Garlic Catalyzed and Grindstone Assisted Solvent Free Green Synthesis of Pharmaceutically important Schiff Bases

 

Pooja Bedi¹, Goutam Pramanik², Tanay Pramanik^{1, 3}*

¹Department of Chemistry, School of Chemical Engineering and Physical Science,

Faculty of Technology and Sciences, Lovely Professional University, Phagwara, P.O. Box 144411, India.

²Institute of Organic Chemistry and Biochemistry of the CAS, Flemingovonam. 2, 16610 Prague 6,

Czech Republic.

³Department of Chemistry, University of Engineering and Management, University Area, Action Area III, B/5, Newtown, Kolkata-700160

 

ABSTRACT:

Present research work demonstrates the use of garlic as natural biocatalyst for green synthesis of a series of Schiff bases which are an important class of pharmaceutically important compounds, employing p-toluidine and variety of aromatic aldehydes as reactants. The products were obtained with good percentage of yield by simply grinding the reactants together with pestle in a mortar in presence of a piece of garlic in a completely solvent free condition. The synthesized crude products were purified by recrystallization from hot ethanol to obtain pure Schiff bases which were characterized by melting point, FTIR, ¹H-NMR and ¹³C-NMR. Through this work, a very simple, eco-friendly, effective, economic and new methodology is developed for synthesis of Schiff bases.

 

1. INTRODUCTION:

Green chemistry which has large number of applications in synthetic organic chemistry is an emerging field of research in the discipline of chemical science. The application of Green Chemistry in organic synthesis not only dramatically decreases the chemical waste and reaction time but also provide us with pure products in excellent yield. Recently this green chemistry has been manifested in many organic synthesis and chemical transformations.

 

The aim of our present research work has also used green methodology for the synthesis of Schiff bases. It helps us to reduce the use of hazardous substances owing manufacturing of chemical products¹. This green synthetic technique involves an alternative reaction medium or catalyst to substitute non ecofriendly solvents or toxic catalysts those have been routinely used in the organic synthesis^2-4.

 

One of the most important bio active class of organic compounds containing carbon nitrogen double bond is Schiff bases and they are illustrated by the general formula: R₃R₂C = NR₁. They are basically condensation product of 1 degree amines with carbonyl compounds and these Schiff bases can serve as an excellent precursor for synthesis of a large number of macro heterocyclic compounds. They are very good ligands^5-12 for formation of various metal-ligand complex and they also serve as intermediate for the preparation of large number of organic and organometallic compounds. Schiff bases are important class of organic compounds which exhibit variety of biological properties such as antibacterial¹³, antiviral¹⁴, anti-tuberculosis¹⁵, anti-inflammatory¹⁶, anticancer¹⁷, antitumor¹⁸, anticonvulsant¹⁹, antimicrobial²⁰, anti-dyslipidemia²¹ and analgesic²² properties. They have also found their applications in photophysical processes, nonlinear optics, catalysis, material science and magnetic chemistry²³.

 

In literature, various techniques are reported for the synthesis of Schiff base^24-25. Numerous solvent free and metal catalyzed reactions were also reported^26-30 for synthesis of Schiff Bases. However those literatures reported methodologies have shortcomings in one way or other. They have made use of expensive, non-biodegradable catalysts or toxic, non-ecofriendly solvents.

 

Grindstone technique involves a type of physical force (i.e. frictional force) which produces the necessary heat energy for carrying out reaction. Use of grindstone techniques for organic synthesis is also reported in literature by many researchers^31-33. Garlic being completely biodegradable, nontoxic and mild acidic in nature (p^H 5.61) has great potentiality to be used as a green bio-catalyst for synthesis of Schiff bases because Schiff bases  are nothing but the simple product of acid catalyzed condensation reaction of aromatic amine and aromatic aldehyde.

 

Although recently our research team has contributed significantly towards development of green methodology for multi component condensation reactions^34-38, to the best of our knowledge, no attempt has been taken by any researcher till date to synthesize Schiff base via grindstone techniques using garlic or any such material as natural biocatalyst. Thus we felt an urgent need to develop a simple, easy, new and green methodology for grindstone assisted green synthesis of a series of Schiff base in a completely solvent free condition employing garlic as natural and ecofriendly biocatalyst for the very first time ever.

 

2. EXPERIMENTAL SECTION:

2.1. General:

All the commercially available reactants and chemicals were used straightway as they were obtained from the suppliers, without doing any further purification. Garlic (scientific name Allium sativum) which is a species in the onion genus and commonly available in central Asia was bought directly from market. Their peels were taken off carefully and after washing them thoroughly with water the garlic was crushed to obtain the garlic juice. The pH of the garlic juice was found to be 5.61 as checked with the help of handy pH meter.

