István T.

Horváth - BMEVEKFM210

ENVIRONMENTALLY BENIGN AND CATALYTIC PROCESSES

KFM210
2020-21, Fall Semester, Friday 8:30 – 11:00

2. GREEN REACTIONS AND SOLVENTS

08:45 – 09:00 Introduction

October 16 09:15 – 10:00 Green reactions and solvents
10:15 – 11:00 Green energy

István T. Horváth

Department of Chemical and Environmental Process Engineering

istvan.t.horvath@edu.bme.hu
istvan.t.horvath@att.net

POLLUTION PREVENTION ACT OF 1990, USA

Changing the environmental risk paradigm

Remove the hazard at source instead of relying
on the “end-of-pipe” solution.
Eliminate or reduce the hazard, there is less
need to worry about the exposure!

GREEN CHEMISTRY

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GREEN CHEMISTRY

Green chemistry is the utilization of a set of principles that reduces

or eliminates the use or generation of hazardous substances in the
design, manufacture, and applications of chemical products.

Anastas, P. T.; Warner, J. C. Green Chemistry: Theory and Practice, Oxford University Press, Oxford, 1998.

THE 12 PRINCIPLES OF GREEN CHEMISTRY

1. It is better to prevent waste than to treat or clean up waste after it is
formed.
2. Synthetic methods should be designed to maximize the incorporation
of all materials used in the process into the final product.
3. Wherever practicable, synthetic methodologies should be designed to
use and generate substances that process little or no toxicity to
human health and the environment.
4. Chemical products should be designed to preserve efficacy of
function while reducing toxicity.
5. The use of auxiliary substances (e.g. solvents, separation agents, etc.)
should be made unnecessary wherever possible and, innocuous when
used.
6. Energy requirements should be recognized for their environmental
and economic impacts and should be minimized. Synthetic methods
should be conducted at ambient temperature and pressure.
Anastas, P. T.; Warner, J. C. Green Chemistry: Theory and Practice, Oxford University Press, Oxford, 1998

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THE 12 PRINCIPLES OF GREEN CHEMISTRY

7. A raw material of feedstock should be renewable rather than depleting
wherever technically and economically practicable.
8. Unnecessary derivatization (blocking group, protection/deprotection,
temporary modification of physical/chemical processes) should be
avoided whenever possible.
9. Catalysts (as selective as possible) are superior to reagents.
10. Chemical products should be designed so that at the end of their function
they do not persist in the environment and break down into innocuous
degradation products.
11. Analytical methodologies need to be further developed to allow for real-
time, in-process monitoring and control prior to the formation of
hazardous substances.
12. Substances and the form of a substance used in a chemical process
should be chosen so as to minimize the potential for chemical accidents,
including releases, explosion, and fires.
Anastas, P. T.; Warner, J. C. Green Chemistry: Theory and Practice, Oxford University Press, Oxford, 1998

ENVIRONMENTAL
ENVIRONMENTAL FACTOR*
FACTOR*
kg side-product / kg product

Product (t) E-factor

Petrochemicals 106 – 108 ~ 0.1

Basic chemicals 104 – 106 1-5

Fine chemicals 12 – 104 5 - 50

Pharmaceuticals 101-103 25 - 100+

*Roger A Sheldon, Chem. Ind. (London) 1992, 903.

C2H4 + Cl2 + Ca(OH)2 C2H4O + CaCl2 + H2O

44 111 18

E = 111 + 18 = 2.93
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ATOM ECONOMY

Hawaiian sepiolid squid

Euprymna scolopes

CH2=CH2 + Cl2 + H2O Cl-CH2-CH2-OH + HCl

O
Cl-CH2-CH2-OH + Ca(OH)2 + HCl H2C CH2 + CaCl 2 + 2 H2O

Catalyst O
CH2=CH2 + 1/2 O2
H2C CH2

Atom economy: 100%

Trost, B. Science, 1991, 254 (December 6), 1471.

GREEN SYNTHESIS OF ADIPIC ACID

Nylon 66 (DuPont, 1935)

• The first "sucessful" plastic

• Broad applications

• Polycondenzation of adipic acid

and hexamethylenediamine

– (n–1) H2O
n HOOC–(CH2)4–COOH + n H2N–(CH2)6–NH2
Adipic acid Hexamethylene-diamine

–C(O)NH–(CH2)6–NHC(O)–(CH2)4–C(O)NH–
n
Nylon 66

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SYNTHESIS OF ADIPIC ACID

Industrial synthesis

COOH
3 + 8 KMnO4 + 4 H2O 3 + 8 KOH + 8 MnO2
COOH
Waste!!!

