# Green Chemistry Influences in Organic Synthesis: a Review

Yehezkiel Steven Kurniawan, Krisfian Tata Aneka Priyangga, Philip Anggo

Krisbiantoro, Arif Cahyo Imawan

► To cite this version:

Yehezkiel Steven Kurniawan, Krisfian Tata Aneka Priyangga, Philip Anggo Krisbiantoro, Arif Cahyo Imawan. Green Chemistry Influences in Organic Synthesis: a Review. Journal of Multidisciplinary Applied Natural Science, 2020, 1, pp.1 - 12. 10.47352/jmans.v1i1.2. hal-04177672

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# Green Chemistry Influences in Organic Synthesis : A Review

Yehezkiel Steven Kurniawan*, Krisfian Tata Aneka Priyangga, Philip Anggo Krisbiantoro, and Arif Cahyo Imawan

Received : August 15, 2020

Revised : September 25, 2020

Accepted : October 8, 2020

Online : October 16, 2020

## Abstract

Environmental pollution and global warming cause serious problems in our life. Since the demand for human daily appliances had been increased by years, the organic chemical-based industries response that demand increment by increasing their production process. Because of that, the environmental pollution becomes worse and worse. Green chemistry thus was introduced to influence the chemical industries to strive for better environmental sustainability. Over 20 years, green chemistry principles have to influence the organic chemistry field especially as many researchers have put their attention on that field of research. So far, synthesis process involving organic compounds has been considered on waste prevention, safer solvents, design for high energy efficiency, and usage of renewable feedstocks. This review comprehensively discusses in brief about the implementation of green chemistry principles and their applications in the synthesis process of organic compounds.

**Keywords:** environmental sustainability, green chemistry, organic compound, synthesis process

## 1. INTRODUCTION

The recent environmental quality is depleting to an anxious level and greatly influences the human life [1]. Environmental pollution is defined as a serious environment status where the concentration of pollutant is higher than the normal level due to natural or artificial contamination. Shortly, environmental pollution is a disequilibrium condition in any system of environmental life [2]. Environmental pollution, including soil, water and air pollution, is worsened by days mainly due to industrial activities. Moreover, released greenhouse gasses deteriorate the environmental status by increasing the earth temperature (known as global warming). Those problems require serious attention to keep our sustainable environment. Therefore, industrial processes should not focus only on economic advantage and neglecting environmental protection [3].

In the ancient era, chemical industries mostly considered on the yield of reaction and the

purity of the desired product [4] and rarely consider about the environmental issues, energy usage, and the efficiency of the chemical process. Even though the national and international regulations have been decided for chemical industries, environmental pollution looks like a never-ending problem, especially in developing countries [5]. Because of that, since the governmental point of view seems not efficient enough to keep the environmental sustainability, researchers are doing their best to develop the chemical industries in a “green” and environmental-friendly stage [6].

Many efforts have been placed to develop and improve those environmental issues until Anastas and Warner introduced the green chemistry concept in 1998. Green chemistry is defined as the utilization of a set of principles that reduces or eliminates the usage or generation of hazardous substances in the design, manufacture and application of chemical products [7][8]. There are 12 principles of green chemistry as shown in Figure 1.

However, we mainly focused this review on 4 main principles, i.e. waste prevention, safer solvents, design for high energy efficiency, and usage of renewable feedstocks. However, the description of those four principles also briefly dilate the other principles. This review would also discuss on the implementation of green chemistry principle and their application in the

**Copyright Holder:**

© Kurniawan, Y. S., Priyangga, K. T. A., Krisbiantoro P. A., and Imawan, A. C. (2021)

**First Publication Right:**

Journal of Multidisciplinary Applied Natural Science

**This Article is Licensed Under:**

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synthesis process of organic compounds.

<figure><img src="image_5.png" /><figcaption>**Figure 1.** 12 Principles of green chemistry [8].</figcaption></figure>

## 2. WASTE PREVENTION

> "It always better to prevent the generation of waste rather than to manage or treat or eliminate them."

