chemical product design how is it done?...2000-11-15-01 how is it done? molecular knowledge systems,...

Dr. Kevin G. Joback Molecular Knowledge Systems, Inc. [email protected]

Chemical Product Design How is it done?

2000-11-15-01

Molecular Knowledge Systems, Inc.

Molecular Knowledge Systems

Located in Bedford, New Hampshire Company Started in 1989 Computer Software Consulting

Emulsifier Phase

Oxygen Carrier

Continuous Phase

Substructure Search

{1} CO CH2O

C OO

CH2 {1}

{1} C OCH2O

C OO

CH2 {1}

Group Contributions

# Carbons

Boi

ling

Poin

t, K

Slope = 22.9-CH2-

SYNAPSE http://www.molecularknowledge.com

[email protected]

Design Chemical Products

SP, P

olar

SP, Hydrogen Bonding

-COO-

-CH3-CH2-

-CH2-

Select Solvents

A + B

A + S

B

A

S

Group Contributions

# Carbons

Boi

ling

Poin

t, K

Slope = 22.9-CH2-

Phase Equilibrium

Tem

pera

ture

, °C

wt% Depressant

Liquid&

Solid

Equations of State

)()( bVbbVVa

bVRTP

−++−

−=

2Va

bVRTP −−

=

+++= 21VC

VBZ

Estimate Properties

CH3

OH

CH2

CH

CH3

23.6

92.9

22.9

21.7

23.6

Tb = Σ ni ∆i

Substructure Search

{1} CO CH2O

C OO

CH2 {1}

{1} C OCH2O

C OO

CH2 {1}

Formulate Mixtures

Density

Viscosity

Solubility

Melt Point

Flash Point

20%

34%31%

15%

Group ContributionsGroup

-CH3-CH2--OH

>C=O-COO-

Intercept

∆SP,p

-0.591-0.3775.5484.6704.7295.067

∆SP,h

-0.848-0.59510.6304.8464.0127.229


-CH3-CH2--OH

>C=O-COO-

Intercept

∆SP,p

-0.591-0.3775.5484.6704.7295.067

∆SP,h

-0.848-0.59510.6304.8464.0127.229

Phase Equilibrium

Tem

pera

ture

, °C

wt% Depressant

Liquid&

Solid

Substructure Search

{1} CO CH2O

C OO

CH2 {1}

{1} C OCH2O

C OO

CH2 {1}

Group Contributions

# Carbons

Boi

ling

Poin

t, K

Slope = 22.9-CH2-

CRANIUM http://www.molecularknowledge.com

[email protected]

Design Chemical Products

SP, P

olar

SP, Hydrogen Bonding

-COO-

-CH3-CH2-

-CH2-

Select Solvents

A + B

A + S

B

A

S

Group Contributions

# Carbons

Boi

ling

Poin

t, K

Slope = 22.9-CH2-

Phase Equilibrium

Tem

pera

ture

, °C

wt% Depressant

Liquid&

Solid

Equations of State

)()( bVbbVVa

bVRTP

−++−

−=

2Va

bVRTP −−

=

+++= 21VC

VBZ

Estimate Properties

CH3

OH

CH2

CH

CH3

23.6

92.9

22.9

21.7

23.6

Tb = Σ ni ∆i

Substructure Search

{1} CO CH2O

C OO

CH2 {1}

{1} C OCH2O

C OO

CH2 {1}

Formulate Mixtures

Density

Viscosity

Solubility

Melt Point

Flash Point

20%

34%31%

15%


-CH3-CH2--OH

>C=O-COO-

Intercept

∆SP,p

-0.591-0.3775.5484.6704.7295.067

∆SP,h

-0.848-0.59510.6304.8464.0127.229


-CH3-CH2--OH

>C=O-COO-

Intercept

∆SP,p

-0.591-0.3775.5484.6704.7295.067

∆SP,h

-0.848-0.59510.6304.8464.0127.229

Phase Equilibrium

Tem

pera

ture

, °C

wt% Depressant

Liquid&

Solid

2000-11-15-01

How is it Done?


Sodium lauryl sulfate Propylene glycol Diazolidinyl urea Triethanolamine Methylparaben Propylparaben

Stearic acid Laureth-23 Fragrance Isobutane Propane

Water Aloe

Shaving Cream

How did they choose these chemicals?

2000-11-15-01

How is it Done?