Green synthesis1

kat. Na2WO4
kat. Aliquat 336 COOH
+ 4 H2O2 + 4 H2 O
KHSO4 COOH

[1] K. Sato, M. Aoki, and R. Noyori, “A ‘Green’ Route to Adipic Acid: Direct Oxidation of Cyclohexenes with 30
Percent Hydroxide Peroxide”, Science 1998, 281, 1646.

ATOMECONOMY
Industrial Synthesis
3 C6H10 + 8 KMnO4 + 4 H2O → 3 C6H10O4 + 8 KOH + 8 MnO2 Eatom

M = 82 M = 157 M = 18 M = 146 M = 56 M = 87 28%

Green Synthesis
3 C6H10 + 4 H2O2 → 3 C6H10O4 + 4 H2O Eatom

M = 82 M = 34 M = 146 M = 18 67%

The green synthesis

• Increased atomeconomy
• Less Waste
• Safer
• Catalytic

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ATOM ECONOMY

Rearrangements
By definition, a rearrangement reaction is a reorganization of the atoms that
make up a molecule. Therefore, by necessity, it is a 100% atom economical
reaction, where all the reactants are incorporated into the product

Addition
Because addition reactions add the elements of the reactant to a substrate
with total inclusion (e.g. bromination of olefins) they are atomic economical.

Substitution
When a substitution reaction is effected, the substituting group displaces a
leaving group. The leaving group is necessarily a waste product of the
reaction that is not included in the final product and therefore diminishes
the atom economy of the transformation.

Elimination
Elimination reactions transform the substrate by reducing the atoms to
generate the final product. In this case, any reagents used do not become
part of the final product and the eliminated atoms are lost as waste. This is,
therefore, intrinsically the least atom economical of the basic synthetic
transformations.

Rearrangement Reactions
Y Y
Can be effected by

A B 1. heat
A B
2. light
3. catalyst

Cope Rearrangement
R R
heat

Additional questions to ask

What is the conversion to the product?
Are there side reactions?
What energy input is required?

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Addition Reactions

Br

Br2 +

Br

O
Et OMgBr BrMgO Et
EtMgBr +
+
Ph CH3 Ph CH3 Ph CH3

O CN O

HCN +
OEt OEt

Pericyclic Reactions
O

O
+ O

O
O

CO2Et

+ N CO2Et
N
O
O
CO2Et
CO2Et

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Substitution Reactions

By nature are non-atom economical

A-B + C-D  A-D + B-C

Planned by-product
Is a catalyst required?
Accelerate reaction
Specificity

SN2 Reactions
SN1 Reactions

Substitution Reactions

Cl + KCN + KCl
CN

R R1 R R1

I NaOMe OMe + NaI

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Electrophilic Aromatic Substitution

H O
CH3
+ + HCl
Cl CH3

F NH2
+ NH3 + HF

Friedel-Crafts alkylations and acylations generally require Lewis acids (AlCl3, BF3)
Highly active “catalysts” lead to more by-products.

Elimination Reactions

By nature are non-atom economical

Planned co-product
R R

A A
+
B B
R'
R'

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Elimination Reactions

Utilized weight of Unutilized Weight of

Reagent MW
atoms utilized atoms atoms unutilized atoms
7 C4H9Br 137 4C,8H 56 HBr 81
8 C2H5ONa 68 ____ 0 2C,5H,O,Na 68
Total
205 4C,8H 56 2C,6H,O,Br,Na 149
6C,14H,O,Br,Na

% Atom Economy = (weight of atoms utilized/weight of all reactants) X 100

= (56/205) X 100 = 27%

A PERSONAL JOURNEY FROM SOLVENT TO SOLVENT

Horváth, I. T. Green Chem., 2008, 10, 1024–1028.

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SOLVENTS

Solvents are important components of Nature

to provide one or more liquid phases for
chemical reactions and processes.

While some solvents are available from Nature

even in large quantities, most of the solvents
are man-made.

Historically, solvents were developed and/or selected to

help the chemical or physical objectives of the users only.

With the increasing importance of local and global health

and environmental issues, the potential impacts of
solvents became important selection tools.

SOLVENTS IN CHEMISTRY

Advantages of Solvents

- Get molecules into a common phase where they can react.

- Dissolve solids so that they can be pumped.
- Lower viscosity and facilitate mixing.
- Regulate temperatures of reactions by heating at reflux.
- Moderate the vigor of exothermic reactions.
- Allow recovery of solids by filtration or centrifugation.
- Extract compounds from mixtures.
- Purify compounds by re-crystallization.
- Convert pyrophoric materials to less pyrophoric solutions
(as for aluminum alkyls).