Waste is defined as byproduct material which is generated during a process. Waste from chemical processes always scary the human community because it is toxic, non-biodegradable, and radioactive. Furthermore, those wastes are continuously generated as long as the chemical industries are on operation [9]. In general, waste could be classified into 2 major classes, liquid and solid wastes. Liquid and solid wastes are distinguished by their phase either in liquid or solid form, respectively. Liquid waste usually contains acid, base, metal ions (precious metals, alkali and base metals and heavy metals), organic pollutants (dyes, biomolecules), and so on. Meanwhile, solid waste usually composed of plastics, paper, solid metals, ceramics, and glasses

[10].

The chemical process should be designed to incorporate all used materials as far as possible to form the desired product. Because of that, waste prevention should be manifested by rational and effective design of the chemical process using green chemistry quantitative metrics, such as effective mass yield, product efficiency, carbon efficiency, atom economy, reaction mass efficiency, ecoscale, environmental factor, and biologictool plots [11]. Effective mass yield is defined as the ratio between the mass of the desired product relative to the mass of all non-benign materials (water, dilute alcohol, NaCl, etc.) used in its chemical process [12]. However, this parameter is quite subjective to define "non-benign" material and it fails to describe the toxicity level of the chemical process. On the other hand, product efficiency is the ratio between the real mass of the desired product versus the theoretical total atomic mass of the desired product.

Carbon efficiency is a parameter which describes how much the carbon atoms are utilized in the product. Even though it is a good parameter for the pharmaceutical industry, this parameter is useless in inorganic industries such as the production of metal oxide, inorganic paint, inorganic polymer, and advanced materials. Barry Trost in 1995 designed the atom economy formula based on how much of the reactants present in the desired product. Although the atom economy calculation ignores the homogeneous catalyst and used solvents because they are not considered as reactants in the chemical process, atom economy still known as a good parameter for organic and inorganic processes as for today. However, it should be noted that atom economy is just a theoretical parameter since it is considered only from the handwriting reaction equation [13].

In contrast, reaction mass efficiency considers the atom economy, chemical yield and reaction stoichiometry. However, similar to carbon efficiency parameter, reaction mass efficiency is still an ideal calculation showing the "green-ness" of the reaction but not of the real process because it is neglecting any solvent and energy usage. In 2006, the ecoscale metric
was proposed by Van Aken et al. [14]. Similar to the effective mass yield parameter, the ecoscale gives a score from 0 to 100 considering account cost, safety, technical set-up, energy and purification aspects. It is obtained by assigning a value of 100 to an ideal reaction defined as "compound A undergoes a reaction with compound B to give the desired compound C in 100% yield at room temperature with a minimal risk for the operator and a minimal impact on the environment", and then subtracting penalty points for non-ideal conditions. However, this ideal condition is rarely established in the real chemical process.

So far, the environmental factor (E-factor) remains as one of the most flexible green chemistry quantitative metrics. Roger A. Shelton in 2007 [15] proposed the E-factor formula as the ratio between total waste over the desired product. E-factor considers the solvent and catalyst usage making it is comprehensive enough to evaluate the chemical process is environmentally friendly or not. The annual production of oil refining, bulk chemicals, fine chemicals and pharmaceutical processes are 106-108, 104-106, 102-104, and 10-103 tons, respectively. Meanwhile, the waste produced by oil refining, bulk chemicals, fine chemicals and pharmaceutical processes are 105-107, 104-105, 10-104, and 102-105 tons, respectively. These data show that the E-factor of oil refining, bulk chemicals, fine chemicals and pharmaceutical processes are 0.1, 1-5, 5-50, and 25-100, respectively. It means that the oil refining industry is the cleanest chemical industry while the pharmaceutical industry is the worst industry in the E-factor point of view as for today.

The latest green chemistry quantitative metrics called biologic tool plot was introduced by Lie et al. [16]. This parameter offers an easy representation of a chemical route from the available data such as starting material, intermediates and product names and chemical formula, and yields of reaction steps. The mass percentage of heteroatoms in the materials is plotted against their molar masses to obtain the biologic tool score. When the biologic tool score is closer to 1, the more rational the chemical route would be. This parameter is pivotal

to the design and evaluation of a whole chemical process in the industries. Equations for those green chemistry metrics are shown as below.

