SYNTHESIS OF CINNAMIC ACID BASED ON PERKIN REACTION USING SONOCHEMICAL METHOD AND ITS POTENTIAL AS PHOTOPROTECTIVE AGENT

Cinnamic acid plays a vital role in the synthesis of other important compounds and as a precursor for the synthesis of commercial cinnamon esters used in perfumery, cosmetics, and pharmaceutical industries. The aim of this research is to synthesize cinnamic acid using sonochemical methods. Cinnamic acid was synthesized using Perkin reaction by reacting 0.05 mole of benzaldehyde with 0.073 mole of acetic acid anhydride and 0.03 mole of sodium acetate as a catalyst in the Erlenmeyer flask and then the mixture was put in a sonicator for 60 minutes at 70 oC. The synthesized compound was tested organoleptic properties, and the melting point was measured. The chemical structure was elucidated using FT-IR, H-NMR, and 13C-NMR. The photoprotective activity was examined from its antioxidant and SPF values. The synthesized compound was found in the form of a shiny white fine crystal which had distinctive odor with a yield of 4.98% and the melting point was found at 133 oC. In the structure elucidation using FT-IR (the aromatic ring absorption at the wave number 1580 cm-1 1600 cm-1. The wave number 1625 cm-1is an aromatic conjugated alkene group, while wave number 1689.4 cm-1 is a carbonyl group. The wave number 2500 cm-1 – 3250 cm-1 is an OH carboxylic acid group) , H-NMR (7.410 (m, 5H, Ar-H); 7.425(t, 1H); 7.572 (d, 1H); 8.057 (d, 1H,C=CH) and 13C-NMR (129.309 ppm; 130.998 ppm; 134.58 ppm; 170.017 ppm) showed that when compared with the standard compound as the reference, the synthesized compound was confirmed to be cinnamic acid. The antioxidant activity test showed that at the concentration of 20 ppm the synthesized compound was able to reduce free radicals by 46.69%. This finding showed that the synthesized compound had antioxidant activity.


INTRODUCTION
Cinnamic acid belongs to the group of aromatic carboxylic acids with a C6-C3 structure. This compound is naturally found in plants [2] The biochemical process produces lignin into plant cell walls [3] Cinnamic acid is formed in the biosynthetic pathway leading to phenylpropanoids, coumarins, lignin, isoflavonoids, flavonoids, stilbene, auron, anthocyanins, spermidine and tannin [4] Cinnamic acid is an organic acid which has low toxicity, has extensive biological activity, has several active compounds that can be derivatized to new compounds, and can be developed into new drug compounds. Many derivatives of cinnamic acid have health benefits as antioxidants and free radical scavengers. Derivatives of cinnamic acid also have anti-bacterial, antiviral, and anti-fungal properties [5] Cinnamic acid is easily obtained by Perkin synthesis using benzaldehyde in acetic acid anhydride in the presence of weak bases such as acetate salts from alkali metals [6][7]. Perkin reaction is the method most frequently used for the synthesis of cinnamic acid and its derivatives . But the main shortcoming of this method is the reactions of aldehydes in the basic environment results in side products. Moreover, this reaction requires a long time between 4-10 hours in high temperatures [6].
Sonochemistry is becoming increasingly important for various organic synthesis reactions, by utilizing ultrasonic waves as an energy source to produce radicals and start the process of electron transfer, to affect the rate of chemical reactions and the yield.
Various types of ultrasonic wave-assisted organic synthesis reactions have been reported such as synthesis of thiodiazole [8], N-alkilbenzimidaxole [9], and arylthioamide [10]. Sonochemistry has also been used for condensation reactions, such as synthesis of chalcones using Claisen condensation [11] and in Knoevenagel condensation for synthesizing coumarins [12]. Sonochemistry has also been successfully applied to reactions in aqueous media [13] Cinnamic acid and its derivatives show high antioxidant activity, due to the presence of vinyl groups in it. However, the antioxidant activity is strongly influenced by the presence of substituents in various positions in the aromatic core. [14].
Cinnamic acid can be used as a sunscreen.
Hammer, in 1891, created the first sunscreen in history, using benzyl salicylate class, a derivative of p-amino benzoic acid, cinnamic acid, and benzophenon [15]. Cinnamic acid and its derivatives are a class of active sunscreen substances. This group of compounds has chromophore groups which absorb ultraviolet radiation. The photoprotective activity of plant extracts and isolated compounds is evaluated through many reports and research, which shows that there is a correlation between photoprotective activity and antioxidant activity. This is something that is especially interesting for the cosmetics industries for its usage in sunscreens, such as the flavonoids and cinnamic acid derivatives. [15]. Based on these descriptions, this study seeks to develop a simple sonochemical approach to the synthesis of cinnamic acid and its potential as a photoprotectives.

Instrumentation
The equipments and instruments used in this study werere glasswares, analytical balance, plastic basin, sonicator, FT-IR spectrometer (Agilent technologies), H-NMR and C-NMR spectroscopes, melting point apparatus, sets of distillation apparatus, Buchner funnel, and silica TLC plates.

Materials
The materials used in this study were benzaldehyde (pa), acetic acid anhydride (pa), sodium acetate (pa), concentrated hydrochloric acid, ethanol, and sodium bicarbonate.

Cinnamic acid synthesis
The cinnamic acid synthesis used the procedure based on [7] with slight modifica-

Photoprotective activity test
The determination of photoprotective activity was done by determining the in vitro SPF value using spectrophotometric methods.
The synthesized compound is dissolved in ethanol with concentration from value was calculated based on the Mansur equation [18].
(2) SPF : Sun Protection Factor, EE : Erythema effect spektrum, Abs : Absorbance, CF : Correction factor (10). The value of EE x I is a constant that shows the value of wavelengths from 290 to 320 nm and in the scale of 5 nm [18].

RESULTS AND DISCUSSION
The synthesis of cinnamic acid in this study was based on the Perkin reaction between benzaldehyde and acetic acid anhydride using anhydrous sodium acetate as the catalyst [6][7]   The activation of the methyl group as nucleophilic is carried out by the addition of a basic catalyst [6].
The use of sonochemical methods in organic synthesis offers a shorter reaction time, higher yield [9], and it's more environmentally friendly because it minimizes waste and energy use [10]. Ultrasonic wave assisted synthesis of cinnamic acid required 60 minutes of contact time at 70°C. The compound obtained then was crystallized using cold water to form fine crystals. The synthesized compound obtained has a yield of 4.98%.The yield of 4.98% is greater than the amount of cinnamic acid obtained from cinnamon bark isolation, which is 2.20% yield [19]. Factors that influence the small yield produced was the use of anhydrous sodium acetate catalyst. Aldehydes in the presence of bases will produce undesirable side products [6]. From this study, the use of anhydrous sodium acetate as a catalyst can be concluded to be less effective. For future research, it is better to use another acetate salt catalyst, for example potassium acetate [1]. The results of the 1H-NMR and 13 C-NMR spectroscopy of the synthesized compound in methanol can be seen in Figure   4 and Figure 5.