Photoinduced Elimination in 2,3-Dihydro-2-tert-butyl-3-benzyl-4(1H)-­quinazolinone: Theoretical Calculations and Radical Trapping Using TEMPO Derivatives

Abstract

Photochemical irradiation of 2,3-dihydro-2-tert-butyl-3-benzyl-4(1H)-quinazolinone produced 3-benzyl-4(3H)-quinazolinone through photoinduced elimination via a radical mechanism. The use of photochemical conditions such as chloroform and UV irradiation (λ = 254 nm) got the 3-benzyl-4(3H)-quinazolinone in a high yield. Some theoretical calculations were achieved to explain the mechanism and the presence of radical intermediates was confirmed by trapping with different 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) derivatives.4-Quinazolinone derivatives are important building blocks of active molecules isolated from different natural sources. 1 Their principal derivatives are 2,3-dihydro-4(1H)-quinazolinones and 4(3H)-quinazolinones. These compounds possess a wide range of useful biological activities and interesting pharmacological properties, 2 and their syntheses have been well described in the literature. 3 The use of photochemical irradiation in these compounds, however, has been less common, and only a few have been reported such as preparation of fused quinazolin-4-one derivatives, for example, luotonin A and related fused compounds through radical intermediates, 4 photodecomposition of 8-chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo[1,5-a][1,4]benzodiazepine (Midazolam) to get a 4(3H)-quinazolinone derivative, 5 and irradiation of 4-phenylquinazolin-2-ones in the presence of a hydrogen donor in order to get the reduced 3,4-dihydroquinazolin-2-ones 6 as well as the photoaddition of 4(3H)-quinazolinone derivatives to olefins. 7 In this study we analyzed the behavior of 2,3-dihydro-2-tert-butyl-3-benzyl-4(1H)-quinazolinone under UV irradiation, and theoretical calculations were developed to propose a mechanism, and trapping of the radical intermediate was achieved using TEMPO derivatives. Knowledge of these reactions could help to develop photochemically controlled reactions of other 2,3-dihydro-4(1H)-quinazolinone derivatives.Our research was focused on the preparation of starting materials following the methodology previously reported by our group 8 in which a reaction between isatoic anhydride and benzylamine in ethyl acetate at 40°C results in the corresponding aminobenzamide 1 in 90% yield. Next, the cyclocondensation of 1 with pivalaldehyde in dichloromethane and p-toluenesulfonic acid monohydrate gives 2 in 86% yield (Scheme 1).Preliminary studies rapidly led to the conclusion that it was necessary to protect the reaction from light source since this would suffer photoinduced elimination and hence reduces the yield of compound 2. The absorption spectrum of 2 ( Figure 1) presents two absorption bands at λ = 242 and 341 nm, attributed to π-π* and n-π* transitions, respectively. The fluorescence spectrum is shown in the Figure 2 and presents a maximum emission at λ = 404 nm. The quantum yield of fluorescence was measured at 25°C using quinine sulfate (H 2 SO 4 0.5 M, Φ = 0.55) as standard and employing existing equations for calculating quantum fluorescence yield;

Synthesis, Resolution and Absolute Configuration of 2,3-Dihydro-2-<i>Tert</i>-Butyl-3-<i>N</i>-Benzylquinazolin-4-One: A Possible Chiral Auxiliary for Synthesis of <i>β</i>-Amino Cyclohexancarboxylic Acid

“…Our research was focused in the preparation of starting material following the methodology previously reported by our group [11]- [13] in which a reaction between isatoic anhydride and benzylamine in ethyl acetate at 40˚C results in the corresponding aminobenzamide 10 with 90% yield. Next, cyclocondensation of 10 with pivalaldehyde in dichloromethane and p-toluenesulfonic acid monohydrate gives (±)-2,3,dihydro-4(1H)-quinazolinone rac-11 at 86% yield (Scheme 3).…”

“…It is noteworthy that was necessary to protect the reaction from light source since this would suffer photoinduced elimination and hence reduces the yield of compound 11 [11].…”

Easy synthesis of new series of pteridine analogs: di- and tetra-hydropyrimido[4,5-d]pyrimidines via 5-pyrimidinecarbaldehydes

“…A detailed explanation about the conformational search is given in the experimental section. From the low-energy conformations obtained for both diasteromers R/R and R/S we calculated the shielding tensors using the GIAO approach 33,34 from the program Gaussian 03. 35 Our study also includes the calculation of 13 C-NMR chemical shift for the diasteroisomers (R/R; R/S; S/R and S/S) by using the gauge independent atomic orbital (GIAO) approximation.…”

“…Minima were characterized through harmonic frequency analysis employing B3LYP/6-31 G(d) calculations. GIAO [33][34] (gauge independent atomic orbital) computations were carried out using B3LYP/6-31G(d) calculations. All the calculations reported here were performed using the Gaussian 03 Program.…”

“…Figure 3S shows a spatial view of the lowest-energy conformation obtained for compound 4g 2 . From the low-energy conformations obtained for both diasteromers R/R and R/S we calculated the shielding tensors using the GIAO approach 33,34 from the program Gaussian 03. 35 From the tensors we obtain the value of calculated chemical shift (calc) for each C atom of each isomer, using the following expression (Eq.…”