Phase equilibrium studies on N-oxidation

systems to identify inherently safer

operating conditions

Sunder Janardanan

Mary Kay O’ Connor Process Safety Center

Chemical Engineering Department,

Texas A&M University,

College Station, TX

4/28/2016

Sunder Janardanan

Born in Mumbai, India

B. Ch. E., Chemical Engineering (2008 - 2012),

Institute of Chemical Technology ( Formerly U.D.C.T),

Mumbai, India

Ph.D., Chemical Engineering (2012 - present),

Mary Kay O’Connor Process Safety Center,

Artie McFerrin Department of Chemical Engineering

Texas A&M University,

College Station, USA

2

Inherent Safety

Four major principles

3

New concepts Description

Ensure Dynamic Stability Design processes with wider operating limits

Limit Hazardous Effects Increase separation distance between units

Hybridization Make reactions inherently safer by adding inert

chemicals

E.g. Addition of water to cyclohexane renders the

vapor mixture inflammable during oxidation

(Chen et al. , (2004))[47]

Minimization Substitution Moderation Simplification

Use lower

quantities of

hazardous

chemicals

Replace

hazardous

chemicals with

safer ones

Operate at

conditions

which are less

hazardous

Reduce design

complexities to

reduce operator

errors

Introduction: N-oxidation of alkylpyridines

Commonly used in pharmaceutical industries

Current industrial practices:

Catalyst used : Phosphotungstic acid hydrate (PTA)

Reaction temperature : 85-100 οC

Decomposition reaction [6]:

2H2O2 2H2O + O2

o Rate is affected by temperature and presence of impurities

o Reduces the overall safety of the process

2,6-dimethylpyridine

(2,6-lutidine)

2,6-dimethylpyridine N-oxide

(2,6-lutidine-N-oxide)

+ H2O2 ------> + H2O

(30%)

PTA

ΔHdec = -98.3 kJ/mole

4

Previous incidents due to

peroxide decomposition

Rocky Flats Inc., Colorado (1957)[7]

Hydrogen peroxide was used to precipitate plutonium from

nitric acid solution

Feed solution contained impurities like iron, copper, chromium

and nickel

Sudden increase in pressure due to uncontrolled addition of

50% H2O2 solution leading to an explosion

Elf Atochem North America Inc., Minnesota (1997)[9]

Hydrogen peroxide was used to epoxidize vegetable oil

Incompatible material entered the fluid transfer line containing

a mixture of acetic acid, hydrogen peroxide and water leading

to an explosion

5

Previous work on N-oxidation

Kinetic models for the N-oxidation reaction [6,17-21, 26]

Effect of catalyst and temperature on the reaction

Increasing the catalyst concentration favored the N-oxidation

Operating the reaction at 110 -125 οC reduces the peroxide

decomposition in case of methylpyridine N-oxidation

Effect of aqueous - organic phase separation during the reaction:

Dimethylpyridines are immiscible in the aqueous phase leading to

formation of two phases

Peroxide decomposition was significant during dimethylpyridine N-

oxidation

However, product N-oxide increases the miscibility of

dimethylpyridine in the aqueous phase

Phase equilibrium studies can identify the region of homogeneity

6

Objective: To study the phase equilibrium of aqueous solutions

of 2,6-dimethylpyridine, catalyst and 2,6-dimethylpyridine N-

oxide

Motivation: Adding product N-oxide to initial reactant mixture

to ensure homogeneity during N-oxidation reactions - an

example of Hybridization

7

Research Highlights

FTIR

RC1e Calorimeter

Phase equilibrium study

System components

2,6-dimethylpyridine (DMP)

2,6-dimethylpyridine N-oxide (N-oxide)

Water

Phosphotungstic acid (PTA)

Various types of equilibrium

8

S-L-L-V S-L-V L-L-V L-V

A A

O O

V V V V

L L

PTA

V – Vapor

O – Organic

A – Aqueous

Research plan

Effect of N-oxide on DMP-Water phase separation:

