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Current Green Chemistry, 2021, 8, 179-184

PERSPECTIVE
ISSN: 2213-3461
eISSN: 2213-347X

Trends and Possibilities to Turn Industrial Organic Chemistry Greener

BENTHAM
SCIENCE

György Keglevich1,*

1
Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, 1521 Budapest,
Hungary
ARTICLE HISTORY
1. INTRODUCTION
Received: September 22, 2021
Revised: October 02, 2021
These days, chemists can do much to save our planet. On the one hand, a lot depends on the kind
Accepted: October 02, 2021 of products (plastics, washing powders, dyes, plant protecting agents, pharmaceuticals, etc.) that are
developed and the kind of technologies applied during their processing. Are the procedures environ-
DOI:
10.2174/2213346108666211021161235 mentally friendly? On the other hand, it is important to shape a suitable view at the different levels of
education regarding the rational use of the products mentioned above from the point of view of sus-
tainability. An important issue is the prevention of the spilling of air, field, and water reservoirs and
the promotion of recirculation. At the same time, education should be extended to compensate for the
chemophobia that is present in society. This perspective should provide a few points of view on the solution to the problems
mentioned above.
2. RENEWABLE SOURCES AS STARTING MATERIALS
From among the 12 principles of green chemistry [1], one of the most important items is that the starting materials of syn-
theses should derive from the renewable pool. The alcoholic fermentation of glucose deriving from the acidic hydrolysis of
cellulose leads to ethyl alcohol that may be used as starting material or as fuel. This already applied method will spread in the
future. The circle started by photosynthesis is shown in Fig. (1) [2]. It is noted that Nobel Prize winner G. Oláh envisaged a
methyl alcohol-based industry [3]. However, the toxicity of methyl alcohol may limit its application, e.g., to the accumulator
mobile phones.
Current Green Chemistry

Fig. (1). The “ethyl alcohol cycle” – biosynthesis and utilization.

Returning to bio-based ethyl alcohol, a larger amount is produced from corn, and it is mixed into fuels obtained from petro-
chemical sources. The proportion of the bio-based component is ≥10%. The compulsory corn quote required from the farmers
in the States often generates problems between the government and them, as selling the corn in the food industry or as fodder
for animals would be more rentable.

*Address correspondence to this author at the Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, 1521
Budapest, Hungary; Tel: +36-1-463-1111(5883); E-mail: keglevich.gyorgy@vbk.mail.bme.hu

2213-347X/21 © 2021 Bentham Science Publishers

180 Current Green Chemistry, 2021, Vol. 8, No. 3 György Keglevich

3. ATOMIC EFFICIENT CHEMICAL TRANSFORMATIONS

The other important criterion in green chemistry is that atomic efficient chemical reactions should be selected. Such trans-
formations are additions, isomerizations, rearrangements, and polymerizations. Let us regard the synthesis of phenol via the
rearrangement of the hydroperoxide of cumene (Scheme 1), the syntheses of salicylic acid by the Kolbe–Schmitt reaction
(Scheme 2), the formation of the key-intermediate for paracetamol (Scheme 3), and the manufacturing of caprolactam (Scheme
4) that is also possible under green chemical conditions [4].

Scheme (1). Synthesis of phenol via the rearrangement of the hydroperoxide of cumene.

Scheme (2). Synthesis of salicylic acid by the Kolbe–Schmitt procedure.

Scheme (3). Synthesis of the intermediate of paracetamol.

O N OH ~100 °C O
H2SO4
NH

Scheme (4). Industrial synthesis of caprolactam.

A number of atomic-efficient procedures are being applied in the industry, which is a trend to be welcome. A series of elim-
ination and condensation reactions involves the departure of water. Although in these cases the atomic efficiency is <100%, the
transformations under discussion may be regarded as environmentally friendly.
4. CATALYTIC CHEMICAL TRANSFORMATIONS
Perhaps the third most important criterion is to utilize selective catalytic reactions. In the presence of suitable catalysts, the bar-
rier meant by the activation enthalpy may decrease. There are many kinds of catalytic reactions; the two major groups include
heterogeneous and homogeneous processes. The first group may be exemplified by oxidations performed in the presence of air
or hydrogenations, while the other group may also include hydrogenations along with hydroformylations involving transition
metal-phosphine complexes as catalysts. The heterogeneous and homogeneous transformations are widely applied procedures
in the intermediate-, fine chemical- and pharmaceutical industries. A special field is phase transfer catalysis (PTC), allowing
organic chemical reactions in liquid-liquid and liquid-solid two-phase systems [5]. The catalysts may be quaternary onium salts
or crown ethers. PTC finds application in the pharmaceutical and plastic industry (e.g., during the synthesis of epoxy resins).
The green accomplishments involve catalysts bond to a solid carrier. In these cases, after use, the catalyst may be removed by
simple filtration, and then it can be re-used. Metal-free organocatalysts have become more and more important. In case the cata-
lyst is of optical activity, it may promote enantioselective syntheses. Either the P-ligand or the phase transfer catalyst, or the
organocatalyst may bear a center of chirality. In a longer range, enantioselective syntheses will substitute optical resolutions.
Preparation of pure enantiomers is requested not only in the pharmaceutical industry, but also in respect of plant-protecting
Trends and Possibilities to Turn Industrial Organic Chemistry Greener Current Green Chemistry, 2021, Vol. 8, No. 3 181

