다양한 치환기가 붙은 Styryl 4-Methoxy-1-Naphthyl Ketone의 합성과 치환기 효과에 관한 연구

Synthesis and Substituent Effects in Substituted Styryl 4-Methoxy-1-Naphthyl Ketones

Abstract

초음파를 이용한 응축 반응을 이용하여 다양한 치환기가 붙은 4-methoxy-1-naphthyl ketone화합물들을 90% 이상의 높은 수율로 합성하였으며, 생성된 화합물물들을 미세 분석법, IR, 1H, 13C NMR 분석법 등을 이용하여 확인하였다. IR 스펙트럼에서 s-cis와 s-trans C=O stretching 모드를 확인하였으며, NMR 데이터로부터 에틸렌의 탄소와 수소에 대한 chemical shift를 확인하였다. 이러한 분광데이터를 이용하여 여러 분자들에 대한 Hammet 치환기 상수 값 들을 얻을 수 있었으며, 이들로부터 가용매 분해반응에 미치는 치환기 효과를 해석할 수 있었다.

A series of substituted styryl 4-methoxy-1-naphthyl ketones [(2E)-1-(4-methoxy-1-naphthyl)-3-phenyl-2-propen-1-ones] were synthesized using facile method of microwave assisted condensation reaction. The yield of chalcones is more than 90%. They are characterized by their physical constants, micro analysis, infrared (KBr, 4000-400 cm？1) and NMR both 1H and 13C spectral data. From infrared spectra, the s-cis and s-trans stretching vibrations of carbonyl group, from NMR spectra the ethylenic proton and carbon chemical shifts (ppm) are assigned. These spectral data are correlated with various Hammett substituent constants. From the results of statistical analysis the effect of substituents on CO, ？ and ？ proton and carbons are explained.

INTRODUCTION

With microwave irradiation of substituted benzaldehydes and aromatic ketones in presence of anhydrous zinc chloride gave exclusively high yield of substituted styryl chalcones.1 Their basic skeletons of chalcones are widely figured in natural products and are known to have multi pronged activity.2 Many of the chalcones are used as agrochemical and drugs.3 Recently much attention has paid on the synthesis of chalcones mainly from acetophenone analogs4 with various aromatic benzaldehydes. Several catalysts5 such as basic alumina, Al2O3-AlPO4, P2O5-piperidone ultrasonic rays using C-200 and Lewis acids have been used for knovenogal condensation and bases or quaternary ammonium salts have also been employed. Further studies on the efficient synthesis of chalcones are of current interest because of their wide range of application. Thus the author to report here the first time a simple facile approach to synthesis high yield of substituted styryl 4-methoxy-1-naphthyl chalcones and investigate the substituent effects from infrared and nuclear magnetic resonance spectra were recorded.

 

EXPERIMENTAL SECTION

A mixture of substituted benzaldehydes (0.01mol) and 4-methoxy-1-naphthyl ketones (0.01 mol) and anhydrous zinc chloride (0.001mol) was taken in ACE tube and flushed with Argon and tightly capped. The mixture is subjected to microwave oven heating for 5-8 minutes in a domestic microwave oven (LG Microwave Oven MG-395WA) and then it is allowed to reach to room temperature. The reaction mixture was treated with ethanol and the separated solid was filtered, washed with n-Hexane and dried. The solid was recrystallised by benzene-hexane mixture6. The reaction is shown in Scheme 1. Compounds a-f and h are unknown and the remaining compounds are known.

Melting points were determined in open glass capillaries on Mettler FP51 melting point apparatus and are uncorrected. Infrared spectra (KBr, 4000-400 cm-1) were recorded on JASCO IR-700 Japan model spectrophotometer. The nuclear magnetic resonance spectra both 1H and 13C of chalcones were recorded using UNITYPLUS-300 “KIBSIPS” 300MHz spectrometer, operating at 200MHz frequency for recording 1H NMR spectra and 75.45 MHz frequency for recording 13C NMR Spectra. The micro analysis of the chalcones were performed in Perkin Elmer 240C Analyzer.

Scheme 1

Based on Hays and Timmons7 infrared carbonyl stretching frequencies of s-cis and s-trans conformers are assigned. The NMR chemical shifts (ppm) of ethylene α, β protons and carbons are assigned based on reported in earlier literature8. The Physical constants, micro analysis and spectral data of all chalcones are summarized in Table 1.

Substituent effects

Correlation study involves the prediction of ground state molecular equilibrations11 of organic substrates such as s-cis and s-trans isomers of alkenes, alkynes, benzoylchlorides, styrenes and α, β-unsaturated ketones from spectral data. Their use in structure parameter correlations has now becomes popular for studying transition state study of reaction mechanisms,12 biological activities and normal coordinate analysis.13 Dhami and Stothers14 have extensively studied the 1H NMR spectra of a large number of acetophenones and styrenes with a view to establish the validity of the additivity of substituent effects in aromatic shieldings, first observed by Lauterber.15 Savin and coworkers16 obtained the NMR spectra of unsaturated ketones of the type RC6H4-CH=CH-COCMe3 and sought Hammett correlations for the ethylenic protons. Solcaniova and coworkers17 have measured 1H and 13C NMR spectra of substituted phenyl styrenes and substituted styryl phenyls and obtained good Hammett correlations for the olefinic protons and carbons. Now a day’s scientists18 have paid more interest to correlate the group frequencies of spectral data with Hammett substituent constants to explain the substituent effect of organic compounds. Recently Dae Dong Sung and Ananthakrishna Nadar19 investigate elaborately the single and multi substituent effects by spectral data of biphenyl and 9H-Fluorenyl chalcones. With in the above view there is no information available in the literature in the past with substituted styryl 4-methoxy-1-naphthyl ketones. Hence the authors have synthesized thirteen chalcones of the above type using microwave irradiation technique. And the substituent effects of above compounds are investigated from infrared and NMR spectra were made.