Sodium lauryl sulfate Laureth-23

Propylene glycol Diazolidinyl urea Methylparaben Propylparaben

Triethanolamine Stearic acid Fragrance

Aloe Isobutane Propane

Water

Shaving Cream

“The goal of chemical product design is to create chemical structures and mixtures that possess those chemical and physical properties desired by

customers.”

Goal

Environmental friendly Skin lubrication Water solubility Pleasant aroma Hair softening Moisturizing Foaminess

2000-11-15-01

Design Steps

1. Compile Property Constraints: analysis

2. Generate Candidates: combination

3. Evaluate Properties: estimation


Chemical Product Design (3 Steps)

(refrigerants, solvents, anti-icing fluids)

2000-11-15-01

Designing New Refrigerants


Heat

Heat

Condenser

Evaporator

Next Generation Refrigerants

Single Component

F

F

F

F

C C

H

H

Replace R134a

2000-11-15-01

Design Steps







2000-11-15-01

Step 1: Property Constraints


Heat

Heat

Condenser

Evaporator

Next Generation Refrigerants

R134a Replacement Vapor Pressures Match

Low Global Warming

Not Ozone Depleting

P-H Diagrams Match

High Oil Solubility

Low Flammability

Low Toxicity

2000-11-15-01



Temperature [K]175.0 200.0 225.0 250.0 275.0 300.0 325.0 350.0

Vapo

r Pre

ssur

e [k

Pa]

1.00E+0

3.13E+2

6.26E+2

9.38E+2

1.25E+3

1.56E+3

1.88E+3

2.19E+3

2.50E+3

Pvp(280K) = 370.6 kPa Pvp(320K) = 1218.0 kPa

Which chemicals match R134a Vapor Pressures ?

2000-11-15-01

Design Steps







2000-11-15-01

Step 2: Generate Candidates

( -CH3 -CH3 ) ( -CH3 -CH2- ) ( -CH3 >CH- ) ( -CH3 =CH2 ) . . .


Combinations of 2

Combinations of 3 ( -CH3 -CH3 -CH3 ) ( -CH3 -CH3 -CH2- ) ( -CH3 -CH3 >CH- ) . . .

Group Basis

CH3 CH2

CH C

CH2 CH

O C

F

2000-11-15-01



Structure Enumeration

( -CH3 -CH3 -CH2- >C< >CH- -F -F -F )

CH3 CH3

F

F

F

CH2 CH C CH3

CH3

F

F

F

CH2 CH C CH3

CH3

F

F

F

CH2 CH C

CH3 CH3

F

F

F

CH2 CH C

CH3

CH3

F

F

F CH2 CH C CH3

CH3

F

F

F CH2 CH C

CH3 CH3

F

F F

CH2 CH C CH3

CH3

F

F

F

CH2 CH C CH3

CH3

F F

F CH2 CH C

CH3

CH3

F

F

F CH2 CH C

CH3

CH3

F

F

F

CH2 CH C

CH3

CH3

F F

F CH2 CH C

2000-11-15-01



Groups to Choose From

Groups in Molecule

Feasible Candidates

9 9 9 9 9

4 6 8 10 12

24 261

3,992 72,214 many

Possible Candidate Structures

2000-11-15-01


CH3-CH2-CH2-CH3 CH3-CH(CH3)-CH3 CH3-CH2-CH=CH2 CH3-CH=CH-CH3 CH2=CH-CH=CH2 CH2=C(CH3)-CH3 CH3-CH2-O-CH3

CH3-O-O-CH3 CH3-CH2-CH2-F CH3-CH(CH3)-F CH2=CH-CH2-F CH3-CH=CH-F


24 Valid Structures of 4 Groups Group Basis

CH3 CH2

CH C

CH2 CH

O C

F

CH2=C(CH3)-F CH3-CH2-O-F CH3-O-CH2-F CH2=CH-O-F CH3-O-O-F

F-CH2-CH2-F CH3-CH(F)-F F-CH=CH-F CH2=C(F)-F F-CH2-O-F

F-O-O-F F-CH(F)-F

2000-11-15-01

Design Steps







2000-11-15-01

Step 3: Evaluate Properties


CH3-CH2-CH2-CH3 CH3-CH(CH3)-CH3 CH3-CH2-CH=CH2 CH3-CH=CH-CH3 CH2=CH-CH=CH2 CH2=C(CH3)-CH3 CH3-CH2-O-CH3

Ozone Depletion Potential

Global Warming Potential

Vapor Pressures – f(T)

Flammability Limits

Rat LC50 4 Hours

Enthalpy – f(T,P)

