L-Tyrosine as an Eco-Friendly and Efficient Catalyst for Knoevenagel Condensation of Arylaldehydes withMeldrum ’ s Acid in Solvent-Free Condition under GrindstoneMethod

We investigate L-Tyrosine as an efficient catalyst for the Knoevenagel condensation of arylaldehydes with meldrum’s acid containing cyclic active methylene group in solvent-free condition under grindstone method at room temperature to produce substituted-5-benzylidene-2,2-dimethyl-[1,3]dioxane-4,6-diones 3(a–j).


Introduction
Toda introduced a method called the grindstone method [1,2].In this method, solids are grounded together using a pestle and mortar to get the products.These reactions are more efficient selective than those carried out in the corresponding solutions.
Developing green chemical methods is one of the most important purposes of organic synthesis.Organic synthesis in the absence of solvent is a powerful tool for the generation of structurally different molecules whose special selectivity arises great interest.Moreover, solvent-free reactions are faster, taking just a few minutes.This aspect is coupled with the lowering of the total costs of running a reaction without solvent and specially designed equipment, which could become a very impressive factor in industry.
Tyrosine is known to be an efficient, bifunctional, zwitterionic, and ecofriendly catalyst.It is available in both the enantiomeric, (S)-Tyrosine and (R)-Tyrosine, forms.The two functional groups of tyrosine enable it to act both as an acid as well as a base catalyst in chemical condensation reactions.
In this paper, we highlight our findings on the L-tyrosine catalyzed condensation of arylaldehydes with meldrum's acid containing cyclic active methylene group in solvent-free condition under grindstone method at room temperature to produce substituted -5-benzylidene-2,2-dimethyl- [1,3]dioxane-4,6-diones in solvent-free condition under grindstone method at room temperature.

3(a-j) 1(a-j)
Scheme 1: Knoevenagel condensation of arylaldehydes with meldrum's acid in the presence of L-tyrosine in solvent-free condition under grindstone method.
In the absence of L-tyrosine, the reaction does not proceed the reactants in the solvent-free condition under grindstone method at room temperature for 4 h.The use of L-tyrosine as a catalyst helps to avoid the use of environmentally unfavourable organic solvents as reaction medium.
The above reactions of 1(a-j) with meldrum's acid were attempted in the presence of various amino acids like valine, glycine, alanine, and Lysine in the solvent-free condition under grindstone method at room temperature for 5 h.but there was not much progress in the reactions as seen by TLC examination of crude reaction mixtures.In the presence of phenyl alanine and L-tryptophan in the solvent-free condition under grindstone method at room temperature, there was a little bit of progress, but the reaction was not completed for 5 hrs.
The above reactions of arylaldehydes 1(a-j) with meldrum's acid containing cyclic active methylene group were attempted in the presence of L-proline low yield which was obtained for 1 h in the solvent-free condition under the grindstone method at room temperature.
The above reactions of arylaldehydes 1(a-j) with meldrum's acid containing cyclic active methylene group were attempted in the presence of various bases like NaOH, KOH which were too strong bases to result in more byproducts.Low yield was obtained and 3 h reaction time is needed using K 2 CO 3 , ammonium acetate, piperidine, and triethylamine as catalyst for condensation of arylaldehydes 1(a-j) with meldrum's acids containing cyclic active methylene group (2) in the solvent-free condition under the grindstone method at room temperature.
From Table 1, it was shown that the condensation of arylaldehydes with electron withdrawing group such as -NO 2 and -Cl at paraposition with meldrum's acid containing cyclic active methylene compounds can be carried out in relatively shorter time and higher yield than with electron donating group such as -OH, -OCH 3 , and N, N-dimethyl arylaldehydes in the solvent-free condition under the grindstone method at room temperature.
A plausible mechanism for the formation of 3 from 1 and 2 in the presence of L-tyrosine as catalyst is shown in Scheme 2. The reaction mechanism is supported by the literature reference [37].
In the mechanism shown in Scheme 2, L-tyrosine, in its zwitterionic form (Xb), abstracts a proton from meldrum's acid containing cyclic active methylene group (2) forming the carbanion of meldrum's acid (2 I ) which then attacks the protonated arylaldehydes (1 I ) forming the corresponding intermediate (1 II ) that loses water to form the end product 3.In summary, L-Tyrosine as an efficient catalyst for the preparation of substituted-5-benzylidene-2,2-dimethyl- [1,3]dioxane-4,6-dione by Knoevenagel condensation in the solvent free condition under the grind stone method at room temperature.This method is applicable to a wide range of arylaldehydes 1(a-j) and meldrum's acid (2) containing active methylene group to produce substituted -5benzylidene-2,2-dimethyl- [1,3]dioxane-4,6-diones 3(a-j) in solvent-free condition under grindstone method at room temperature.
The attractive features of this procedure are the mild reaction conditions, high conversions, operational simplicity, and inexpensive and ready availability of the catalyst, all of which make it a useful and attractive strategy for the preparation of substituted -5-benzylidene-2,2-dimethyl- [1,3]dioxane-4,6-dione in solvent-free condition under grindstone method at room temperature.

Experimental Section
Melting points were measured in open capillary tubes and are uncorrected.TLC was done on plates coated with silica gel-G and spotting was done using iodine or UV lamp.IRspectra were recorded using FT-IR in KBr phase. 1 H-NMR spectra were recorded at 400 MHz, respectively.Compounds are known, and products were identified by spectral and melting-point comparison with the authentic samples.
General Procedure for the Preparation of 3(a-j) from 1(a-j) and Meldrum's Acid.A mixture of 1 (10 mmol), meldrum's acid 2 (10 mmol), and L-tyrosine (2 mmol) was physically grinded in solvent-free condition under grindstone method at room temperature for a specified period of time (Table 1).After completion of reaction (as shown by TLC checking), the mixture was poured into ice-cold water (50 mL).The separated solid was filtered, washed with water (100 mL), and dried to obtain crude 3(a-j).The latter were then recrystallised from ethanol to afford pure 3(a-j).Compounds are known, and products were identified by spectral and melting-point comparison with the authentic samples.

2 Scheme 2 :
Scheme 2: Plausible mechanism for the formation of 3 from 1 and 2 in the presence of L-tyrosine under solvent-free condition at room temperature.