Substituent Effects from infrared spectra

The carbonyl stretching frequencies (cm-1) of s-cis and s-trans isomers of present study are shown in Table 1 and the corresponding conformers are shown in (I).

The infrared spectra were all recorded on the KBr disc in order to avoid the shoulder formation20 on carbonyl doublets. The s-cis conformers exhibit higher frequencies than the s-trans conformers due to the bulkier naphthalene group causes greater strain and they enhance the higher absorption of carbonyl group of s-cis isomer than the s-trans isomer. These frequencies are separately analyzed through various Hammett sigma constants.

From the statistical analysis, there is no significant correlation obtained with Hammett sigma constants in s-cis conformers. This is the conjugation between the C=O and the -CH=CH- parts is less important due to non-co planarity arising out of non bonded repulsion between naphthalene and styryl parts in the systems. In s-cis conformers there issignificant correlation is obtained (r=0.995) with σR constants. Further no significant correlations are obtained for both conformers with σ+, σI and σR parameters except s-trans with σR constants. This is due to the cross conjugation of methoxy substituent in fourth position of naphthyl ring as shown in (II)

In view of the inability of some σ constants to produce individually satisfactory correlations, it was thought worthwhile to seek multiple correlations involving either σI and σR constants or Swain-Lupton’s F and R parameters. The correlation equations (1,2) generated are

Fig. 1Plot of νC=O (s-trans) of substituted styryl 4-methoxy-1-naphthyl ketones versus σR.

Some cases where both the group parameters were fail to predict collectively the substituent effects. This may treated exceptional and by large it is to be realized that the collective participation of either σI and σR parameters or F and R parameters is more dependent than that of any single parameters role to predict the substituent effects. A good single parameter correlation is shown in Fig. 1.

Substituent effects from NMR Spectra

1H NMR Spectra

The 1H NMR spectral signals of ethylenic protons in all chalcones investigated are assigned. The chemical shifts of Hα protons are at higher field than those of Hβ protons in all chalcones. The ethylenic proton signals give an AB pattern and the β protons doublet in most cases is well separated from the signals of the aromatic protons. The chemical shifts of α, β protons are given in Table 1. The observation that Hα protons appear at higher field than that of Hβ protons makes the subject very interesting. This may possibly due to the polarization of C=C double bond in the system being predominantly caused by the carbonyl group so as to make electron density greater at the α position than that of β position.

Table 1Physical constants, micro analysis and spectral data of substituted styryl 4-methoxy-1-naphthyl ketones.

Table 2Results of statistical analysis of chemical shifts of H-α and H-β protons of substituted styryl 4-methoxy-1-naphthyl ketones

Table 3Results of statistical analysis of chemical shifts of H-α and H-β protons of substituted styryl 4-methoxy-1-naphthyl ketones with σI and σR or F and R parameters

The results of statistical analysis are presented in Table 2. All the attempted correlations involving substituent parameters gave only positive ρ values. This shows normal substituent effects is operates in all the chalcones. The Chemical shifts observed for Hα and the Hβ protons in the present investigation are correlated satisfactorily with Hammett sigma constants. In some cases correlation of Hβ with σ values is slightly better. By and large the necessity of enhanced σ values for correlation is not demanded by substituents. That the correlation with σI and σR parameters is not satisfactory in Hα implies that such σ values are incapable of predicting chemical shifts individually due to the domination of cross conjugation between carbonyl group and methoxy group in naphthyl ring. In Table 3 the multiple correlations involving either σI and σR or F and R values for these ketones are presented. It is indeed satisfactorily that in most cases the multiple correlations are successful. Some of the single parameter correlations are shown in Fig. 2, 3.

Fig. 2Plot of δH-α (ppm) of substituted styryl 4-methoxy-1-naphthyl ketones versus σ.

Fig. 3Plot of δH-β (ppm) of substituted styryl 4-methoxy-1-naphthyl ketones versus σ+.

13C NMR Spectra

From 13C NMR spectra the observed 13C Chemical shifts of Cα and the Cβ carbons are presented in Table 1. These chemical shifts are correlated with various Hammett substituent constants. The results of statistical analysis of substituent effects on Cα and Cβ carbons are shown in Table 4. There is a fair degree of correlation obtained for Cα and the Cβ carbon chemical shifts with Hammett sigma constants. The degree of transmission of electronic effects is found to be higher with Cα carbon than Cβ carbon. Uniformly σI and σR parameters or F and R values are adequately explain the substituent effects in all chalcones are evidenced from the correlation equations which are given in Table 5.

Table 4Results of statistical analysis of chemical shifts of C-α and C-β protons of substituted styryl 4-methoxy-1-naphthyl ketones

Table 5Results of statistical analysis of chemical shifts of C-α and C-β carbons of substituted styryl 4-methoxy-1-naphthyl ketones with σI and σR or F and R parameters

Fig. 4Plot of δC-α (ppm) of substituted styryl 4-methoxy-1-naphthyl ketones versus σ.

In single parameter correlations, there are satisfactory correlations obtained with σ+ values for Cα and Cβ carbons. This implies that one need not attach any significance to the correlations involving σ values. A good single parameter correlation is shown in Fig. 4.