Oil Solubility

Need to Screen Thousands of Candidates

2000-11-15-01


Group Contribution Techniques Equation Oriented Techniques Force Field Techniques Connectivity Indices Parameter Fits


Physical Property Estimation Techniques

2000-11-15-01

Group Contribution Techniques


Group ∆Tb

-CH3 -CH3 -CH2- >CH- -OH

23.6 23.6 22.9 21.7 92.9

Tb (est) 382.8 K Tb (lit) 372.7 K

CH3

OH

CH2

CH

CH3

1

3 2

4 1) Select Technique 2) Dissect Structure 3) Get Contributions 4) Insert into Model Tb = 198.1 + Σ∆i

2000-11-15-01

Boiling Point, Estimation Errors


(Estimate – Data) [K]

Perc

enta

ge

0

10

20

30

40

50

60

70

-120 -80 -40 0 40 80 120 160 200

Observations Avg Error Avg Abs Err Avg % Error Max Error

559 0.97 K 15.1 K 4.8 %

197.4 K

N-Methylformamide Acetamide Fluorine Cyanogen

-128.5 K -122.6 K 113.1 K 197.4 K

Statistics

Outliers, Errors

Joback’s Method

2000-11-15-01

Equation Oriented Techniques


Vapo

r Pre

ssur

e [M

Pa]

Temperature [K]

Vapor Pressure - Heptane

−

−=

rbr

cbr

c

vp

TTPT

PP 11

1)ln(ln

Required Properties

Tc – Critical Temperature

Pc – Critical Pressure

Tb – Boiling point 0.00

0.50

1.00

1.50

2.00

2.50

200 250 300 350 400 450 500 550

2000-11-15-01



Property Tb Tc Pc

Pvp (280 K) Pvp (320 K)

Estimate 238.4 K 366.7 K

3406 kPa 452 kPa

1291 kPa

CH2 C C

F F

F

F

Temperature [K]225.0 238.6 252.1 265.7 279.3 292.9 306.4 320.0

Vapo

r Pre

ssur

e [k

Pa]

1.00E+0

1.88E+2

3.76E+2

5.63E+2

7.51E+2

9.38E+2

1.13E+3

1.31E+3

1.50E+3

Candidate R 134a

R134a Pvp(280K) = 370.6 kPa R134a Pvp(320K) = 1218.0 kPa

2000-11-15-01



Candidate Refrigerants

Candidate Pvp (280K) Pvp (320K)

R 134a F-CHF-CHF-CH2-F F-CHF-O-CHF-F F-CF=CF-F F-CH2-CH2-F F-CHF-CH2-CHF-F CH3-CF2-CH3 CH2=CF-CF3

370.6 418.8 414.8 415.9 409.2 418.8 385.3 452.5

1218 1275 1299 1223 1233 1275 1114 1291

2000-11-15-01

Design Steps







2000-11-15-01

Solvents in Chemical Products

Evaporation rate Solute solubility Vapor pressure Freezing point Boiling point Flammability Recyclability

Viscosity Irritancy Toxicity Listed


Solvents Applications Personal Care Products Cosmetics / Fragrances Pesticides / Herbicides Cleaning / Degreasing Adhesives / Sealants

Process Solvents Paints / Coatings Pharmaceuticals

Printing Inks Detergents

Property Constraints

2000-11-15-01

Design Steps







2000-11-15-01



A. Beerbower, P. L. Wu and A. Martin. "Expanded Solubility Parameter Approach I: Naphthalene and Benzoic Acid in Individual Solvents." Journal of Pharmaceutical Sciences. Volume 73, number 2, page 179-188, 1984.

Solute = Benzoic Acid

Solubility at 25°C

Solvent Pyridine Dimethyl sulfoxide N,N-Dimethylformamide N,N-Dimethylacetamide N-Methylformamide Methanol Ethanol 2-Propanol

wt % 64.0 61.9 61.7 60.7 51.9 42.6 36.6 32.8

Could solvent blends give higher solubility?

2000-11-15-01



A. Beerbower, P. L. Wu and A. Martin. "Expanded Solubility Parameter Approach I: Naphthalene and Benzoic Acid in Individual Solvents." Journal of Pharmaceutical Sciences. Volume 73, number 2, page 179-188, 1984.

Solute = Benzoic Acid

Solubility at 25°C

Solvent Pyridine Dimethyl sulfoxide N,N-Dimethylformamide N,N-Dimethylacetamide N-Methylformamide

wt % 64.0 61.9 61.7 60.7 51.9

Could solvent blends give higher solubility?