 

The synthesized compounds were characterized by melting point, IR, ¹H and ¹³C NMR spectroscopy. All the NMR spectra were recorded with Bruker ACF300 or DPX 300 or DPX 500 spectrometer in CDCl₃ solvent.

 

As the synthesized molecules are not entirely new molecules rather they are the molecules which are already reported in literature, the synthesized molecules are characterized by meting point, IR, ¹H and ¹³C NMR spectroscopy and the obtained results are verified by comparing the same with literature reported characterizations. The melting point, IR and NMR spectra of the prepared compounds were identical to those of reported ones.

 

For implementation of grindstone technique efficiently, the usages of liquid aromatic aldehydes as reactants were completely avoided and only the solid aromatic aldehydes were chosen to be used as starting materials.

 

2.2. General procedure for garlic catalyzed synthesis of SBs via grindstone technique:

A mixture of p-toluidine (2.5mmol), substituted benzaldehyde (2.5mmol) and a piece of garlic were grinded together in a mortar with a pestle in a completely solvent free condition for specific time duration. The mixture turns pasty after few minutes of grinding. The progress of the reaction was successively monitored by checking TLC. The solid crude product obtained at the end of the reaction, was recrystallized from absolute ethyl alcohol to get pure SBs as white/yellowish solid. The characterizations of obtained SBs were done by melting point, IR and NMR. The melting point, IR and NMR spectra of the obtained compounds were identical to those of reported ones.

 

2.3 Characterization:

1. 4-methyl-N-[(4-chlorophenyl) methylidene] aniline: (Entry-3a)

 M. P. 120-122°C,

 IR (KBr): 3087cm^-1 (C-H), 1621cm^-1 (C=N), 680.89 cm^-1 (C-Cl)

¹H-NMR (CDCl₃): 2.36 (s, 3H, -CH₃), 7.13 (d, 2H, Ar-H), 7.20 (d, 2H, Ar-H), 7.41(d, 2H, Ar-H), 7.83(d, 2H, Ar-H), 8.42(s, 1H, =CH)

¹³C-NMR (CDCl₃): 21.13 (C of CH₃), 120.9 (2C of Ar-C), 129.1 (2C of Ar-C), 129.94 (2C of Ar-C), 131.01 (2C of Ar-C), 134.91 (1C of Ar-C), 136.24 (1C of Ar-C-Cl), 137.23 (1C of Ar-C-CH₃), 149.11 (1C of Ar-C-N), 158.08 (1C of N=CH)

 

 

 

2. 4-methyl-N-[(4-bromophenyl) methylidene] aniline: (Entry-3b)

M. P. 136-138°C,

IR (KBr): 3084cm^-1 (C-H), 1671cm^-1 (C=N), 657.75 cm^-1 (C-Br):

¹H-NMR (CDCl₃): 2.36 (s, 3H, -CH₃), 7.12 (d, 2H, Ar-H), 7.18 (d, 2H, Ar-H), 7.60(d, 2H, Ar-H), 7.76(d, 2H, Ar-H), 8.4(s, 1H, =CH)

¹³C-NMR (CDCl₃): 21.15 (1C of CH₃), 120.9 (2C of Ar-C), 125.7 (1C of Ar-C-Br), 129.9 (2C of Ar-C), 130.15 (2C of Ar-C), 131.08 (2C of Ar-C), 135.3 (1C of Ar-C), 136.27 (1C of Ar-C-CH₃), 149.09 (1C of Ar-C-N), 158.15 (1C of N=CH)

 

3. 4-methyl-N-[(4-nitrophenyl) methylidene] aniline: (Entry-3c)

M. P. 120-122°C,

IR (KBr): 3078cm^-1 (C-H), 1594cm^-1 (C=N), 1516 and 1338 cm^-1 (NO₂)

¹H-NMR (CDCl₃): 2.37 (s, 6H, -CH₃), 7.6 (t, 2H, -Ar-H), 7.72 (t, 2H, Ar-H), 8.04 (d, 2H, Ar-H), 8.3 (d, 2H, Ar-H), 8.93 (s, 2H, =CH) 

¹³C-NMR (CDCl₃): 21.168 (1C of CH₃), 121.29 (2C of Ar-C), 124.59 (2C of Ar-C), 129.767 (2C of Ar-C), 131.08 (2C of Ar-C), 133.61 (1C of Ar-C-CH₃), 137.09 (1C of Ar-C-CH=), 148.5 (1C of Ar-C-N), 149.3 (1C of Ar-C-NO₂), 154.89 (1C of N=CH).

