybrid functionals B3PW91, B3LYP, and O3LYP gave underevaluated peaks in this order, with the peaks being blue-shifted proportional to the mixing ratio of an exact exchange term.Using the other functionals, the amplitude of λ max displacement is severely large; BLYP-, VSXC-, and HCTH-predicated peaks showed large deviations particularly for 3c and 3d.In our previous TDDFT study [13], we found some specific features and limitations of theoretical λ max for the newly prepared maleimide derivatives, where the molecules with large twist angle showed better λ max agreement owing to efficient charge separation between the two moieties while PBE0 and MPW91PW91 gave better λ max agreements than other functionals and the agreements worsen for planar compounds.All types of XC-fuctionals employed failed to reproduce hypsochromic shift of 3c and 3d in comparison with 3a and 3b.This is because theoretical λ max of nearplanar 3a and 3b are underevaluated while those of twisted 3c and 3d overvaluated, leading to this fictitious switching.
5a-5g apparently hold distorted geometry with the two π-moieties being well separated.The qualitative agreements (within 40 nm deviations between theory and experiment) were obtained using PBE0 and MPW1PW91.The theoretical peaks however were overvaluated with all the XCfunctionals, particularly for 5g using VSXC and HCTH functionals by more than 100 nm deviations.The theoretical λ max displayed systematic red-shifted tendencies in the order B3PW91<B3LYP<O3LYP for hybrid functionals, which is proportional to the mixing ratio of an exact exchange term, as in case of 3a-3d.
The relative errors and the relative standard deviations in Table 5 indicate that a qualitative agreement is between theoretical λ max and experiment for 3a, 3b, and 3c, while other molecules show a worse agreement.This is due to the considerable red-shift deviations when using VSXC and HCTH functionals which are not well optimized for twisted π-conjugated systems.

Conclusion
New maleimide derivatives bearing pyrrole and indole ring were synthesized and assessed for their UV/vis spectra experimentally and computationally.Experimental UV/vis λ max were observed in 435-504 nm.TDDFT analysis (PCM-TD-DFT / 6-31 + G(d,p)//PCM-DFT(B3LYP) / 6-311G(d,p)) for the first intense peak of the compounds was done to obtain semiquantitative agreements between experimental and theoretical λ max for the compounds.

Table 1 :
Recaptulatives of the newly synthesized compounds along with the key geometrical parameters (r, θ).

Table 2 :
λ max (in nm) dependence of 3a on the basis sets used for geometry optimization (DFT) and TD-DFT.