In our previous work, the esterification reaction of fatty acid with ethanol was developed to achieve a "greener" synthesis protocol for biodiesel production. The green quantitative metrics of that process are shown in Table 1. It was found that sulfuric acid gave a higher yield percentage and a higher reaction mass efficiency than KSF montmorillonite under reflux method. However, KSF montmorillonite gave 17 times lower E-factor than sulfuric acid process demonstrating that KSF montmorillonite-catalyzed reaction is better to be implemented as an alternative green method [17].

When waste prevention could not be avoided, waste remediation stage is absolutely required to minimize the negative effect on the environment [18]. Several liquid waste remediation techniques have been established, such as coagulation, precipitation, adsorption, bioremediation, and photocatalysis methods [9]. Coagulation and precipitation are carried out by changing the liquid state of the pollutants to solid or semi-solid state either by physical process (centrifugation) or chemical process (precipitated as their insoluble materials). Adsorption is a process by which solid materials are utilized to trap the pollutants on their pore and surface [18]. Bioremediation is a chemical process involving enzyme and/or microorganism for pollutant degradation [19]. While photocatalysis is defined as a chemical degradation process using a catalyst material under light irradiation [20]. On the other hand, solid waste treatment usually performed through an incineration process followed by landfill application [9].

As an example, phenol ($C_6H_5OH$) is a useful raw material on the production of herbicide, detergents, polycarbonate, bakelite, and nylon polymer materials. Although the demand for phenol is kept in-

$$ \text{Effective mass yield (\%)} = \frac{\text{mass of products} \times 100\%}{\text{mass of non-benign reagents}} \quad (1) $$

$$ \text{Product efficiency} = \frac{\text{real mass of the desired product} \times 100\%}{\text{theoretical total atomic mass of the desired product}} \quad (2) $$
$$ \text{Carbon efficiency (\%)} = \frac{\text{amount of carbon in product} \times 100\%}{\text{total carbon present in reactants}} \quad (3) $$

$$ \text{Atom economy} = \frac{\text{m.w. of desired product}}{\text{x 100\%}} \quad (4) $$

$$ \text{Reaction mass efficiency} = \frac{\text{molecular weight of the product}}{\text{x yield}} \quad (5) $$

$$ \text{E-factor} = \frac{\text{total waste}}{\text{product}} \quad (6) $$

creasing because of its irreplaceable role, phenol belongs as one of 129 dangerous pollutants according to the Agency for Environmental Protection [19]. Because of that, several phenolic wastewater treatments are developed and optimized. Phenol adsorption had been investigated using various heterogeneous materials to obtain as high as possible maximum adsorption capacity (mg phenol/g adsorbent). However, phenol desorption is sometimes not easy thus leaving a toxic solid material. Bioremediation of phenol becoming an alternative way to degrade phenol through enzymatic metabolism of bacteria, however, the bacteria require specific and stable environmental condition such as pH 7.4 at 310 K [21]. That limitation makes the chemical process is not facile enough to be carried out in a large-scale commercialization stage.

In contrast, phenol degradation to carbon dioxide and water is possible to be performed under light irradiation in the presence of metal oxide catalyst material [22]. This treatment is quite simple and efficient because it only needs light and reusable catalyst materials. In our previous work, we utilized red amaranth natural pigments to sensitize the P25 TiO₂ nanoparticles for phenol degradation under

visible light. Bare P25 TiO₂ did not give any photo-degradation activity under visible light, however, sensitized-P25 TiO₂ gave 22% photodegradation activity of phenol, which was remarkable [20]. This finding shows that a suitable combination of organic compounds with inorganic materials could serve as an ideal smart material for the phenol photodegradation to water and carbon dioxide.

### 3. SAFER SOLVENTS

> "Chemical products should be designed to optimize their function while minimizing their toxic effect."

