lysinol: a renewably resourced alternative to petrochemical

LYSINOL: A RENEWABLY RESOURCED
ALTERNATIVE TO PETROCHEMICAL
ETHYLENEAMINES AND AMINOALCOHOLS
Kenneth G. Moloy, Pranit S. Metkar, & Mark A. Scialdone
Dupont Central Research and Development, Experimental Station
200 Powder Mill Road, Wilmington, DE 19803, USA
Lysine
OH
HO
HO
O
OH
OH
also alcohols,
acetate, etc.
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Corynebacterium
glutamicum
H 2N
CO2H
NH2
L-Lysine
Second largest production volume of any amino acid (glutamic acid/MSG #1).
Essential amino acid, used almost exclusively as animal feed (swine, poultry).
50 Year old fermentation process from glucose:
– Net 4 e- reduction, selectively break five C-OH bonds, selectively make two
C-NH2 bonds.
High yield: ~ 0.5 g lysine-HCl/g glucose vs. 0.56 g/g theoretical yield (90%).
Commodity volumes: ca. 2x109 kg per year and continues to grow.
Cheap
“Lysine” = lysine monohydrochloride, 80 % lysine content
– Lysine sulfate and lysine free base (50 % aq solution) are also available albeit in
smaller production volume.
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Lysine Economics
Global Lysine Production
US Lysine-HCl Price
3.0
2500
Estimate:
$2/kg market price,
$1.5/kg cost of
manufacture.
2.5
2000
2.0
1500
$/kg 1.5
kt
1000
500
0
1960
China:
ca. $2/kg average (2012)
$0.85/kg April 2014
1.0
0.5
1980
2000
2020
0.0
1995
2000
2005
2010
2015
Ongoing capacity increases in the Asia, US, Brazil, and Russia despite price pressure.
Capacity increases accompanied by significant R&D to further reduce cost.
Ajinomoto multigenerational lysine R&D
Lysine from non-food sources
“cellulosic lysine”
http://www.ajinomoto.com/csr/earth/climate.html
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Lysine as a chemical intermediate: Polyamides
H 2N
NH2
1,5-pentanediamine
CO2
H 2N
NH
+
NH3
α
-aminocaprolactam
zwitterion structure
limits reactivity
Nylon 5,# copolymers
Ajinomoto/Toray, Cathay, others
O
-
H 2N
Diacid
H 2N
CO2H
5-aminovaleric acid
Nylon 6 (via caprolactam)
Frost (Amyris), WO2005/123669A1
Wicks (Draths), WO2010/011967A1
Nylon 5
Pukin, et al., J. Mol. Catal. B: Enzym., 2010
?
H 2N
OH
NH2
Lysinol
(2,6-diamino-1-hexanol)
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Lysinol: Literature
 Only 23 unique citations refer to lysinol (S, R, or rac),
derivatives, or salts.
 A single reference describes the synthesis, isolation, and
characterization of lysinol free base.
 Literature examples are limited to multi-step, stoichiometric
conversion of lysine.
H 2N
CO2H 1) CBz-Cl
2) BH3
NH2
CBzHN
CH2OH
NHCBz
H2, Pd/C
H 2N
CH2OH
NH2
Kihara, et al., J. Polym. Sci., Part A: Polym. Chem., 1996, 34, 2173.
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Amino Acids to Amino Alcohols
Carboxylic acids and esters are not easily hydrogenated:
Ru/C
RCO2R' + H2
RCH2OH + R'OH
Catalyst Selection Guide, Johnson Matthey, 2007;
200-280 °C
200-300 bar
Manyar, et al., Chem. Commun., 2010, 46, 6279
Amino acids are easier - at acidic pH:
H
+
NH3
R
+
NH3
pH < 3
-
CO2
pH 4-8
+
R
CO2H
activated toward
reduction
+
H2
Ru/C
100-180 °C
35-100 bar
NH3
R
CH2OH
Examples for alanine, serine,
valine, leucine, proline,…
but not lysine.
