Synthesis, spectral studies, antimicrobial and insect antifeedant potent keto oxiranes

2.1 Materials and methods

All chemicals used were purchased from Sigma–Aldrich and E-Merck chemical company. Melting points of all oxiranes have been determined in open glass capillaries on Mettler FP51 melting point apparatus and are uncorrected. Infrared spectra (KBr, 4000–400 cm⁻¹) have been recorded on AVATAR-300 Fourier transform spectrophotometer. INSTRUM AV300 NMR spectrometer operating at 300 MHz has been utilized for recording ¹H NMR spectra and 75.46 MHz for ¹³C spectra in CDCl₃ solvent using TMS as internal standard. Electron impact (EI) (70 eV) and chemical ionization mode FAB⁺ mass spectra have been recorded with a JEOL JMS600H spectrometer.

2.2 Synthesis of substituted biphenyl chalcones

All substituted styryl biphenyl ketones were synthesized by the literature procedure (Thirunarayanan and Vanangamudi, 2006).

2.3 Synthesis of biphenyl keto oxiranes (Thirunarayanan and Vanangamudi, 2010)

Appropriate mixture of substituted styryl biphenyl ketones (0.10 mmol) and a chiral quaternary ammonium bromide–PF₆ catalyst (6 mg, 0.003 mmol, 3 mol%) in toluene (3 mL) was added to 15% aqueous sodium hypochlorite (NaOCl, 0.15 mL) and the mixture was stirred for 14 h (minimum 10 h) at 0 °C under inert atmosphere (Scheme 1). The resulting mixture was diluted with water and the organic phase was separated. Using dichloromethane, the aqueous medium was extracted and the same was repeated thrice. Then the resulting organic extract was dried using anhydrous sodium sulfate. After evaporating the solvent, the resulting product was purified using flash column chromatography on silica gel (ethyl acetate/hexane) as eluent afforded the epoxide. An optical purity of the epoxy ketone was determined by chiral stationary phase HPLC analysis. The spectral data are presented in Table 1.

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Scheme 1

Synthesis of epoxy ketones.

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3.1 IR spectral study

The synthesized oxiranes in the present study are shown in Scheme 1. The infrared ν_CO and ν_C–O–C stretching frequencies (cm⁻¹) of these oxiranes were recorded and are presented in Table 1. These data have been correlated with Hammett substituent constants and Swain–Lupton constants (Swain and Lupton, 1968). In this correlation the structure parameter Hammett equation employed is as shown in the following equation:

The results of statistical analyses are shown in Table 2. From Table 2, it is evident that all constants produce satisfactory correlation with carbonyl stretching frequencies except for some substituents such as 3-Br, 3-NH₂, 4-NH₂ and 4-OH. When these substituents are included in the regression, they reduced the correlation considerably. All correlations gave positive ρ values. This shows that a normal substituent effect operates in all keto epoxides. The F parameter is satisfactorily correlated with carbonyl frequencies of all epoxides without deviation with respect to any substituent. Similarly the multi-regression analysis of these carbonyl frequencies with Swain–Lupton parameters are found to correlate satisfactorily and the correlation equations are,

The assigned C–O–C stretching frequencies (cm⁻¹) have been correlated with Hammett substituent constants, F and R parameters using single regression analysis. The results of statistical analyses are presented in Table 2. The Hammett σ_R inductive and F parameters are found to correlate satisfactorily with C–O–C (cm⁻¹) frequencies excluding 3-Br and 3-Cl substituents in all keto-epoxides along with negative ρ values evidencing reversal substituent effects operating in all oxiranes. The Hammett σ, σ⁺ and σ_I constants and the resonance parameters failed in correlation and the sigma constants gave positive ρ values. This is due to the resonance and polar effects of the substituents, incapable for predicting the reactivity on the C–O–C frequency along with the conjugative structure in Fig. 1. Some of the single parameter correlations also fail in these regression analyses. While seeking the multi-regression analysis with Swain–Lupton constants (Swain and Lupton, 1968) correlation is found to be satisfactory. The multi-parameter equations are as,

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Figure 1

Resonance-conjugative structure of epoxide.

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3.2 ¹H NMR spectral study

The ¹H NMR spectra of 13 oxiranes under investigation have been recorded in deuterochloroform solution employing tetramethylsilane (TMS) as internal standard. The signals of the oxirane ring protons have been assigned. They were calculated as AB or AA′ BB′ systems, respectively. The chemical shifts of H_α are at lower field than those of H_β in this series of keto-epoxides due to higher deshielding of H_α and is nearer to carbonyl group. These protons gave an AB pattern and the β-proton doublet in most cases was well separated from the signals of the aromatic protons. The assigned chemical shifts of the ring protons are presented in Table 1.