Solvent is the major liquid compound which is required to dissolve the chemicals to form a solution. In a simple chemical process, sometimes a large volume of solvent is required for reaction media and/or purification stage [23]. Since the main role of the solvent is only for diluting the chemicals in the chemical reaction, it is quite possible to prevent the usage of flammable, toxic and environmentally damaging solvents such as benzene, carbon tetrachloride, formaldehyde, etc. [24]. Highly volatile solvents such as carbon tetrachloride are easily evaporated thus making hazardous air pollution as well as high risk for human exposure [23]. On the other hand, high polarity solvents such as formaldehyde are unfavorable because they are possible to be accumulated in aquatic environment generating health damages to human population [25]. Because of that, several efforts for solvent substitution are going on to achieve a better environmental sustainability. Of course, solvent-free reactions such as grinding method and sol-gel reaction are the most desirable condition on the chemical processes [26].

Benzene recently had been substituted by toluene due to its carcinogenic effect while carbon tetrachloride had been substituted by either chloroform or dichloromethane due to its effect in depleting the ozone layer of the atmosphere [27]. Byrne, et al. introduced "green solvent" term as an environmen-

<table><caption>**Table 1.** The green quantitative metrics esterification reaction of fatty acid under reflux using different catalyst [17].</caption><thead><tr><th rowspan="2">Parameter</th><th colspan="2">Catalyst</th></tr><tr><th>H<sub>2</sub>SO<sub>4</sub></th><th>KSF mont</th></tr></thead><tbody><tr><td>Yield (%)</td><td>90.0</td><td>52.0</td></tr><tr><td>Atom economy (%)</td><td>75.0</td><td>75.0</td></tr><tr><td>Reaction mass efficiency (mg/g)</td><td>11.0</td><td>6.3</td></tr><tr><td>E-factor</td><td>12.0</td><td>0.7</td></tr></tbody></table>

<figure><img src="image_6.png" /></figure>
<table><caption>**Table 2.** List of solvent recommendation according to Pfizer and Sanofi [28].</caption><thead><tr><th>Class</th><th>Solvent</th><th>Pfizer recommendation</th><th>Sanofi recommendation</th></tr></thead><tbody><tr><td rowspan="5">Alcohols</td><td>Methanol</td><td>Preferred</td><td>Recommended</td></tr><tr><td>Ethanol</td><td>Preferred</td><td>Recommended</td></tr><tr><td>1-Propanol</td><td>Preferred</td><td>Recommended</td></tr><tr><td>2-Propanol</td><td>Preferred</td><td>Recommended</td></tr><tr><td>1-Butanol</td><td>Preferred</td><td>Recommended</td></tr><tr><td rowspan="6">Hydrocarbons</td><td>Ethylene glycol</td><td>Usable</td><td>Substitution advisable</td></tr><tr><td>n-Pentane</td><td>Undesirable</td><td>Banned</td></tr><tr><td>n-Hexane</td><td>Undesirable</td><td>Substitution advisable</td></tr><tr><td>Cyclohexane</td><td>Usable</td><td>Substitution advisable</td></tr><tr><td>Benzene</td><td>Undesirable</td><td>Banned</td></tr><tr><td>Toluene</td><td>Usable</td><td>Substitution advisable</td></tr><tr><td rowspan="4">Dipolar aprotic</td><td>Xylene</td><td>Usable</td><td>Substitution advisable</td></tr><tr><td>Dimethyl sulfoxide</td><td>Usable</td><td>Substitution advisable</td></tr><tr><td>Acetonitrile</td><td>Usable</td><td>Recommended</td></tr><tr><td>N,N-dimethyl formamide</td><td>Undesirable</td><td>Substitution advisable</td></tr><tr><td rowspan="2">Esters</td><td>Methyl acetate</td><td>Preferred</td><td>Substitution advisable</td></tr><tr><td>Ethyl acetate</td><td>Preferred</td><td>Recommended</td></tr><tr><td rowspan="4">Ethers</td><td>Tetrahydrofurane</td><td>Usable</td><td>Substitution advisable</td></tr><tr><td>Diethyl ether</td><td>Undesirable</td><td>Banned</td></tr><tr><td>1,4-Dioxane</td><td>Undesirable</td><td>Substitution advisable</td></tr><tr><td>2-methyl tetrahydrofurane</td><td>Usable</td><td>Recommended</td></tr><tr><td rowspan="2">Ketones</td><td>Acetone</td><td>Preferred</td><td>Recommended</td></tr><tr><td>Methylethylketone</td><td>Preferred</td><td>Recommended</td></tr><tr><td rowspan="3">Halogenated</td><td>Carbon tetrachloride</td><td>Undesirable</td><td>Banned</td></tr><tr><td>Chloroform</td><td>Undesirable</td><td>Banned</td></tr><tr><td>Dichloromethane</td><td>Undesirable</td><td>Substitution advisable</td></tr><tr><td rowspan="3">Miscellaneous</td><td>Water</td><td>Preferred</td><td>Recommended</td></tr><tr><td>Acetic acid</td><td>Usable</td><td>Substitution advisable</td></tr><tr><td>Pyridine</td><td>Undesirable</td><td>Substitution advisable</td></tr></tbody></table>

