Substituent effects of 2-aryl-trans-decahydroquinolin-4-ones in CTADC oxidation : Spectrophotometric approach

A kinetic study was carried out using spectrophotometric approach on the oxidation of nine differently substituted 2-aryl-trans-decahydroquinolin-4-ones by Cetyltrimethylammonium dichromate (CTADC) as oxidant at 30°C and in aqueous acetic acid (50%) containing catalytic amount of sulphuric acid (6N). The reactions were studied at 350 nm. The reaction was found to follow second order kinetics. The substitution of methyl group at position three of the decahydroquinoline ring and the presence of electron releasing groups in the aryl group increased the rate of oxidation of the substrates. The change in the rate of oxidation with temperature and solvent composition was also studied. The products formed during the oxidation were also confirmed by using high-performance liquid chromatography (HPLC) and spectral analysis.


INTRODUCTION
The kinetic studies on the oxidation of different aliphatic (Singh et al., 1982;Mahadevappa and Swamy 1988;Singh et al., 1978a;Chiba et al., 1995), alicyclic (Mushran et al., 1976;singh et al., 1978b;Karnojitzky 1981), aromatic (Ogata and Sawaki 1972;Manivannan and Maruthamuthu 1986;Khandual et al., 1973;Annapoorna et al., 1998;Devries et al., 1995) ketones and a series of 2,6-diaryl-4-piperidones (Kumabe et al., 2001;Selvaraj et al., 1979) have been studied extensively by various workers and suitable mechanisms have been proposed.Recently the kinetics of oxidation of present ketones were reported in aqueous acetic acid using thallium(III), cerium(IV) and lead(IV) (Satyanarayana et al., 2010(Satyanarayana et al., , 2013a, b) , b) as oxidizing agents.In the present study CTADC was selected as oxidizing agent, as it is found to be selective, mild phase transferring and chemoselective oxidant (Patel andMishra, 2007a, 2004b;Sahu et al., 2005;Patel and Mishra, 2006c, d).It was found to *Corresponding author.E-mail: dr.b.haribabu@gmail.comAuthor(s)  oxidize aromatic amines and thiols to the corresponding coupled dehydrogenated products (Patel and Mishra, 2004b), aldoximes to the nitriles (Sahu et al., 2005), cholesterol to 7-dehydrocholesterol (Patel and Mishra, 2006c), arylthiourea to corresponding urea (Sahoo et al., 2010), alcohols to ketones (Vimala et al., 2009), oxidation of diols (Patel et al., 2008f) selectively.However, the study of the kinetics of oxidation of 2-aryl-transdecahydroquinolin-4-ones with CTADC was not reported so far.The present investigation was taken up with a view to identify whether the complex reagent CTADC useful for oxidation of the said ketones and also to identify the possible products during oxidation process.Hence, it is considered to investigate the kinetics of oxidation of 2-aryl-trans-decahydroquinolin-4-ones and also to study the effect of substituent(s) in aryl group and in the heterocyclic ring.This prompted the authors to carry out the investigation on a total nine compounds (1-9) (Figure 1).

Preparation of ketones
The ketones were prepared by the method developed by Baliah and Natarajan (1981), and purified by recrystallization from suitable solvents to constant melting points.All the samples were dried in vacuum before use.Cetyltrimethylammonium dichromate (CTADC) was prepared by the known method (Patel et al., 2005f) and its purity was checked by estimating Cr(VI) iodometrically (Vogel, 1961).

Acetic acid
Acetic acid glacial (Excelar), supplied by 'Qualigens Fine Chemicals', was refluxed with chromium trioxide for 6 h and fractionally distilled.The fraction boiling at 390-391K was collected and was used.

Other reagents
Cetyltrimethylammonium bromides, Potassium dichromate, Potassium iodide, Sulphuric acid used were all A.R grade.Doubly distilled water was used for all purposes.

Instrument
The instrument used was analytical technologies UV/visible spectrophotometer of Model Spectro2080.