In nuclear magnetic resonance spectra, the proton or the ¹³C chemical shifts (δ) depend on the electronic environment of the nuclei concerned. These shifts have been correlated with reactivity parameters. Thus the Hammett equation may be used in the form as

The assigned H_α and H_β proton chemical shifts (ppm) of oxirane ring have been correlated with various Hammett sigma constants. The results of statistical analyses are presented in Table 3. All the attempted correlations involving substituent parameters gave only positive ρ value in the case of oxirane ring H_α. This shows that the normal substituent effect operates in all chalcones. The H_α proton chemical shifts poorly correlated with Hammett substituent constants. This is due to the reason stated earlier with the conjugative structure in Fig. 1. In the correlations of H_β proton chemical shifts with Hammett σ constants, F and R parameters are satisfactory excluding 4-OH and 4-NO₂ substituents in phenyl ring.

From Table 3, the r values show that the reactivity of the substituents on H_α is lesser than that of H_β in all epoxy ketones. This is in contrast to the findings of Solcaniova and Toma (1980) in the case of unsaturated ketones. In fact the extent of transmission of electrical effect is almost absent from the substituents to H_α and partially sensitive on H_β in the present investigation. It has been the observation of Solcaniova et al. (1976) that the chemical shifts of the β-protons do not correlate with any type of substituent parameters in their chalcones series. The application of Swain–Lupton (Swain and Lupton, 1968) treatment to the relative chemical shifts of H_α and H_β with F and R values is successful with either resonance, inductive or F and R parameter generating the multi-regression equations as,

3.3 ¹³C NMR spectra

Organic chemists and scientists (Annapoorna et al., 2002; Dhami and Stothers, 1963a,b; Thirunarayanan et al., 2007) have made extensive study of ¹³C NMR spectra for a large number of different ketones and styrenes. They found a linear correlation of the chemical shifts of C_β carbons with Hammett σ constants in alkenes, alkynes, acid chlorides and styrenes. In the present system the chemical shifts (ppm) of carbonyl carbon and the oxirane ring carbons C_α, C_β have been assigned and are presented in Table 4. Attempts have been made to correlate the δ_CO, ${\delta }_{{\text{C}}_{\alpha }}$ and ${\delta }_{{\text{C}}_{\beta }}$ chemical shifts (ppm) with Hammett substituent constants. Field and resonance parameters with the help of single and multi-regression analysis to study the reactivity through the effect of substituents on the above frequencies.

The chemical shifts (ppm) observed for the δ_CO, ${\delta }_{{\text{C}}_{\alpha }}$ and ${\delta }_{{\text{C}}_{\beta }}$ have been correlated with Hammett constants and the results of statistical analysis are presented in Table 4. All correlations of δ_CO chemical shifts (ppm) gave fair degree of r values excluding H in all oxiranes. The Hammett σ, σ⁺ and R parameters produce positive ρ values and are evident for normal substituent effect operating in all systems. On the other hand, the Hammett σ_I, σ_R and resonance parameters show the negative ρ values giving fair degree of correlation with reversal of substituent effects. Also the multiple correlations involving either σ_I and σ_R constants or Swain–Lupton (Swain and Lupton, 1968) F and R parameters produce satisfactory correlation as shown in the equations,

The ¹³C chemical shift (ppm) values of oxirane ring carbons C_α and C_β of all keto-epoxides have been correlated with various Hammett substituent constants. The results of statistical analysis of substituent effects on carbonyl carbons are shown in Table 4. Satisfactory correlations are obtained with C_α carbon chemical shifts and produce negative ρ values with Hammett substituent constants and F and R parameters excluding H. This implies that the substituent effects are reversed. The Swain–Lupton (Swain and Lupton, 1968) parameter also correlates satisfactorily within these carbon chemical shifts. The individual correlations of C_β carbon chemical shifts with Hammett σ, σ⁺ and σ_I constants and field parameters produce satisfactory correlation excluding 2-NO₂ substituent and fail with σ_R constants and resonance factor. All correlations gave negative ρ values excluding σ_R constants. The negative ρ values imply that the substituent effect is reversed within these constants. The degree of transmission of substituent effect is found to be high in C_α chemical shifts than C_β carbon chemical shifts. Uniformly σ_I and σ_R parameters or F and R values explain substituent effects in all cases as evidenced from the correlation equations are

3.4 Microbial activities

Epoxides possess a wide range of biological activities. These multipronged activities associated with different keto epoxides are intended to examine their above activities against respective microbes, fungi and insect antifeedant activities against caster semilooper.