- …..and more…..and more……

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SOLVENTS IN CHEMISTRY

Disadvantages of Solvents

- Loss of 10-15 million tons of solvents (with a fuel value

of $2 billion) each year.
- Destruction of upper atmosphere ozone by freons.
- Toxicity of chlorinated and other solvents to workers.
- Fires and explosions.
- Solvents cost money!

The United States uses 160 billion gallons of solvents each year.
The largest single use is for vapor degreasing, followed by dry
cleaning of clothes, then by immersion cleaning of parts.

WORKING WITH(OUT) SOLVENTS

A tiered approach from the least change to the most change

- Destroy or recover the solvent at source.

- Enclose the operation so that little if any solvent is lost.
- Substitute with a less harmful solvent.
- Use no solvent.
- Switch to a process that eliminates the need for a solvent.
- Can we do as well without the product made with solvents?

WORKING WITH DESIGNER SOLVENTS

The designer selects the solvent

Match solvent properties with chemical objectives.

Identify the best available solvent (or design a new solvent).

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FDA GUIDELINES ON SOLVENT USE

Based on the amounts of residual solvents (ppm), which are considered safe

• Class 1 solvents: Solvents should be avoided

• Benzene (2 ppm), tetrachlorocarbon (4 ppm),1,2-dichloroethane
(5 ppm), 1,1-dichloroethane (8 ppm), etc
• Class 2 solvents: Solvents to be limited (residues in the product
subject to regulations)
Hexane (290 ppm), toluene (890) ppm), 1,4-dioxane (380 ppm),
dichloromethane (600 ppm), pyridine (200 ppm), methanol
(3,000)
• Class 3 solvents: Solvents with low toxic potentials
acetic acid, acetone, ethanol, t-butyl alcohol, t-butyl methyl
ether, ethyl acetate, formic acid, heptane, pentane,

www.fda.gov/cder/guidance/index.htm

GREEN SOLVENTS

• Low or no reactivity & toxicity

• Easy recyclability (no disposal)

• Easy separation from product

(and reagent or catalyst)

• Biodegradable

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LIQUID-LIQUID BIPHASE CHEMISTRY

Allows the use of highly selective solution chemistry with the added
benefit of easy separation of the product from the reagent or catalyst.

Product phase
cA cB cP P
A+B
L
cA cB
REAGENT
cP
L or L
CATALYST

L
Reagent/Catalyst phase L=solubilizing group

The solvent properties of the products govern the selection of the

reagent/catalyst phase.
- Water
- Alcohols Apolar Products
- Ionic liquids
- Fluorous liquids Polar Products
- Supercritical CO2

AQUEOUS-PHASE SOLUBLE RHODIUM-PHOSPHINE

CATALYST FOR OLEFIN HYDROFORMYLATION
Ruhrchemie/Rhône-Poulenc Process

600 - 800 psi CO/H2, 125oC, P:Rh <100

O CH3 O
CH3 CH2 CH2 + CO + H2 CH3CH2CH2C + CH C
H CH3 H
normal iso

H Advantages
P Easy separation of the products
P Rh High n/i selectivity
P
C Disadvantages
O
Olefin solubility limitations
P = P

SO3Na Rideout, D. C.; Breslow, R. J.

3 JACS 1980, 102, 7816.
E. Kuntz, French Patent 2 314 910 (1975) Diels-Alder cycloaddition in water

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RUHRCHEMIE/RHONE-POULENC OXO PROCESS

HRh(CO)[P(C6H4SO3Na)3]3 in water, 110-130°C, 40-60 bar CO/H2 (1:1)

exhaust gas

olefin
separator

syngas
phase
reactor separator

stripping
column

water

heat exchanger crude aldehyde

steam
Angev. Chem. Int. Ed. Eng. 1993. 32. 1524-1544

Ruhrchemie/Rhone-Poluenc oxo process, developed by E. Kuntz and commercialized by B.

Cornils, uses water as the catalyst phase and a rhodium catalyst modified with the water
soluble P(m-C6H4SO3Na)3
While propylene is highly soluble in water, the butanals phase separate from the catalyst
phase
The typical size of a Ruhrchemie/Rhone-Poluenc oxo plant is 150,00 tons per year

SHELL HIGHER OLEFIN PROCESS (SHOP)

P
NiH
O
(n + 2 ) H C CH C H C H (C H C H ) C H CH
2 2 3 2 2 2 n 2
1 ,4 -buta ne diol
a -ole fins

Limited miscibility
with butane diol

Ph Ph
Ph Ph
P P P
NiH = or
Ni H Ni H
O
O O O
Ph

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SHELL HIGHER OLEFIN PROCESS (SHOP)

Ni(R2PCH2COOH)LX in 1,4-butanediol, 80-120°C, 1500 psi ethylene

recycle

lights to methathesis

ethylene
alkenes

catalyst
C6 - C20 1-alkenes

heavy to methathesis
products

solvent solvent
catalyst bleed
Reactor Separator Distillation Columns
Alkene wash /
solvent purification

SHOP was developed by W. Keim, uses butanediol as the catalyst phase and a nickel catalyst
modified with a diol soluble phosphine R2PCH2COOH.
While ethylene is highly soluble in butanediol, the higher olefins phase separate from the
catalyst phase.
The typical size of a SHOP plant is 250,00 tons per year.

