7 ir interpretatio njntu pharmacy

1

1

BYDr. Suman PattanayakAssociate ProfessorDepartment of Pharma Analysis & QA.

Vijaya Institute of Pharmaceutical Sciences for Women

M. Pharm/ I SemAdvance Pharmaceutical Analysis

The challenging scenario in the aspects of efficacy, safety, purity, and quality determination of the drug samples became optimistic.

Drug1 Natural ---animal ---- plants ----marine

Synthetic ----organic ----in-organic

Chemical / functionalGroup interaction2

Signal transduction1

Therapeutic effects1

Molecular basis2

sources1

Importance of analysis of drugs

Analysis basis

Drug –receptor interaction1

21.B Sue Brizuela,Ms, Judith A Hesp, MS, “Drug Information” Remington: The science and practice of pharmacy,19th edition,volume.1, Mack publishing company Easton, Pennsylvania18042, 1995. print.

2. B.K. SHARMA," fundamental principles of spectroscopy” ,spectroscopy ,20th edition, Goel publications, Delhi, 2007. print.

Ana lysis

Structure. breakdown ANALYSIS

1.Separation techniques 2.Spectrophotometric 3. Electro analytical 4. Titrimetric analysis

chromatography Potential & conductometry Titrations

1.uv-visible

2.Infra red3.Mass

4.Neclear magnetic resonance

Classification of analytical techniques3

3

3. Douglas A.Skoog, F.James Holler, Timothy A.Nieman, ,”introduction to instrumental methods of analysis", principles of instrumental analysis, 5th edition, saunders Golden sunburst series. Forth worth, Philadelohia, Chicago, Sydney, Toronto. Reprint. 2005. Print.

3

Spectroscopy[2,4,5]

EMR ANALYTE SPECTROPHOTOGRAPH

Conc. should be lower 1.UV-Visible radiations---excitation of electrons----uv-visiblespectrum

2.IR-radiations—vibration changes in electrons---IR spectrum

3.Microwave radiations---spin resonance----E.S.R spectrum

4.Radio frequency---spin rotational changes---N.M.R spectrum

study of interaction of electromagnetic radiation with matter

4. www.answers.com. Web. 25 feb 2010. http://www.answers.com/topic/spectroscopy

5. www. en.wikipedia.org. Web. 25 feb 2010 < http://en.wikipedia.org/wiki/Infrared_spectroscopy>.

2. B.K. SHARMA," fundamental principles of spectroscopy” ,spectroscopy ,20th edition, page noS-11, Goel publications, Delhi, 2007. print.

4

Principle of spectroscopy[2,4,5]

http://www.answers.com/

http://www.answers.com/topic/spectroscopy

http://en.wikipedia.org/wiki/Infrared_spectroscopy


Gamma rays

X rays

UV

Visible

Infra-Red Micro waves

Radio waves

Violet

indigo

Blue

Green

Orange

Yellow

Red

370

nm

nm

650

590

550

490

450

430

EMR Drug

substance

EnergyKcal/mol

9.4 x 107

9.4 x101

9.4 x103

9.4 x 10-1

9.4 x 10-3

9.4 x 10-5

9.4 x 10-7

Λ 0A

Frequency

(Hz)Absorbing radiations

Type

of spectroscopy

1

7 6 0 0

6 x 106

3 x 109

3 x 1013

15 0

3 8 0 0

1021

1017

1015

1013

1011

1009

1007

Emission

Both E & Abs

NMR Abs

Absorption

Absorption

Absorption

Absorption

THE ELECTROMAGNETIC THE ELECTROMAGNETIC SPECTRUMSPECTRUM

Characteristics of radiations

Resulting spectrum

5. www. en.wikipedia.org. Web. 25 feb 2010 < http://en.wikipedia.org/wiki/Infraredspectroscopy>. 2. B.K. SHARMA," fundamental principles of spectroscopy” Spectroscopy 20th edition, page no.S-11- S-20, goel publications, Delhi, 2007.print.