K. P. Pimparkar; D. J. Miller; J. E. Jackson, Ind. Eng. Chem. Res. 2008, 47, 7648
F. T. Jere; J. E. Jackson; D. J. Miller, D. Ind. Eng. Chem. Res. 2004, 43, 3297
Urtel, et al., WO2005077871 (BASF)
Antons, et al., WO9938838 (Bayer)
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Lysine Hydrogenation
Conditions:
• 5 % Ru/C
• 100-120 °C
• 50-70 bar
• 20-30 wt% lysine in water
• Initial pH ~ 1.8-2 (~1.1 eq H2SO4)
NH2
H 2N
lysine
NH2
OH
2 H2
CO2H -H O H2N
2
lysinol
crude
product
Results:
• Quantitative lysine conversion
• 90+ % lysinol selectivity
• 50-70 % isolated yields of high purity
lysinol
1) OH2) remove Na2SO4
3) distill
Feed Grade
lysine also
works:
Lys-HCl
Lys-sulfate
50% aq base
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Product Distribution
NH2
+
2H
H2 N
CO2H
lysine
-H2O
2 H2
+
2H
NH2
OH
H2 N
lysinol
T > ~ 130 °C
pHi < ~ 1.5
- H2 O
+ H2
- NH4
NH2
+
H
N
H
piperidine
+
- CO
- H2
H2 N
OH
N
H
2-hydroxymethylpiperidine
2,5-diaminohexane
- NH4
- H2 O
+ H2
+ NH3
- H2 O
N
H
H
2H
+
NH2
+
2H
H
N
H
+ H2
- NH3
H
+
+
NH2
1-aminohexane
2-aminomethylpiperidine
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Hydrogenation Kinetics
1st order in H2
1st order in catalyst
0 order in lysine
Alanine hydrogenation kinetics: Jere, F.
T.; Jackson, J. E.; Miller, D. J. Ind. Eng.
Chem. Res., 2004, 43, 3297
NH2
H 2N
CO2H
H 2N
pKa1= 2.2 pKa2 = 8.8 pKa3= 10.5
NH2
OH
pKa1= 10.5 pKa2 = 12.8
Lysinol is a stronger base than lysine
 pH increases with increasing conversion
Initial pH
1.3
2.2
Final pH
3.5
6.9
Conv
>99%
75 %
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Catalyst Recycle
Hydrogenation rates are relatively low, large catalyst charges are used to
reduce batch time.
Catalyst is routinely recovered and reused.
Filtrate [Ru] is
below detection
limits (< 1 ppm)
3 g lysine (10 % aq), 1.1 equiv H2SO4, pHi = 1.7; 1 g 5%
Ru/C, 120 °C, 65 bar H2, 16 h.
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Stereoretention: Mosher amide & 19F NMR
H3CO
NH2
CF3
Cl
OH + 2
H2 N
O
S-Mosher's acid
chloride
S-lysinol
iPr
F 3C R
H3CO
Ph
O
S N
H
N
H
-71.39
F 3C R
H3CO
-71.40
R CF3
Ph
OCH3
-71.45
HO
O
Ph
N
H
RSR
2EtN
HO
O
S-lysine product
+
S-Mosher chloride
O
R N
H
R CF3
Ph
OCH3
-71.36
Result via peak deconvolution:
88-96 % ee, stereochemistry largely retained
rac-lysine product
+
S-Mosher chloride
1:1 RSR:RRR
R-lysine product
+
S-Mosher chloride
RRR
ppm
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Lysinol Polyamides
O
O
NH2
OH HO
H 2N
R
OH
HO
O
N
H
- H 2O
O
N
H
R n
Lysinol:adipic acid (R= (CH2)4) copolymer is insoluble, cannot be melt processed.