agents and cosmetics. A philosophical question emerges in connection with the application of catalysts. A lot of procedures
were developed that may be carried out at room temperature but in the presence of (often) special catalysts (A). In most cases,
the chemical transformations discussed may also be performed without any catalyst but at a higher temperature of 80-120 °C
(B). Which is the “greener” approach, A or B? Certainly, the “greener” protocol is that performed on heating, in the lack of any
catalyst. At the end of the procedure, all catalysts mean cost and environmental burden. At the same time, it remains an im-
portant green chemical recommendation that the transformations should be possibly realized at room temperature and at atmos-
pheric pressure.
5. THE PROBLEMATICS OF SOLVENT
Benzene, carbon tetrachloride, and chloroform are not applied in the industry as solvents anymore. At the same time, tolu-
ene and alcohols, especially butyl alcohol are good choices of solvents. Butyl acetate is better than ethyl acetate due to its high-
er boiling point and greater extent of lipophilicity if it is considered as an extractant. Although acetonitrile and acetone are
flammable and volatile, they are still tolerated in the industry. Diethyl ether (that is indispensable in Grignard reactions and
different metal-organic transformations) should be replaced by tetrahydrofuran (THF). The best solution is the application of
2-methyltetrahydrofuran obtained from biomass, as its boiling point is higher than that of THF (79 °C vs. 66 °C).
The application of water as the solvent with respect to organic reactions is not really relevant, as the organic reactants are
not soluble in water. Carbohydrates mean an exception, as, due to the hydroxy groups, they are soluble in water. α-D-glucose is
a useful starting material in a series of biotechnological transformations, such as in the synthesis of adipic acid. The
microorganism-promoted and enzyme-catalyzed transformations are the tools of the future. Returning to the aqueous medium,
the “on water” reactions are interesting, as in this case, water-insoluble substrates may be involved in efficient water-phase re-
actions [6].
Supercritical CO2 may be used as a solvent in HPLC separations, extractions, or in the separation of enantiomers.
Ionic liquids are considered green solvents as they are not volatile, and their properties may be fine-tuned by selecting a
suitable cation and anion. Ionic liquids find application as solvents in a few industrial procedures, such as in hydroformylations
(Scheme 5), in the preparation of dodecylbenzene (that is the starting material of dodecylbenzenesulfonate prepared in
>2 million tons/year (Scheme 6), and in the BASIL-technology (Scheme 7) [7].

Scheme (5). Hydoformylation in ionic liquid.

Scheme (6). The synthesis of dodecylbenzene using EtMeimim Al2Cl7.

Scheme (7). The BASIL-technology.

It seems to be probable that the ionic liquids will spread not as solvents, but as catalysts or additives promoting reactions
[8]. A good example may be the synthesis of dronic acid derivatives used as drugs against bone deceases. The reaction of the
suitably substituted acetic acid, phosphorus trichloride, and phosphorous acid in sulfolane may be enhanced by butyl-
methylimidazolium hexafluorophosphate. This is exemplified via the synthesis of zoledronate (Scheme 8) [9, 10].
 182 Current Green Chemistry, 2021, Vol. 8, No. 3 György Keglevich

Scheme (8). Efficient preparation of zoledronate in the presence of an ionic liquid additive.

Another example is the microwave (MW)-assisted direct esterification of phosphinic acids in the presence of suitable ionic
liquid additives. Under such conditions, the esterifications took place at lower temperatures, and under shorter reaction times
(Scheme 9) [11, 12].
R1 O MW R1 O
P + R3OH P
R2 OH 160-200 °C R2 OR3

R1 H Me Ph

R2 Ph Ph Ph

Scheme (9). Ionic liquid-promoted direct esterification of phosphinic acids under MW conditions.