5

[2,5]


http://en.wikipedia.org/wiki/Infraredspectroscopy

IR -SPECTROSCOPY 2 Theory origin of spectra

Physics3

Principle observed changes

Chemistry2

Instrumentation working

Engineering6

Applications[2,3,6]

uses

pharmacy

BIO-technology

Genetic engineering

Multidisciplinary of IR spectroscopy[2,3,6]

6

2. B.K. SHARMA," Infrared spectroscopy” Spectroscopy 20th edition, page no.S-220, goel publications, Delhi, 2007.print.

3. Douglas A.Skoog, F.James Holler, Timothy A.Nieman, ,”Infrared spectroscopy", principles of instrumental analysis, 5th edition, saunders Golden sunburst series. Forth worth, Philadelohia, Chicago, Sydney, Toronto. Page no. 406. Print.

6. Hobart H. Willard, Lynne L. Merritt. Jr., John A. Dean, Frank A. Settle, Jr. “Infrared spectroscopy”, instrumental methods of analysis,7thedition page288,289,292,293, content no. 11.1 . CBS publications, Toronto. 2005. print.

REGION WAVE LENGTH

λ (μm)

WAVE NUMBER υ (cm-1)

FREQUENCY RANGE

Hz

NEAR 0.78 - 2.5 12800 - 4000 3.8x1014-1.2x1014

MIDDLE 2.5 - 50 4000 - 200 1.2x1014 - 6x112

FAR 50 - 1000 200 -10 6x1012- 30x1011

MOST USED 2.5 - 15 4000 - 670 1.2x1014-2x1013

IR-REGION: 12,800 - 10 cm-1

1.Near IR----carbohydrates and proteins2.Middle IR-----organic molecules—functional groups

3.Far IR—in-organic –co-ordination bonds& quaternary ammonium compounds

3. Douglas A.Skoog, F.James Holler, Timothy A.Nieman, ,”Infrared spectroscopy”, introduction to instrumental methods of analysis", principles of instrumental analysis, 5 th edition, saunders Golden sunburst series. Forth worth, Philadelohia, Chicago, Sydney, Toronto. Page no. 406. Print.

6. Hobart H. Willard, Lynne L. Merritt. Jr., John A. Dean, Frank A. Settle, Jr. “Infrared spectroscopy”, instrumental methods of analysis,7thedition page288,289,292,293, content no. 11.1 . CBS publications, Toronto. 2005. print.

[3,6]

7

REGION Detectors Source of radiation

Optical system

Type of samples

NEAR Photo conductance

Tungsten filament lamp

Prism grating

Solid / liquid

MIDDLE Thermal type Nernst glowers/ Nichrome wire

Diffraction grating

Liquid / gas

FAR Golay, pyroelectric

High pressure mercury lamp

Double beam grating

Gas

MOST USED

Thermal type Nernst glowers/ Nichrome wire

Diffraction grating

Liquid / gas

Type of analysis

measurement

Qualitative Quantitative

Diffusive reflectance Absorption

Qualitative Quantitative Chromatographic

Diffusive reflectanceAbsorptionAdsorption

Quantitative emission

Qualitative Quantitative Chromatographic

Diffusive reflectanceAbsorptionAdsorption

INSTRUMENTAL AND APPLICATIONS OF VARIOUS IR REGIONS[7,8]

7. www. orgchem.colorado.edu. web,.25.2010. < http://orgchem.colorado.edu/hndbksupport/irtutor/tutorial.html >

8.Donald L.Pavia, Gary M.Lampman, George S. Kriz.”infrared spectroscopy "introduction to spectroscopy,3rd edition, CBSPublications Thomas books Australia,

U.S.print ,Canada, Mexico, 2007. print..8

http://orgchem.colorado.edu/hndbksupport/irtutor/tutorial.html

Due to 4 changes in energies of the molecules1. Electronic transitions -----E t

2. Electronic rotations -------E r

3. Electronic vibrations-------E v

4. Electronic energy-----------E e total energy of the molecule= E e + E v + E r + E t

energies required in the order ----- E e > E v> E r > E t

Various types IR –spectra1. Rotational spectra2. Vibrational- rotational spectra3. Electronic band spectra