<figure><img src="image_7.png" /></figure>
<table><caption>**Table 3.** List of the alternative solvents for a safer chemical process [28].</caption><thead><tr><th>Solvent</th><th>Issues</th><th>Alternatives</th></tr></thead><tbody><tr><td>n-Pentane</td><td>Low flashpoint</td><td>n-Heptane</td></tr><tr><td>Diethyl ether</td><td>Low flashpoint</td><td>2-Methyl tetrahydrofurane</td></tr><tr><td>Hexane</td><td>Toxic</td><td>Heptane</td></tr><tr><td>Benzene</td><td>Carcinogenic</td><td>Toluene</td></tr><tr><td>Chloroform</td><td>Carcinogenic</td><td>Dichloromethane</td></tr><tr><td>Pyridine</td><td>Carcinogenic</td><td>Triethylamine</td></tr><tr><td>N,N-dimethyl formamide</td><td>Reproductive toxicity</td><td>Acetonitrile</td></tr></tbody></table>

tally friendly solvent which is derived from the renewable sources with low net cumulative energy demand during its production process. As an example, ethanol is a “greener” solvent than N,N-dimethyl formamide because ethanol could be easily produced by a largescale fermentation process from the biomass waste. Table 2 lists the solvent classification according to Pfizer and Sanofi based on their environmental effect and the production energy intake [28].

In general, solvent-replacement is considered from the physicochemical properties of the solvent. As long as the alternative solvents have nearly same physicochemical properties to the used solvent, it is quite possible to do the solvent replacement. Those physicochemical properties are solubility (d), acidity (a), basicity (b) and polarity (p*) called as Kamlet-Taft parameters. Through a careful investigation of those parameters, a rational design on solvent replacement could be achieved [29]. Several alternatives solvents have been reported to minimize the environmental damages from the chemical processes and they are listed in Table 3. Supercritical fluids and ionic liquids are also recently welcomed in several chemical processes.

## 4. DESIGN FOR HIGH ENERGY EFFICIENCY

> "If possible, all chemical processes should be conducted at room temperature and pressure."

Chemical reactions sometimes need high temperature to pass the activation energy and/or make the reaction possible from the thermodynamic point of view. As examples, some inorganic materials require calcination at >700 K to form the desired crystal structure. On the other hand, organic reactions usually carried out through a reflux method [30]. Nowadays, several “green” reaction conditions have been established well such as sonochemistry, microwave chemistry, photocatalysis reaction and microfluidics reaction. The main keyword on applying the alternative reaction method is to deliver energy rapidly from the heat sources to the chemicals thus the reaction time could be drastically shortened. Another way to decrease the energy usage of the chemical processes is by using catalyst material to shorten the reaction and purification process [31]. Catalyst is a chemical substance that enhances the reaction rate by decreasing the activation energy, however, the catalyst itself does not undergo any permanent chemical change [32]. By