6. MICROWAVE-ASSISTANCE
Enhancing reactions with MW irradiation is a “green” tool. The advantages include immediate heat transfer (1), faster, more
selective, and hence efficient reactions (2), and often solvent-free accomplishments (3) [13]. As a matter of fact, MW assistance
is ideal for promoting chemical transformations with high (ca. 130–180 kJ mol–1) enthalpy of activation (Fig. 2A). In the case
of exothermic reactions, MW irradiation is unnecessary (Fig. 2B), while endothermic conversions will remain incomplete even
under the effect of MWs (Fig. 2C) [14, 15].
Enthalpy

Enthalpy
Enthalpy

ΔH# Δ Δ
Δ ΔH#

Δ Δ ΔH#
ΔH0 Δ Δ ΔHΔ0
0 0 0
Δ Δ ΔH0

Reaction coordinate Reaction coordinate Reaction coordinate

(A) (B) (C)

Fig. (2). Typical enthalpy profiles for organic reactions.

The industrial application of MW reactors is limited by their small size that cannot be increased. If the reaction mixture is
not heterogeneous and not viscous, the flow chemical accomplishment may be a good solution [16]. It can be predicted that lots
of parallelly operated flow reactors may spread in the industry.
7. PHOSGENE CHEMISTRY
The replacement of carcinogen phosgene that is a basic starting material in the preparation of carbonic acid derivatives, such
as dialkyl carbonates, urethane derivatives, and carbamates (Scheme 10), is a real challenge. The chloroformic derivatives and
isocyanates are important intermediates. Dialkyl carbonates are alkylating agents, and recently they have been used as “green”
Trends and Possibilities to Turn Industrial Organic Chemistry Greener Current Green Chemistry, 2021, Vol. 8, No. 3 183

solvents [17], while the urethanes and carbamates are relevant in the plant protecting agent industry. Polyurethanes are typical
plastics.
COCl2
ROH
NH

O O in the case of
a sec. amine
RO C Cl N C Cl N C O
-HCl
ROH
ROH NH
ROH
O
(RO)2C O N 2C O
N C OR

Scheme (10). The phosgene “family tree.”

Traditionally, phosgene is synthesized by the reaction of carbon monoxide and chlorine on the surface of activated carbon,
which is not a “green” approach. Moreover, under normal conditions, phosgene is a gas that can be taken from a cylinder. A
good alternative is triphosgene, which has the formula (C3O3Cl6). It may be regarded as the trimer of phosgene. However, ac-
cording to chemical structure, it is, as a matter of fact, hexachlorodimethyl carbonate. It is prepared by the reaction of methyl
alcohol and carbon dioxide at a higher temperature and pressure. The dimethyl carbonate so obtained is then photochlorinated
(Scheme 11). Triphosgene is a user-friendly white solid material that behaves as phosgene.
hν
p, T Cl2
2 MeOH + CO2 (MeO)2C O (Cl3CO)2C O
-H2O

Scheme (11). Industrial processing of triphosgene.

Triphosgene is manufactured in China and India in particular, and they fulfill the need worldwide. There is no obstacle to
the spread of triphosgene. Triphosgene is suitable for converting carboxylic acids to acid chlorides and alcohols to alkyl-
chlorides (Scheme 12).

Scheme (12). Application of triphosgene in OH → Cl replacements.

CONCLUSION
The development of “greener” variations of organic reactions and technologies within the chemical industry is an actual
challenge. Ethyl alcohol has become an important starting material that may be obtained by the alcoholic fermentation of glu-
cose available by the acidic hydrolysis of cellulose. Where it is possible (the processing of salicylic acid, p-aminophenol, and
caprolactam), atomic-efficient transformations should be applied. Catalytic reactions comprising heterogeneous, homogeneous,
organocatalytic, and phase transfer catalytic transformations represent environmentally-friendly accomplishments. When
selecting solvents, the use of toluene, butyl alcohol, water, ionic liquids, and supercritical solvents should be considered. Ionic
liquids may also serve as catalysts. The application of MWs, especially in flow systems, may bring a breakthrough.
CONSENT FOR PUBLICATION
Not applicable.
FUNDING

This project was supported by the National Research, Development, and Innovation Office, Hungary (Grant No. K134318).
CONFLICT OF INTEREST
The author declares no conflict of interest, financial or otherwise.
184 Current Green Chemistry, 2021, Vol. 8, No. 3 György Keglevich

ACKNOWLEDGEMENTS
Declared none.
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