ORIGIN OF IR SPECTRUM [2,3]

2. B.K. SHARMA," Infrared spectroscopy” ,spectroscopy ,20th edition, Goel publications, Delhi, 2007. print. 3. Douglas A.Skoog, F.James Holler, Timothy A.Nieman,”Infrared spectroscopy”, introduction to instrumental methods of analysis", principles of

instrumental analysis, 5th edition, saunders Golden sunburst series. Forth worth, Philadelohia, Chicago, Sydney, Toronto. Page no. 406. Print. 9

Differences between various types of IR spectra2,(a,b,c)

Character Electronic band spectra a

Vibration- rotational spectra b

Rotational spectra c

1. IR region Near IR Middle IR Far IR

2.Energy required Higher less very less

3.Dipole moment less induced Definite dipole Intense dipole

4.Sample state Solids Liquids / gases

Only gases

5.Thoery supporting Frank codon principle

Harmonic oscillator principle

Rigid rotor principle

6.Changes observed Excitation, vibration

Vibration , rotation Only rotation

7.Highly feasible for single bonds double bonds Triple bonds

2. B.K. SHARMA," Infrared spectroscopy” ,spectroscopy ,20th edition, Goel publications, Delhi, 2007. print.

a.S-234 to s-249 b. s-220 to s- 234 c. s-201 to s-220. 10

1. Selection rules9

2. Types of vibrations9

3. Number of possible vibrational modes10

4. Vibrational frequency[9,10]

5. Factors influencing vibrational modes[9,10]

INFRARED THEORY [9,10]Matching of Frequency

Dipole moment

Vibrational Quantum Number

Translational motion

Rotational motion

Vibrational motion

A. Phase and solvents used

B. Coupled interactions

C. Hydrogen bonding

D. Fermi resonance

E. Electronic effects9. Robert M.Silverstien Francis X.Webster ,”infrared spectroscopy”, spectroscopic identification of organic compounds, 6thedition, John Wiley, Chichester, Singapore, Toronto, Brisbane page no. 3.5, 2005. Print.10. Jag Mohan ,”infrared spectroscopy”, Organic Spectroscopy, Principles And Applications, 2ndedition,Narosa,Newdelhi, Chennai 2005. Print.

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Asymmetric (nu) Symmetric (nu) Scissoring (s) Rocking (ρ )Wagging (ω)Twisting (tau)

Stretching vibrations Bending vibrations

In-plane Out -plane

2925 2850 1465 1350 1150 720 cm-1

In-plane

Types of vibrations [5,11]

Vibrational energy depends on :- 1. masses of the atoms 2. strength of bonds

3. arrangement of atoms within the molecule5. www. en.wikipedia.org. web.25 feb 2010. < http://en.wikipedia.org/wiki/Infrared_spectroscopy>.11. Dudles H,Williams,Ian Fleming ,”infrared spectroscopy”, Spectroscopy Methods In Organic Chemistry, 5thedition,Tata mecGrawHill.Education. Newyork, Singapore, Sydney, 2004. Print. 12

For stretching vibration = N -1For bending vibration [(3N - 6)-(N -1)]=2N -5 for non-linear [(3N - 5)-(N -1)] =2N – 4 for linear ‘N’ is the number of atoms in the bond.

http://upload.wikimedia.org/wikipedia/commons/0/0e/Symmetrical_stretching.gif

http://en.wikipedia.org/wiki/Image:Asymmetrical_stretching.gif

http://en.wikipedia.org/wiki/Image:Scissoring.gif

M1 Force constant, k M2

Ball and spring representation of 2 atom of molecule vibrating in the direction of bond

Vibrational frequency2

Factors influencing absorption frequency2

Masses of attached atoms. As masses increase, wave number decreases.