<table><caption>**Table 4.** The comparison of ethyl 9,10-dihydroxyoctadecanoate synthesis using reflux and sonochemistry methods [17].</caption><thead><tr><th rowspan="2">Parameter</th><th colspan="2">Method</th></tr><tr><th>Reflux</th><th>Sono-chemical</th></tr></thead><tbody><tr><td>Yield (%)</td><td>52</td><td>86</td></tr><tr><td>Atom economy (%)</td><td>75</td><td>75</td></tr><tr><td>Reaction mass efficiency (mg/g)</td><td>6.3</td><td>11</td></tr><tr><td>E-factor</td><td>0.7</td><td>0.4</td></tr><tr><td>Energy (kWatt)</td><td>15.998</td><td>257</td></tr></tbody></table>
changing the catalyst materials, it is possible to con-
trol the reaction selectivity as well as its stereo-
chemistry to obtain the desired product in very high
yield and purity percentage [33]. It means the selec-
tive and high catalytic efficiency of the catalyst ma-
terial is much better than obtaining racemic a mix-
ture in a time-consuming reaction.

Coming back to the green reaction conditions,
sonochemistry method is defined as a process utiliz-
ing the ultrasonic radiation (20 kHz – 10 MHz) to
undergo the chemical reaction. The main advantage

<figure><img src="image_8.png" /><figcaption>**Figure 2.** MAOS process for several organic reac-
tions.</figcaption></figure>

of the sonochemistry method is generation of the
hot spots with 5,000-25,000 K temperatures and
1,000 atm pressure at a very short time (heating rate
> 1011 K s⁻¹) due to unique cavitation phenomena
[34]. In our previous work, esterification of 9,10-
dihydroxyoctadecanoic acid with ethanol using
KSF montmorillonite as the catalyst with reflux and
sonochemical method had been investigated and the
results are shown in Table 4. It was found that
sonochemical method gave a higher yield and reac-
tion mass efficiency than reflux method. Further-
more, the E-factor and consumed energy were much
lower than reflux method demonstrating that sono-
chemical method is a better and greener way to pro-
duce ethyl 9,10-dihydroxyoctadecanoate [17].

Microwave-assisted reaction happens through a
suitable interaction between the chemicals and elec-
tromagnetic energy through collision and/or con-
duction process [35]. Recently, organic reaction
utilizing microwave heating is known as Micro-
wave-Assisted Organic Synthesis (MAOS) and it
had been thoroughly applied for some organic reac-
tions, such as ring-closing metathesis of diallyl de-
rivatives, intramolecular hetero-Diels-Alder cy-
cloaddition of alkenyl-tethered 2(1H)-pyrazolines,
cyclotrimerization reaction between the diyne and
benzonitrile, and so on [36]. For the cyclotrimeriza-
tion reaction, the reaction yield was significantly
improved from 9% (conventional heating) to 92%
using microwave-solid support method (300 Watt,

<figure><img src="image_9.png" /><figcaption>**Figure 3.** Photochemistry reaction for the produc-
tion of organic compounds.</figcaption></figure>

10 min), which was remarkable. The reaction
scheme of these compounds using microwave was
shown in Figure 2.

On the other hand, catalyzed photochemical reac-
tions such as Claisen rearrangement, Diels Alder
reaction, and other pericyclic reactions are greatly
focused due to manipulation of the orbital mole-
cules and/or charge transfer of the chemicals under
ultraviolet (400-750 nm) or infrared (750-2,500 nm)
irradiation [37]. The first photochemical reaction
was reported by Trommsdorff in 1834 by reacting a
-santonin under visible light. Through visible light
irradiation, the a-santonin was rearranged, dimer-
ized and reacted to form a single crystal [38]. Other
useful reactions are the transformation of (Z)-1,2-
diphenylethene to phenanthrene through a photoox-
idation reaction, and the transformation of benzene
to fulvene and benzvalene. Transformation benzene
to fulvene is remarkable because that finding breaks
an impossible issue of benzene to be degraded in a
very simple way [39]. The reaction scheme of these
compounds using photochemistry method is shown
in Figure 3.