IONIC LIQUIDS

CATIONS ANIONS
BF4 , PF6-, SbF6-, NO3-
-

R1 R1 CF3SO3-, (CF3SO3)2N-,
N P N N N ArSO3-, CF3CO2-, CH3CO2-,
R2 R2 R1 R2
R3 R3 R3 R3 Al2Cl7-
R

+ Liquid range of 300oC

+ Good solvents for a wide range of meterials
+ No effective vapor pressure
+ Good thermal stability up to 200oC
+ Tunable acidity
+ Relatively cheap and easy to prepare
- Water sensitivity could be an issue
- Health and environmental issues ?

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DSM’S CAPROLACTAM PROCESS

Cyclohexanone
Oxime

NH 3

CAPL
100-110°C
Oleum
Ammonium Sulfate

The reaction is performed in the so called rearrangement mixture.

- Liquid cyclohexanone oxim is used.

- The ratio of H2SO4/SO3 to cyclohexanone oxime is 1.7
- The amount of maximum free SO3 is 12 mol%.
- 100% conversion and 99.5% selectivity
- Ammonium sulfate is the by-product.
- The heat of reaction is about – 65 kcal/mol (hot spots potentials).
- The concentration of SO3 has a strong influence on the reaction rate.

DSM PROCESS
The reaction medium (or the „rearrangement mixture”) is the mixture
of e-caprolactam and oleum, which is actually an ionic liquid.

The DSM process therfore the oldest and greatest chemical

technology performed in an ionic liquid.
O OH
H 2 SO 4 HS O 4
NH NH

C=O a b c e d

1 mmol in 6.84 mmol 10% Oleum

1 mmol in 6 mmol 97% H2SO4

H2
C
H2C c e d CH2

H2C a b CH2

NH C
1 mmol in 0.6 mLCDCl3

180 170 160

O
150 140 130 120 110 100 90 80 70 60 50 40 30 20
High viscosity !!!
(ppm)

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H2SO4/CAPROLACTAM = 1.1 MIXTURE

AT ROOM TEMPERATURE

H2SO4+SO3/CAPROLACTAM = 1.5 MIXTURE

AT ROOM TEMPERATURE

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H2SO4+SO3/CAPROLACTAM = 2.1 MIXTURE

AT ROOM TEMPERATURE

TEMPERATURE DEPENDENT VAPOR PRESSURE

60

Oleum
50

40
Vapor pressure (kPa)

30

20

10

0
0 20 40 60 80 100 120 140 160
Temperaure (°C)

CAPL/H2SO4=1:1 (■), CAPL/H2SO4/SO3=3.3:4.7:1 (●), and H2SO4/SO3=12:1 (▲)

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e-CAPROLACTAMIUM HYDROSULFATE
What is the reason for the low vapor pressure of dissolved SO3?

O OH
H2SO4 HSO4
NH NH

OH OH

HSO4 SO3 HS2O7

NH NH

Fábos, V.; Lantos, D.; Bodor, A.; Bálint, A.-M.; Mika, L. T.; Sielcken, O. E., Cuiper,
A.; Horváth, I. T. ChemSusChem. 2008, 1, 189-192.

°C
C2H4 50
C2H6 Xe
SF6
SF6
40
50 C2H6
CO2 30
CO2

20
25 75 Xe

Bar C2H4 10

Pc Tc

Schematic presentation of the critical temperatures (Tc) and critical pressure (Pc)
of the selected pure materials with critical points near room tempetature

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SUPERCRITICAL CARBON DIOXIDE

METATHESIS IN SUPERCRITICAL CARBON DIOXIDE

O
O
O
O
ADMET RCM
Polymer + CH2=CH2

Y (%)
100 F3C
Ph
F3C
PCy3 80
RCM
Cl Ru O R
60 M
Cl R O N
PCy3
40
F3C
20 F3C R
ADMET
0

0.55 0.65 0.75 0.85  (g/ml)

Fustner, A. et al. Angew. Chem. Int. Ed. Engl. 1997, 36, 2466.

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