Strength of chemical bond. As bond strength increases, wave number increases.

Hybridization. Bonds are stronger in the order sp > sp2 > sp3.

Resonance. Conjugation lowers the energy to vibrate bond.

2. B.K. SHARMA," Infrared spectroscopy” ,spectroscopy ,20th edition, Goel publications, Delhi, 2007. print.13

A. Phase and solvents usedPhase and solvents may bring the changes in IR in the aspects of1.Band frequency shifts

2. Band splitting e.g.;- the effect of phase and solvents in Acetone. >c=o in acetone ----------1742 cmcm-1 -1 in vapor statein vapor state -----------1718 cm -----------1718 cm-1-1 in liquid state in liquid state

Acetone interactions with some solvents Acetone interactions with some solvents -----------1726 cm -----------1726 cm-1-1 in a solution of Hexane in a solution of Hexane -------------1713 cm -------------1713 cm-1-1 in chloroform in chloroform --------------1709 cm--------------1709 cm-1-1 in ethanol in ethanol

Dipole-dipole lowers wave number

Factors influencing vibrational modes [2,10,12]

2. B.K. SHARMA," Infrared spectroscopy” ,spectroscopy ,20th edition, Goel publications, Delhi, 2007. print. 10. Jag Mohan ,”infrared spectroscopy”, Organic Spectroscopy, Principles And Applications, 2ndedition,Narosa,Newdelhi, Chennai 2005. Print. 12.Y.R.Sharma,”infrared spectroscopy”, Elementary organic spectroscopy principles and chemical applications, first edition 1980, reprint 2007. print.

14

B. Coupled interactions Extent of coupling influenced by 1.stretching vibrations with two vibrations have common atom 2. bending vibrations with a common bond b/t vibrating groups. 3. coupled groups of identical energies. 4. groups separated by two/more bonds, little or no interaction occur. 6. vibrations of symmetrical species.

Factors influencing vibrational modes[2,10,12]


15

Strength of H-bond effected by 1. ring strain 2. molecular geometry 3. relative acidity and basicity of proton donor and acceptor

C.. Hydrogen bonding

Types of hydrogen bonding :- 1. intermolecular hydrogen bonding extent of bonding depends on Temp. 2. intramolecular hydrogen bonding

D. Fermi resonance Factors leads to Fermi resonance a) vibrational levels are same for symmetrical compounds. b) interacting groups located in the molecule for an appreciable mechanical coupling to

occur.e.g.:- 1. co2 actual absorption frequencies at 1286,1388 cm-1 the splitting caused by coupling b/t cm-1 the splitting caused by coupling b/t

fundamental c=o stre. near 1340 cmfundamental c=o stre. near 1340 cm-1-1 and 667 cm and 667 cm-1-1 -----1344 cm -----1344 cm-1-1 1 1stst overtone overtone 2. lactones, lactims, lactums, aldehydes.

Factors influencing vibrational modes [2,10,12]

1.Inductive effect—introduction of alkyl group length

2.Mesomeric effect bond strength

3.Field effect. force constant vibrational frequency

E. Electronic effects

► Lone pair of electrons► conjugation lowers absorption► Mesomeric effect dominate inductive effect for some time and vice versa

Introduction of electronegative atoms Bond strength Force constant

Vibrational frequency

HCHO----1750 cm-1cm-1

CH3CHO---1745 cm-1cm-1

CH3COCH3---1715 cm-1cm-1

CH3COCH3---1715 cm-1cm-1

ClCH2COCH3---1725 cm-1cm-1

Cl2CHCOCH3----1740 cm-1cm-1


INSTRUMENTATION [2,6]

1.Radiation source

2. Monochromatic light.

3.Sample handling.

4.Detectros

5.Amplifiers .

2. B.K. SHARMA," Infrared spectroscopy” ,spectroscopy ,20th edition, Goel publications, Delhi, 2007. print. 6. Hobart H. Willard, Lynne L. Merritt. Jr., John A. Dean, Frank A. Settle, Jr. “Infrared spectroscopy”, instrumental methods of analysis,7thedition content no. 6.18. CBS publications, Toronto. 2005. print.