Solubility > 50.0 wt%

2000-11-15-01

Design Steps







2000-11-15-01



Solute + 1,1,1-Trichloroethane + 1,2-Dichloroethane Solute + 1,1,1-Trichloroethane + 1,2-Propylene glycol Solute + 1,1,1-Trichloroethane + 1,4-Dioxane Solute + 1,1,1-Trichloroethane + 1-Butanol ● ● ● ● Solute + Water + n-Octane Solute + Water + n-Pentane Solute + Water + o-Xylene Solute + Water + p-Xylene

62 Common Solvents Generate all Combinations

1,891 Binary Solvent Blends

2000-11-15-01



10.0 20.0 30.0 . . .

Solute 22.5 20.0 17.5 . . .

Solvent1 67.5 60.0 52.5 . . .

Solvent2

10.0 20.0 30.0 . . .

67.5 60.0 52.5 . . .

22.5 20.0 17.5 . . .

34,596 compositions

1 : 3 Solvent Ratio

3 : 1 Solvent Ratio

2000-11-15-01

Design Steps







2000-11-15-01

Benzoic Acid, wt%0.0 5.0 10.0 15.0 20.0 25.0 30.0 35.0 40.0

Tem

pera

ture

, °C

-5.0

4.4

13.8

23.1

32.5

41.9

51.3

60.6

70.0



Data from: Thati, Nordström and Rasmuson. Journal of Chemical and Engineering Data. Volume 55, number 11, page 5124-5127, 2010.

−

∆−=+

m

fus

TTRH

x 11lnln γ

UNIFAC VLE Data Values

Benzoic acid + Chloroform

2000-11-15-01



Candidate Binary Blends Solvent 1 Ethanol Ethylene glycol 2-Butanone Acetone

Solvent 2 Methanol Methyl acetate 2-Propanol Butyl acetate

wt % 15.0 54.4 54.7 54.7

wt % 45.0 18.1 18.3 18.3

BA wt % 40.0 27.5 27.0 27.0

Acetone (32.41 wt%) Butyl acetate (17.7 wt%) BA Solubility in Pure Solvents

2000-11-15-01

Designing an Anti-icing Fluid


Aircraft Wing

2000-11-15-01

Design Steps







2000-11-15-01

Anti-icing Fluid Design

Biological Oxygen Demand Freezing Point Depression Viscous Shear Thinning Aquatic Toxicity Flammability Corrosivity Wettability Color


Anti-icing Fluid Aircraft Wing

2000-11-15-01

Design Steps







2000-11-15-01


Freezing Point Depressants: 419 Corrosion Inhibitors: 17 Surfactants: 19 Thickeners: 5 Antifoams: 2 Dyes: 1 Water


Aircraft Anti-icing Fluid (after preliminary screening)

(generate independent sub-formulations)

2000-11-15-01

Design Steps







2000-11-15-01




Anti-icing Fluid Aircraft Wing

2000-11-15-01



−

∆−=+

m

fus

TTRH

x 11lnln γ

Tem

p, °C

Weight %

Liquid

Solid

Assume a Simple Eutectic Property Model

Need γ, ∆Hfus, Tm

for each candidate

Estimate Freezing Point Depression

2000-11-15-01


Le Chatelier’s Method


∑=

i

imix

LFLyLFL 1

∑= imix yLFL

)( fvp

iiii TPxy γ=

VLE Calculation

300

325

350

375

400

425

450

475

500

0.0 0.2 0.4 0.6 0.8 1.0

Data ValuesEstimates

Wt frac Squalane

Flas

h Po

int [

K]

Decane - Squalane Estimate Mixture Flash Points

2000-11-15-01

ACRP 02-01


DEG without Antifoam DEG with Antifoam

Formulation remained on surface for more than 30 minutes without draining

2000-11-15-01



Niagara Falls, February 2006

2000-11-15-01




Anti-icing Fluid

Aircraft Wing

Final Formulation 1. Diethylene glycol 2. Tergitol® TMN-10 3. Triethanolamine 4. Carbopol® 1610 5. Shilling Green 6. Water

2000-11-15-01

How is it Done?







2000-11-15-01

Questions?

Michael Hill [email protected]

www.cheme.columbia.edu/michael-i-hill

Kevin G. Joback [email protected] www.molecularknowledge.com


mailto:[email protected]

http://www.cheme.columbia.edu/michael-i-hill

mailto:[email protected]

http://www.molecularknowledge.com/

chemical product design how is it done?...2000-11-15-01 how is it done? molecular knowledge systems,...

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