Last but not least is the microfluidics reaction
which is defined as the reaction on the micro-vessel
device. Microfluidics offers high mass transfer rate
as well as large surface contact area and very short
diffusion distance [40][41]. Because of that, micro-
fluidics knowledge has been applied for several
applications including chemical synthesis. Yoshida
and coworkers have studied the application of the
microfluidic device to synthesis organic compounds
in submillisecond reaction time [41]. A very short
reaction time could be achieved due to extremely
fast reaction mixing which is impossible to be
achieved in conventional reactors. Additionally,
microfluidics offered higher reaction selectivity due
to good kinetic control thus suppressing the unnec-
essary waste generation [42]. Due to rapid mixing
velocity, the organic reaction is possible to be per-
formed in mild condition at ambient temperature thus cryogenic condition and usage of protecting groups could be avoided. The miniaturized device making this technology is feasible to be used as a portable system thus reducing the energy for chemicals distribution. It means that microfluidics served as an ideal reaction platform owing to high atom- and step-economical straightforward synthesis [41].

Organolithium compounds are known as highly reactive and pyrophoric compounds owing unstable carbon-lithium bonds. However, thank to merits of the microfluidics, organolithium reagents could be handled for an anionic Fries rearrangement (within a second), a catalyst-free amination of aromatic compounds (within a minute), a functionalization of 2,5-norbornadiene (within 3 minutes), a Suzuki-Miyaura cross-coupling reaction (within 5 minutes) and so on [44]. Furthermore, by using microfluidic technology, large-scale total synthesis of Pristane and Pauciflorol F compounds could be achieved within 5 minutes process, which was quite remarkable [43].

## 5. USAGE OF RENEWABLE FEEDSTOCKS

> "Feedstocks are better in renewable stage thus it could be stable either in technically or economically practice."

As the fossil material sources are depleting by years, renewable sources are more glimpsed and greatly utilized recently [45][46]. Plastics industry from the petroleum feedstocks is facing serious condition because the demand is much higher than the production rate. Because of that, several industries try to shift from petroleum-based polymer to biomass-derived polymer [46]. Preparation of biopolymer using an atom transfer radical (ATRP) polymerization had been known as an environmental-friendly method because it could be conducted in mild condition. Furthermore, by using a suitable catalyst material, the polymerization rate, polymerization degree and polymerization selectivity could be well controlled [47]. The catalyst material usually is built from an impregnation process on the silica materials making the process is cheap and convenient for the large-scale process. So far polylactide (polylactic acid) could be used to replace polystyrene and/or polyethene materials. It was because polylactide could be degraded easily in aerobic condition or under ultraviolet irradiation which was much easier than the degradation of either polystyrene or polyethene materials (> 1,000 years). Other

biomass-derived polymers such as polyglyconic acid and bio-polyethene have been commercially produced from sugar beet and biomass fermentation, respectively, delivering good news for our earth [48].

As the fossil-based material stock is diminished, researchers are developing biomaterials from waste oils [17]. Several biolubricants, biogreases, and biosurfactants have been designed and evaluated their possibility to be applied in the commercial process [49]. In our previous work, we utilized used frying

<figure><img src="image_10.png" /><figcaption>Figure 4. Structure of Biolubricant compound A-K.</figcaption></figure>

oil as the raw material to prepare cyclic ketal of 9,10-dihydroxyoctadecanoates, as well as other heterocyclic compounds [17][50][51][52]. At first, the used frying oil was transesterified, hydrolyzed, and then oxidized to obtain 9,10-dihydroxyoctadecanoic acid. That fatty acid was esterified and further reacted with carbonyl compounds to obtain the desired product. From that process, dioxane-dione (A), dioxepane (B), dioxolane (C, F-I), and dioxaspiro (D and E) compounds have been successfully prepared. Their chemical structures are shown in Figure 4 while their physicochemical properties are shown in Table 5.