17

2.Sampling of substances

solids

liquids

gases .

1.solids run in solution form2.solid films3.mull technique4.pressured pellet technique.

S.NO Character Nernst glower

Globar Incandescent Mercury arc

Tungsten lamp

Co2 laser

1. Composition Rare earth oxides

Silicone carbide

Nichrome wire High (Hg) pressure

Tungsten – Halogen

Tunable Co2 laser.

2. Operating temp.

1200 —2200K

1300 ---1500 K

1100K 1000K 3500K -------

3. Radiations produced O.P

12,800-4000cm-1cm-1

5200 cm-1cm-1 10,800--8000cm-1cm-1

< 665 cm-1cm-1 10,100—4000 cm-1cm-1

1100-900cm-1cm-1

4. IR region used Near / visible Middle Near Far Middle Middle /near

5. Intensity of radiation

More intense As equal to Nernst

Less but longer life.

Greater Mild More effective

6. Out put significant (λ)

>2µm >5µm 2-4µm 10µm 2-4µm 5 µm

7. Used for Carbohydrate , protein

Simple Functional groups

complex organic molecules.

In- organic complexes.

Most organic functional groups

NH3 C6H6, C2H5OH

INFRARED SOURCES [3,6]

3.Douglas A.Skoog, F.James Holler, Timothy A.Nieman, ,”Infrared spectroscopy", principles of instrumental analysis, 5th edition, saunders Golden sunburst series. Forth worth, Philadelohia, Chicago, Sydney, Toronto. Page no. 406. Print.6. Hobart H. Willard, Lynne L. Merritt. Jr., John A. Dean, Frank A. Settle, Jr. “Infrared spectroscopy”, instrumental methods of analysis,7thedition page288,289,292,293, content no. 11.1 . CBS publications, Toronto. 2005. print.

18

S.No Character

Thermocouple orThermopile

Thermister or Bolometer

Pyroelectric Golay or Pneumatic

1. Principle Pelletier effect Whetstone bridge Electric polarization

Expanction of gases

2. Materials used Bismuth & Antimony, coated by metal oxides

Sintered oxides of Mn, co, Ni

TGS, DTGS, LiTGO3 , LiTubO3

generally CO2

3. Material should be Thermally active Thermally sensitive resistors

Non-center symmetric crystal

Inert nature

4. Description Half -junction- hotAlternate -junction -cold

-------------- ------------ Metal cylinder closed in b/t metal plate & Ag

5. Conversion unit Radiant to Electric signal ---measured

Change in resistance - Q

Thermal alteration to E.polarization

Expanction of gas to pressure to e.signal

6. Used Photocuastic spectroscopy

Diffusive reflectance

FTIR Non –dispersive IR

7. Response time 30 sec 4 sec multiple scanning 0.01sec

DETECTORS or TRANSDUCERS[3,6]

3.Douglas A.Skoog, F.James Holler, Timothy A.Nieman, “ Infrared spectroscopy”, introduction to instrumental methods of analysis, principles of instrumental analysis, 5th edition, saunders Golden sunburst series. Forth worth, Philadelohia, Chicago, Sydney, Toronto. Page no. 408-410. 2006 Print.6. Hobart H. Willard, Lynne L. Merritt. Jr., John A. Dean, Frank A. Settle, Jr. “Infrared spectroscopy”, instrumental methods of analysis,7thedition page288,289,292,293, content no. 11.1 . CBS publications, Toronto. 2005. print.

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► 3600—3000cm-1

---OH, --NH2 , >NH, C-H.C-H.

► 3200—3000cm-1

C-H, Ar— C-H.C-H, Ar— C-H.