Kinetic procedure
The oxidation kinetics of 2-aryl-trans-decahydroquinolin-4-ones by CTADC in the presence of aqueous acetic acid using a UV-Vis spectrophotometric method and all the kinetic measurements were carried out at 350 nm (Figure 2).The measurements were performed in 50:50(v/v) acetic acid: water containing 6N H 2 SO 4 at 30°C.The temperature was controlled by using thermostat of accuracy ±0.1°C.The required amount of CTADC solution was prepared by dissolving the necessary amount of CTADC in the solvent medium.The solutions of the substrates (ketones) were prepared by dissolving the appropriate quantity of the compounds in the same solvent, so that the concentration of the ketones was maintained always higher than the concentration of CTADC.The reaction was initiated by mixing CTADC to ketones and the progress of the reaction was followed spectrophotometrically by monitoring the decrease in absorbance at 350 nm.The second order conditions were followed for determining the rates of the reactions.

Product analysis
A mixture of ketone and CTADC was allowed to react in aqueous acetic acid (50%, v/v) in presence of sulphuric acid (6.0 N).The concentration of CTADC was maintained slightly excess than the concentration of ketone.The resulting mixture was kept aside at 30°C temperature for 2 to 3 days.The mixture turned reddish green, indicating the formation of reduced Cr (III).After that the reaction mixture was neutralized with saturated solution of sodium carbonate, extracted with ether and the combined ether extract separated and the crude product was obtained after distillation of the ether layer.

Stoichiometry
The stoichiometry of the reaction was determined by allowing a known excess of the oxidant CTADC to react with the substrate in solvent medium at 30°C and the un-reacted CTADC was estimated.The stoichiometry was found to be in the mole ratio of 1:1 for oxidant to substrate.R 2 C=O + CTADC Product + Cr(III)

Calculation of the rate constants
The rate constants were calculated using the second order rate equation: Where, a = Initial concentration of substrate in moles/lit; b = Initial concentration of CTADC in moles/lit.x = Amount of CTADC reacted in time t (seconds); t = Reaction time in seconds.