From the physicochemical properties evaluation, the biolubricants A-E gave good density value, and much lower total acid number (TAN) and iodine value (IV) than either used frying oil or fossil-based lubricant, which was remarkable. Meanwhile, the total base number (TBN) is varied from low to medium due to the variance of the attached substituents on the heterocyclic moiety. On the other hand, biogreases F-I also give lower TAN and IV but
<table><caption>**Table 5.** Physicochemical properties of several biolubricants, biogreases, and biosurfactants synthesized from used frying oil waste [52].</caption><thead><tr><th rowspan="2">No</th><th rowspan="2">Compounds</th><th colspan="4">Physicochemical properties</th></tr><tr><th>Density (g/mL)</th><th>TAN (mg KOH/g)</th><th>TBN (mg KOH/g)</th><th>IV (mg I<sub>2</sub>/g)</th></tr></thead><tbody><tr><td>1</td><td>A</td><td>1.045</td><td>1.37</td><td>3.53</td><td>0.72</td></tr><tr><td>2</td><td>B</td><td>0.939</td><td>2.89</td><td>6.61</td><td>0.69</td></tr><tr><td>3</td><td>C</td><td>0.824</td><td>14.5</td><td>48.95</td><td>0.76</td></tr><tr><td>4</td><td>D</td><td>0.916</td><td>11.0</td><td>24.24</td><td>21.28</td></tr><tr><td>5</td><td>E</td><td>0.913</td><td>5.46</td><td>14.04</td><td>17.73</td></tr><tr><td>6</td><td>F</td><td>-</td><td>1.71</td><td>14.12</td><td>0.25</td></tr><tr><td>7</td><td>G</td><td>-</td><td>3.95</td><td>5.71</td><td>0.78</td></tr><tr><td>8</td><td>H</td><td>-</td><td>2.53</td><td>9.03</td><td>0.51</td></tr><tr><td>9</td><td>I</td><td>-</td><td>2.87</td><td>8.92</td><td>0.51</td></tr><tr><td>10</td><td>Used frying oil</td><td>0.910</td><td>7340</td><td>0.41</td><td>5380</td></tr><tr><td>11</td><td>Fossil-based lubricant</td><td>0.893</td><td>85.37</td><td>5.36</td><td>31.73</td></tr></tbody></table>

higher TBN demonstrating that they are potential to be applied as biomaterial for machine-based chemical processes [20]. Further utilization of plant oils is the preparation of nonionic biosurfactants J and K. From the investigation of their physicochemical properties, it was found that their surface tensions were 16.1 and 14.2 mN/m, their foam stability values for 100 mins were 3.0 and 42 mL, their critical micelle concentrations were 1.5 and 1.5 g/L, and while their emulsification indexes were 10.0 and 68.0% for 4 days observation, respectively. These physicochemical data show that the prepared nonionic biosurfactants are good candidates for industrial application [53].

## 6. CONCLUSIONS

As a conclusion, careful attention is very crucial to establish an efficient and effective design of organic synthesis process, as well as to maintain our environmental sustainability. This condition could be achieved by applying the green chemistry principles, i.e. 1) preventing of generated waste by observing the green chemistry quantitative metrics, 2) utilizing the safer and biofriendly solvents, 3) using a suitable synthesis method owing high energy efficiency, and 4) considering the use of renewable feedstocks such from the unused wastes. By that, there is no excuse to neglect the green chemistry perspective on running the chemical industries for

better future of our earth.

## AUTHOR INFORMATION

### Corresponding Author

**Yehezkiel Steven Kurniawan** — Ma Chung Research Center for Photosynthetic Pigments, Universitas Ma Chung, Malang-65151 (Indonesia);

orcid.org/0000-0002-4547-239X
Email: yehezkiel.steven@machung.ac.id

### Authors

**Krisfian Tata Aneka Priyangga** — Department of Chemistry, Universitas Gadjah Mada, Yogyakarta-55281 (Indonesia);

orcid.org/0000-0002-4119-2470

**Philip Anggo Krisbiantoro** — Graduate School of Environmental Science, Hokkaido University, Hokkaido-0600808 (Japan);

orcid.org/0000-0003-1712-175X

**Arif Cahyo Imawan** — Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei-10607 (Taiwan);

orcid.org/0000-0003-1910-7572

## ACKNOWLEDGEMENT

Yehezkiel Steven Kurniawan dedicated this review article for Mrs. Rahayu Linawati for her end-
less support and encourage so far.

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