 

 

4. 4-methyl-N-[(3-nitrophenyl) methylidene] aniline: (Entry-3d)

M. P. 84-86°C,

IR (KBr): 3096cm^-1 (C-H), 1623cm^-1 (C=N), 1528 and 1347cm^-1 (NO₂)

¹H-NMR (CDCl₃): 2.37 (s, 3H, -CH₃), 7.22 (m, 4H, Ar-H), 7.63 (t, 1H, Ar-H), 8.23 (d, 1H, Ar-H), 8.30 (d, 1H, Ar-H), 8.53 (s, 1H, Ar-H), 8.71 (s, 1H, =CH)

¹³C-NMR(CDCl₃): 21.17 (1C of CH₃), 121.03 (2C of Ar-C), 123.48 (1C of Ar-C), 125.47 (1C of Ar-C-CH=N), 129.8 (1C of Ar-C), 130.03 (2C of Ar-C), 134.07 (1C of Ar-C), 137.06 (1C of Ar-C-CH₃), 138.10 (1C of Ar-C-CH=N), 148.28 (1C of Ar-C-NO₂), 148.75 (1C of Ar-C-N=),156.33 (1C of N=CH)

 

5. 4-methyl-N-[(2-nitrophenyl) methylidene] aniline: (Entry-3e)

M. P. 70-72°C,

IR (KBr): 3077cm^-1 (C-H), 1609cm^-1 (C=N), 1512 and 1335cm^-1 (NO₂)

¹H-NMR (CDCl₃): 2.38 (s, 3H, -CH₃), 7.2 (m, 4H, Ar-H), 8.06 (d, 2H, Ar-H), 8.3 (d, 2H, Ar-H), 8.55 (s, 1H, =CH)

¹³C-NMR(CDCl₃): 21.2 (1C of CH₃), 121.1 (2C of Ar-C), 124.08 (1C of Ar-C), 129.3 (1C of Ar-C-CH=N), 129.83 (1C of Ar-C), 130.53 (2C of Ar-C), 130.08 (1C of Ar-C), 137.34 (1C of Ar-C), 141.85 (1C of Ar-C-CH₃), 148.32 (1C of Ar-C-NO₂),  149.2 (1C of Ar-C-N=)156.43 (1C of N=CH)

 

Scheme 1: Synthesis of SBs by using garlic as natural acid biocatalyst via grindstone technique.

 

Figure 1: Structure of various derivative of synthesized SBs.

 

 

3. RESULTS AND DISCUSSION:

It is observed that formation of Schiff base takes place by condensation between carbonyl compounds and primary amines. The reaction is facile owing to the good electrophilic nature of carbonyl compounds and nucleophilic nature of amines.

 

All the products were obtained successfully simply by grinding a qui-molar mixture of aromatic aldehyde and aromatic amine with the help of mortar and pestle. All the reactions were carried out in completely solvent free condition, employing garlic as a green catalyst (As shown in scheme-1).

 

Table1: Grindstone assisted, garlic catalyzed synthesis of SBs with different aldehydes

 

The obtained results are summarized in table-1.  From table-1 it is clear that the reactions have taken 5-12 minutes time duration for completion. 

 

The reactions have exhibited significant dependence on the electronic nature of aromatic aldehyde. Inductive effect of ‘X’ and its vicinity to carbonyl group greatly influence the product yield as well as the reaction time.

 

It is worthy to note that the reactions with electron deficient aromatic aldehydes produce more percentage of yield and the percentage yield of the products decreases with decrease in electron withdrawing effect of the functional group X. So the reaction with 4- NO₂benzaldehyde gives maximum percentage of yield whereas the reaction with 4-Br benzaldehyde gives comparatively lower percentage of yield.

 

The reaction time also varies depending on the electron withdrawing effect of X. Thus the reaction takes minimum time with 4- NO₂-benzaldehyde and maximum time with 4-Br-benzaldehyde.

 

4. CONCLUSION:

In this work, we have demonstrated a very simple, easy, efficient, cost effective, ecofriendly and new methodology for grindstone assisted synthesis of Schiff base, using garlic as natural biocatalyst in a completely solvent free condition. This method has a number of benefits like simple experimental set up, relatively short duration of reaction, low cost and at last but not the least it is in accordance with the protocols of green chemistry. This is the first of its kind study where garlic is successfully explored as green bio catalyst for solvent free green synthesis of Schiff base for the very first time ever in literature. This work will motivate the researcher to use garlic/ other such bio catalysts instead of toxic catalyst/ solvents for ecofriendly synthesis of Schiff bases or other such organic molecules of biological importance.

 

5. CONFLICT OF INTEREST:

Declared none.

 

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Received on 16.06.2019           Modified on 10.07.2019

Accepted on 10.08.2019         © RJPT All right reserved