Example
Mole
%
lysinol
Mole
%
HMD
Nylon 66
5%
0
5
100
95
22800
10%
15%
20%
10
15
20
90
85
80
6704
insol
insol
Mn
Mz
PDI
1st
mp,
°C
2nd
mp,
°C
70330
502000
2
3.1
264
253
250
1630
28450
2.4
244
231
215
236
222
206
Mw
Conclusion: Cross-linking occurs via ester formation, therefore lysinol
based thermoplastic polyamides are not accessible.
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Polyfunctional Amines
NH3
+
O
1) reaction
H2 N
2) distillation
HN
N
OH
2
1) NH3/catalyst
2) distillation
OH
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Triamines
Cl
Ethanolamines
OH
Diamines
NH3
+
NH2
H2 N
2) caustic
3) distillation Tetraamines
H2 N
N
H
NH2
N
N
NH
HN
NH2
H
N
H2 N
Lysinol
HN
H
N
1) reaction
Cl
Complex product mixtures
Hazardous raw materials
Petrochemical-based
NH2
Ethyleneamines
NH2
N
N
H2 N
HN
3
N
NH2
N
H
N
N
NH2
NH2
H 2N
OH
Similar functionality,
structure, and
molecular weight
H2 N
H
N
Pentaamines
N
H
H
N
NH2
N
H2 N
NH2
H2 N
N
N
H
NH2
HN
N
H
N
N
H
N
NH2
NH2
N
H
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Ethanolamines, Ethyleneamines
Pricing: Ethanolamines ~ $1.9/kg; Ethyleneamines ~ $ 4.5-5.5/kg
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Ethyleneamine Markets
Global production: 2x109 kg/yr
Chemical Intermediates
Polyamide/Epoxy
Chelants
Fungicides
Lube Oils
Bleach Activator
Paper Resins
Piperazine Derivatives
Oil Field Chemicals
Urethanes
Surfactants
Fabric Softeners
Asphalt
Fuel Additives
amine ‘hardener’
OH
O
O
O
O
O
O
n
BADGE
NH2
OH + 2
H2 N
OH
N
X
N
OH
X
O
OH
X
OH
N
OH
N
OH
X
OH
O
X
N
OH
N
OH
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Epoxy Thermosets: Lysinol vs. Ethyleneamine (DETA)
Formulated at 1 NH per epoxy
Tack-free after several hours @ RT
Cured @ 60-100 °C
Thermoset properties are nearly
indistinguishable
Lysinol
Diethylenetriamine
4.6(1.1)
4.7(0.5)
Compression Modulus, MPa
1678(133)
1489(69)
Strain at Yield, %
11.6(0.5)
16.3(0.4)
Stress at Yield, MPa
103(1)
104(1)
Instrumented Hardness, MPa
228(48)
199(35)
Reduced Modulus, MPa
3506(412)
3287(279)
50% aq NaOH
5.5(2.5)
5.0(1.1)
30% aq H2SO4
3.8(1.0)
4.4(0.5)
H2O
2.4(0.2)
2.3(0.4)
3.5% aq NaCl
2.6(0.3)
1.9(1.5)
acetone
6.9(2.3)
5.4(1.9)
toluene
0.4(0.1)
0.2(0.4)
Lap Shear
Tensile Strength, MPa
Compression
Nanoindentation
TGA
DETA
lysinol
Chemical Resistance, % mass gain
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Other polymers from lysinol
Polyurea/polyurethane thermoset
O
R
NH2
OCN
OH
H 2N
R
O
NCO
N
H
N
H
O
O
N
H
N
H
N
H
R
n
Polyimide (solution processible)
NH2
OH
H 2N
O
O
O
+
O
O
OH
N
H
O
N
H
HO2C
OH
O
N
CO2H
O
O
N
O
O
O
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Take home message
Lysine and lysinol are worth our attention!
Renewable, inexpensive, abundant and non-toxic raw materials
Water solvent and co-product
High selectivity catalysis
Acknowledgments
Mark Scialdone
Pranit Metkar
Ellen Baldassare
Charlie Bellini
Jan Hytrek
Bryan Cheng
Dupont CR&D
Joe Bozell for
1) reading my paper and
2) inviting me to share my work
at this conference
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