Mixtures containing known concentrations of DMP and

N-oxide were heated to the desired temperature

Step-wise addition of water to this system

System was allowed to equilibrate

after each addition

FTIR probe was used

to collect the absorption spectrum

Difference in the spectrum of a

two phase system from a

single phase system was used

to determine phase separation

DMP + N-oxide

Water

DMP + N-oxide +Water

9

Mettler Toledo’s RC1e Reaction Calorimeter

10

11

DMP and N-oxide

mixture

Water

Research procedure

Effect of N-oxide on DMP-Water phase separation at 110 οC

12

RC1e Results

Component Concentration

(w/w %)

DMP 80

N-oxide 20

Step DMP

(w/w %)

N-oxide

(w/w %)

Water

(w/w %)

1 74.15 18.43 7.42

2 69.03 17.16 13.81

3 64.57 16.05 19.38

4 60.65 15.08 24.27

5 57.18 14.22 28.60

6 54.09 13.45 32.47

7 51.31 12.76 35.93

8 48.80 12.13 39.06

Component Concentration

(w/w %)

DMP 60

N-oxide 40

Step DMP

(w/w%)

N-oxide

(w/w%)

Water

(w/w%)

1 55.64 36.97 7.39

2 51.81 34.42 13.76

3 48.48 32.21 19.32

4 45.54 30.26 24.20

5 42.95 28.53 28.52

6 40.63 26.99 32.38

7 38.55 25.61 35.84

15 16.31 10.84 72.85

20g -

Water

Preliminary results

Component Concentration

(w/w %)

DMP 85

N-oxide 15

Step DMP

(w/w %)

N-oxide

(w/w %)

Water

(w/w %)

1 78.57 13.87 7.40

5 60.64 10.70 28.53

6 58.95 10.40 30.52

7 57.36 10.12 32.39

Component Concentration

(w/w %)

DMP 75

N-oxide 25

Step DMP

(w/w %)

N-oxide

(w/w %)

Water

(w/w %)

1 66.55 22.40 11.05

2 59.93 20.17 19.90

3 54.51 18.35 27.15

4 49.99 16.82 33.19

5 47.99 16.15 35.85

6 46.16 15.53 38.31

7 44.45 14.96 40.59

8 42.87 14.43 42.70

9 41.54 13.98 44.83

10 40.16 13.52 46.67

13

Component Concentration

(w/w %)

DMP 90

N-oxide 10

Step DMP

(w/w %)

N-oxide

(w/w %)

Water

(w/w %)

1 86.31 9.85 3.84

5 72.42 8.27 19.31

6 68.04 7.77 24.19

7 64.16 7.33 28.51

Analytical tool – Fourier Transform

Infrared Spectroscopy

Interaction of infrared radiations with chemical moieties

leads to absorption

Absorption spectrum of a molecule consists of

characteristic peaks

Benefits of an ATR-FTIR system

Analysis of multicomponent mixtures

In-situ analysis

Surface measurements

Study the solubility of paracetamol in aqueous solutions

in batch crystallization units [34]

14

Mettler toledo’s ATR-FTIR

Single phase system

Two phase system

15

16

DMP-Water-N-oxide ternary plot

Temp – 110 oC

0.00 0.25 0.50 0.75 1.00

0.00

0.25

0.50

0.75

1.000.00

0.25

0.50

0.75

1.00

N-oxide (w/w)

Dimethylpyridine (DMP)

(w/w)

Water

(w/w)

Homogeneous

Heterogeneous

Binodal curve 75-25

80-20

85-25

90-10

Thermodynamic Models

Equilibrium conditions for a heterogeneous closed system [39]

T1 = T2 = T3 =……..=Tm

P1 = P2 = P3 =……..=Pm

fi1 = fi

2 = fi3 =……… =fi

m

Current System:

Components: DMP, N-oxide, Water

Two liquid phases and one vapor phase

Liquid - Liquid Equilibrium

Vapor - Liquid Equilibrium

17

xiIg IiiPi

sat = yiP = x IIi g iIIPi

sat

xiIg Iii = x

II

i g iII

m – phases,

i – components

g i - Activity coefficeint of species i

Pisat -Vapour pressure of pure species i

x, y - Liquid /Vapor mole fractions

UNIQUAC Activity Coefficient Model

Activity coefficient (γi) accounts for the deviations from

ideal behavior in a mixture

It arises due to the interaction between unlike pairs of

molecules in a mixture

Universal QuasiChemical Model (UNIQUAC) of

Abrams and Prausnitz[39]:

18

lng i = lng i (combinatorial)+ lng i (residual)

lng i (combinatorial) = lnfixi

-z

2qi ln

fiqi

+ li -fixi

x jl jj

å

lng i (residual) = qi 1- ln q jt ji

j

åæ

èçç

ö

ø÷÷-

q jt ij

qkt kjk

åj

å

é

ë

êêêê

ù

û

úúúú

UNIQUAC Activity Coefficient Model

19

where li = (ri - qi )z

2- (ri -1)

z = Average coordination number

ri = volume parameter for species i

qi = Surface area parameter for species i

qi = Area fraction =xiqi

x jq jj

å

fi =Volume fraction =xiri

x jrjj

å

Volume (Ri) and Surface

area (Qi) parameters for

various functional groups

are available

lnt ij = -(uij -u jj )

RT

uij - average interaction energy for i- j

u jj - average interaction energy for j - j

(τ12 and τ12) Two adjustable

parameters for each binary

pair

Determined by regression

of experimental data

Estimation of interaction energies

through computational chemistry

Sum and Sandler studied the phase behavior for many binary systems

(methanol+water, ethanol+water, acetic acid + water)

Average interaction energies were estimated using ab intio quantum

mechanics and used in activity coefficient models (UNIQUAC and

Wilson)

20

Figure 1: Phase diagram for methanol and water at T = 323.15 oK[43]

Computational Chemistry - Overview

Computational chemistry

Molecular Mechanics

Electronic Structure Methods

Semi-Empirical

Ab initio

Density Functional

Theory

21

Basic types of calculations involve[1] –

Computing energy of a particular molecular structure or a group of

molecules

Optimizing the structure of a molecular cluster or a single molecule

(Geometric optimization)

Estimating the vibrational frequencies of molecules resulting from

interatomic motion within the molecule

Electronic Structure Methods

Time independent Schrodinger equation

Solutions to the equation corresponds to different stationary

states (Ψ) of the system

Models are classified based on the various mathematical

approximations applied to the Schrodinger's equation

Theoretical Models/Level of Theory : HF, MP2, B3LYP

Basis set - Mathematical description of molecular orbitals within

a system (3-21G, 6-31G(d), 6-31+G(d,p) 6-311G(d))

Gaussian 09 software

22

HY =EY

Y -Wavefunction Function of the positions of the electrons and

the nuclei within the molecule

Computational Procedure

Step 1 – Construction of a molecular cluster that

represents the desired system

Compromise between computational cost and a reasonable

representation of the fluid

Calculated interaction energies should be independent of the

starting geometry

Step 2 – Geometric optimization of the cluster

Selection of a theoretical method and a basis set:

Step 3 – Selection of directly interacting molecular pairs

(like and unlike) from this optimized cluster

Decision is based on the separation distances and relative

orientations of the various molecules in the cluster

23

Step 4 – Compute the energy of each molecular pair

Interaction energy is given by the following formula:

Step 5 – Linearly average the the energies of the molecular

pairs to obtain the interaction parameters in the activity

coefficient models

Procedure will be repeated for multiple initial geometries to

get consistent results

Computational Procedure

E1-2

int = E1-2 -E1 -E2

24

Preliminary Results

RN..H

10 molecule cluster

Hartree Fock (HF),

6-31G(d)

25

DMP-DMP Water-Water DMP-Water

Dimer clusters

Future Work

Using activity coefficient models to construct the phase

diagram (UNIQUAC, Wilson)

Selection of appropriate theoretical model and basis set

Study the effect of temperature and catalyst on the N-oxide-

DMP-Water phase behavior

Preliminary study on N-oxide-Water-Catalyst mixtures

suggested that N-oxide could dissolve the catalyst

Implementation of the ISD concept – Hybridization:

Reduction in peroxide decomposition due to addition of

product N-oxide to the initial reactant mixture

26

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Acknowledgements

Dr. M. Sam Mannan

Committee members

Dr. James Holste

Dr. Benjamin Wilhite

Dr. Debjyoti Banerjee

Dr. Kenneth Hall

Dr. Lisa Perez

Dr. Samina Rahmani

Dr. Maria Papadaki

Dr. Simon Waldram

Dr. Alba Pineda

Members of the Steering Committee

Members of the MKOPSC

30

31

Thank You

Questions and Comments