►3000—2500 cm-1

--C—H of methyl/methelene

asymmetric stre. --C—H, --COOH

►2300—2100 cm-1

Alkynes 2210---2100

Cyanides 2260—2200

Isocyanides 2280—2250

►1900—1650 cm-1

strong bands--- >c=o---1725—1760

anhydrides ----- 1850---1740

Imides ------ two broad band at 1700

Functional [11,13] group region

11.Dudles H,Williams,Ian Flemming ,”infrared spectroscopy”, Spectroscopy Methods In Organic Chemistry, 5thedition,Tata mecGrawHill.Education. Newyork, Singapore, Sydney, page no. 45-60. 2004 . Print.13.Harold F.Walton,Jorge Reyes, "infrared spectroscopy", Modern Chemical Analysis And Instrumentation,IMBD, Mumbai, Reprint 2001page no 201-203. Print.

20

General guidelines for IR [11,13]

► 1650--1000cm-1

confirms --- esters, alcohol, ethers. Nitro

► 1000—800 cm-1 C— Cl, C-Br

► 800—710cm-1

meta substituted benzene

► 770—730cm-1

strong mono substituted benzene.

► 710—665cm-1

ortho, Para, benzene.

Finger print region[11,13]

11.Dudles H,Williams,Ian Flemming ,”infrared spectroscopy”, Spectroscopy Methods In Organic Chemistry, 5thedition,Tata mecGrawHill.Education. Newyork, Singapore, Sydney, page no. 45-60. 2004 . Print.13.Harold F.Walton,Jorge Reyes, "infrared spectroscopy", Modern Chemical Analysis And Instrumentation,IMBD, Mumbai, Reprint 2001page no 201-203. Print.

21

General guidelines for IR interpretation [11,13]

O—H N—H

C—H C—C HO-C=O C=_N C=O C=N C=C C=S N=O S=O C—N C—O benzene

%T

Graphical interpretation of functional groups in IR [2,10]

222. B.K. SHARMA," Infrared spectroscopy” ,spectroscopy ,20th edition, Goel publications, Delhi, 2007. print. 10. Jag Mohan ,”infrared spectroscopy”, Organic Spectroscopy, Principles And Applications, 2ndedition,Narosa,Newdelhi, Chennai 2005. Print.

OH, --NH2 , >NH, C-HC-H

C-H, Ar— C-HC-H, Ar— C-H

C—H, --COOH

esters, alcohol, ethers, Nitro groups

Alkanes

C–H stretch from 3000–2850 cm-1

C–H bend or scissoring from 1470-1450 cm-1

C–H rock, methyl from 1370-1350 cm-1

C–H rock, methyl, seen only in long chain alkanes, from 725-720 cm-1

Wave number cm-1

90

0

C-H stretch2971 2963

4000 2000 1000 500

1470 7281383

C-H rock

C-H scissoring

Long chain CH2 stretch

Octane spectrum

10. Jag Mohan ,”infrared spectroscopy”, Organic Spectroscopy, Principles And Applications, 2ndedition,Narosa,Newdelhi, Chennai 2005. Print.

11.Dudles H,Williams,Ian Flemming ,”infrared spectroscopy”, Spectroscopy Methods In Organic Chemistry, 5thedition,Tata mecGrawHill.Education. Newyork, Singapore, Sydney, page no. 45-60. 2004 . Print.

23


Alkenes :-

C=C stretch from 1680-1640 cm-1

=C–H stretch from 3100-3000 cm-1

=C–H bend from 1000-650 cm-1

90

% tr

ansm

ittan

ce

Wave number cm-1

1 45

2 36

7

1. 3083- =C-H stretch

2. 2966- C-H stretch

3. 2863 –C-H stretch

4. 1644- C=C str

5. 1455 C-H sis

6. 1378 C-H rock

7. 1004 =C-H bond

1- Octene spectrum

4000 2000 1000 500

24

General guidelines for IR interpretation[1011]