RESULTS AND DISCUSSION
A kinetic study was made on the oxidation of 2-aryl-transdecahydroquinolin-4-ones (1 to 9) by using CTADC as oxidizing agent in aqueous acetic acid (50%) medium.
The reaction was found to follow over all second order kinetics.The rate constants obtained for the selected substrates were given in Table 1.
An examination of the rate constants for the oxidation of 2-aryl-trans-decahydroquinolin-4-ones 1 to 3 (where there is no methyl group at 3 rd position) and those of corresponding 3-Methyl-2-aryl-trans-decahydroquinolin-4ones 5, 6 and 7 (where there is methyl group at 3 rd position) revealed that the latter series of compounds 5, 6, and 7 were oxidized at a faster rate than former series of compounds 1 to 3.This observation is as expected as the electron-releasing inductive effect of methyl group in heterocyclic ring enhances the rate of oxidation of these series of compounds.However, the observation made in the present investigation was found to be contrary to the observations made by us in earlier studies for same compounds with metal ions Tl(III), Pb(IV) and Ce(IV) (Satyanarayana et al., 2010(Satyanarayana et al., , 2013a(Satyanarayana et al., , 2013b)).The results of the study were given in Table 2.
The introduction of electron releasing and electron withdrawing substituent's on the phenyl group at orthoand para-positions had provided useful information to know the structure-activity relationship of these compounds.Substitution at ortho and para positions of aryl ring is expected to produce negligible effect on the rate of oxidation, because aryl ring is far away from the reaction centre.But the substituents at ortho and para positions played a vital role on rate of oxidation.This may be mainly due to the polar effect exerted by the substituents.The electron releasing groups increased the rate of oxidation.For example for compounds 1 to 3, the rate of oxidation  was found to be increased with increase in electron releasing nature of the substituent at p-position of phenyl ring.But, the trend was not followed for compound 7 that is, for p-methoxy substituted compounds in case of 3methyl substituted compounds 5 to 7.This may be because highly bulky methoxy substituent on phenyl ring in addition to 3-methyl substituent on decalin ring.The introduction of a methyl group in the 3 rd position in decalin ring increased the rate of oxidation of ketones, because of the combined effects of inductive as well as steric and was discussed above.But, further introduction of methyl group on 1 st position that is, on N atom of heterocyclic ring has showed some influence on the rate of oxidation.The rate of oxidation of 1, 3-dimethyl-2phenyl-trans-decahydroquinolin-4-one (9) (presence of methyl group at both 1 and 3 positions) was found to be high when compared with the rate of oxidation of compound (1), having no methyl group in position 3 but was showed less rate of oxidation compared to compound 5 (having methyl group at position 3).Further the rate of oxidation of 2-o-chlorophenyl-transdecahydroquinolin-4-one was expected to be low, but was found to be high when compared with the rates of oxidation of compounds 1 to 3 and is almost similar to the rate constant of compound 8.This type of higher rate constant of o-chloro compound was already reported in oxidation of the same compounds with thallium (III) and lead (IV) metal ions (Table 2) but has not gained proper reason.
The oxidation kinetics of 2-aryl-transdecahydroquinolin-4-ones has also been carried out in different compositions of acetic acid and the relevant data was given in Table 3.The concentration of sulphuric acid was maintained constant at 6.0 N in all these studies and the temperature was maintained at 30°C.Increase in the percentage of acetic acid of the medium increases the rate of oxidation.Further increase in concentration of sulphuric acid also increased the rate of oxidation of the said compounds and the data was given in Table 4.This observation was quite consistent with Cr(VI) reagents where the oxidation potential of this type of reagents increases with increase in concentration of acid in the reaction medium.The oxidation studies were also carried out at different temperatures (Table 5).In product analysis, the completion of the reaction was confirmed by comparison of Thin layer chromatography (TLC) of starting material with reaction mixture.A preliminary examination was carried out in order to identify the product.A spectral study was carried out to establish the compound present in the crude product in the workup of the reaction mixture.An examination of the IR spectrum (Figure 3) of the product mixture revealed that they are quite different from the spectrum of the original compounds taken.
A broad peak (3452 cm -1 ) in the region of 3300 to 3460 cm -1 indicated the presence of -OH of a carboxylic group or an -N-H group in the mixture.The sharp peaks at 2918 and 2850 cm -1 indicated the presence of aromatic system.Further, on spraying ninhydrin reagent on TLC of the product mixture gave spots of purple color.These spots might be due to presence of nitrogen atom in the crude product.
The earlier reports in respect of oxidation of the present type of systems indicated that the product is an amino acid (Meenal andRoopakalyani 1988a, Dhar andVardarajan 1991;Satyanarayana et al., 2010Satyanarayana et al., , 2013b)).However, the earlier authors have not conclusively confirmed the formation of amino acid.This prompted the present authors to isolate the product from the oxidation of compound (3) through reverse phase HPLC and was successfully isolated the products.The products were analyzed through 1 H NMR (Figure 4) and mass spectroscopy (Figure 5), which gave surprising results.
The 1 H NMR spectrum of this compound revealed that one of the products was p-methoxy benzamide and this was further confirmed by the mass spectrum of the product obtained (m/z=152.2).These observations prompted us to suggest that probably the carbon-nitrogen bond of alicyclic ring and piperidone ring might have been broken to form an amide, when the alicyclic ring was found to be completely broken from the heterocyclic ring.The other product is likely to be cyclohexane derivative which could not be identified and it needs further investigation.A reasonable scheme for the formation of the product is given in Scheme 1.

Conclusions
A kinetic study was carried out for the substituted 2-aryl-  compounds with CTADC.The products obtained during the oxidation were established.

Table 5 .
Effect of temperature on the oxidation of 2-Phenyl-4-one by CTADC.

Figure 3 .
Figure 3. IR spectrum of the crude product of compound 3.

Figure 4 .
Figure 4. 1 H NMR spectrum of the product of compound 3.

Figure 5 .
Figure 5. Mass spectrum of the product of compound 3.
agree that this article remain permanently open access under the terms of the Creative Commons Attribution License 4.0 International License Figure 1.2-aryl-trans-decahydroquinolin-4-ones.

Table 3 .
Effect of solvent composition on the oxidation of 2-Phenyl-4-one by CTADC.

Table 4 .
Effect of acid concentration on the oxidation of 2-Phenyl-4-one by CTADC.