Alkynes :-

–C≡C– stretch from 2260-2100 cm-1

–C≡C–H: C–H stretch from 3330-3270 cm-1

–C≡C–H: C–H bend from 700-610 cm-1

90

0

C-H stretch

3324

2971

4000 2000 1000 500

1470636

1383C-H rock

C-H scissoring

C-H scissoring

CCC- HC- H

CCC- C- 2126

2679

1- hexyne spectrum

% transmittance

Wavelength cm-1

25




Alkyl halides :-

C–H wag (-CH2X) from 1300-1150 cm-1

C–X stretches (general) from 850-515 cm-1

C– Cl stretch 850-550 cm-1

C–Br stretch 690-515 cm-1

90

0

C-H stretch2976 2940

4000 2000 1000 500

1470 6511291

C-H wag

C-H scissoring

Long chain, C-Br stretch

1- bromo propane spectrum

26




Aromatics:-

C–H stretch from 3100-3000 cm-1

overtones, weak, from 2000-1665 cm-1

C–C stretch (in-ring) from 1600-1585 cm-1

C–C stretch (in-ring) from 1500-1400 cm-1 C–H "loop" from 900-675 cm-1

C-H stretch aromatics

3068

% transmittance

90

0

C-H stretch alkyl2925

1614

1505

C- H stretch In aromatic ring

Wavelength cm-1

1465

3032

3099

overtones

738

10351086

In-plane C-H bending

Aromatic C-H stretches are left to 3000, and aliphatic C-H stretches are right to 3000

Spectrum of Toluene

27




Alcohol:-

O–H stretch, hydrogen bonded 3500-3200 cm-1

C–O stretch 1260-1050 cm-1 (s) The spectrum of ethanol is shown below. Note the very broad, strong band of the O–H stretch (3391) and the C–O stretches (1102, 1055).

O-H stretch

3391

Wave number cm-1

% transmittance

90

0

C-H stretch2961

1102

1105C-O stretch

Spectrum of Ethanol

28

General guidelines for IR interpretation[10,11]



ketones

C=O stretch: aliphatic ketones 1715 cm-1

α, β-unsaturated ketones 1685-1666 cm-1

The spectrum of 2-butanone is shown below. This is a saturated ketone, and the C=O band appears at 1715. Note the C–H stretches (around 2991) of alkyl groups.

C-H stretch

2991

1715 C=O stretch

Wave number cm-1

% transmittance

90

0

2-butanone spectrum

4000 3000 2000 1500 1000 500

29




Aldehydes:

H–C=O stretch 2830-2695 cm-1

C=O stretch: aliphatic Aldehydes 1740-1720 cm-1

alpha, beta-unsaturated aldehydes 1710-1685 cm-1

The spectra of benzaldehyde and butyraldehyde are shown below. Note that the O=C stretch of the alpha, beta-unsaturated compound -- benzaldehyde -- is at a lower wave number than that of the saturated butyraldehyde.

C-H

Stretch alkyl

3073

1696 C=O stretch

Wave number cm-1

% transmittance

90

0

28272725C-H aldehyde

Benzaldehyde spectrum

4000 3000 2000 1500 1000 500

30




Carboxylic acids :-

O–H stretch from 3300-2500 cm--1

C=O stretch from 1760-1690 cm-1

C–O stretch from 1320-1210 cm-1 O–H bend from 1440-1395 and 950-910 cm-1

The spectrum of hexanoic acid is shown below. Note the broad peak due to O–H stretch superimposed on the sharp band due to C–H stretch. Note the C=O stretch (1721), C–O stretch (1296), O–H bends (1419, 948), and C–O stretch (1296

O-H stretch and C-H stretch

2971

1721C=O stretch

Wave number cm-1

% transmittance

90

0

1419O-H band 1296

C-O stretch

948O-H

31




Esters :-C=O stretch

aliphatic from 1750-1735 cm-1

α, β-unsaturated from 1730-1715 cm-1

C–O stretch from 1300-1000 cm-1

The spectra of ethyl acetate and ethyl benzoate are shown below. Note that the C=O stretch of ethyl acetate (1752) is at a higher wavelength than that of the α, β-unsaturated ester ethyl benzoate (1726). Also note the C–O stretches in the region 1300-1000 cm-1

.

90

90

% tr

ansm

ittan

ce

Wave number cm-1 4000 3000 2000 1000 500

1 2 3

12 3 4

Ethyl acetate

1. 2981- C-H stretch

2. 1752- C=O ester stretch

3. 1250- C-O stretch

4. 1055- C-O stretch

4

Ethyl benzoate1. 3078- C-H aromatic

stretch

2. 2966- C-H alkyl stretch

3. 1726-C=O stretch

4. 1266, 1117- C-O stretch

32

General guidelines for IR interpretation[10,11]



Amines :-

N–H stretch 3400-3250 cm-1

1° amine: two bands from 3400-3300 and 3330-3250 cm-1

2° amine: one band from 3350-3310 cm-1

3° amine: no bands in this region

N–H bend (primary amines only) from 1650-1580 cm-1

C–N stretch (aromatic amines) from 1335-1250 cm-1

C–N stretch (aliphatic amines) from 1250–1020 cm-1

N–H wag (primary and secondary amines only) from 910-665 cm-1

33




90

90

90

% tr

ansm

ittan

ce

Wave number cm-1 4000 3000 2000 1000 500

Aniline

1.3442

2. 3360-

3. Shoulder band

4. 1619- N-H primary amine

5.1281- C-N stretch Diethyl amine

1. 3288- N-H stretch Secondary amine

2.1143- C-N stretching

3.733- N-H waging 10 ,20.

1

4 52 3

1 2 3

1

Tri ethyl amine

1. 1241- C-N stretching

10,20,30 amine spectrums

34




Nitro groups:-

N–O asymmetric stretch from 1550-1475 cm-1

N–O symmetric stretch from 1360-1290 cm-1

N-O stretch1573 1383

N-O stretch

Wave number cm-1

% transmittance

90

0N-O stretch1537

1358

Black spectrum Blue spectrumNitro methane Meta nitro toluene

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Example for interpretation of IR for known structure[9,10,14]

HN

OH

CO

CH3

Acetaminophen 14

(4-acetamido-Phenol)

A. N-H Amide----3360 cm -1 .

B. Phenolic—OH -- 3000 cm -1 --3500 cm -1

C. C—H Stretching---3000 cm-1 .

D. Aromatic overtone ----1840 cm-1 --1940 cm -1

E. >C=O Amide stretching -----1650 cm -1

F. Aromatic C=C stretching--- 1608 cm -1 .

G. N-H Amide bending ----1568 cm -1

H. Aromatic C=C stretching ----1510 cm -1 .

I. >C—H bending --------810 cm -1

A

B

C

D

E

F

G

HI

9. Robert M.Silverstien Francis X.Webster ,”infrared spectroscopy”, spectroscopic identification of organic compounds, 6thedition, John Wiley, Chichester, Singapore, Toronto, Brisbane page no. 3.5, 2005. Print.

10. Jag Mohan ,”infrared spectroscopy”, Organic Spectroscopy, Principles And Applications, 2ndedition,Narosa,Newdelhi, Chennai 2005. Print. 14.David watson,”infrared spectroscopy”, pharmaceutical Analysis, A test book for pharmacy students & pharmaceutical chemists, 2nd

edition, Elsevier churchil,livingston. Edinburgh,london,newyork,oxford,sydney, and Toronto. Print

36

C

O

H3C

15.www.cem.msu.edu. Web feb 25 2010. < http://www.cem.msu.edu/~reusch/VirtualText/Spectrpy/InfraRed/irspec1.htm#ir1 >

15

37

Examples for interpretation of IR for known structure15

15

OH

C

O

HOO

C

O

CH3

C

O

HO

15 15

Tips for interpretation of IR for unknown structure 14

Always place relines to negative information evidence i.e., absence of band at 1900 cm-1---1600 cm-1----absence of >C=O, >CHO

Always starts from higher frequency end of the spectrum.

Absence of band at 880 cm-1—650 cm-1 indicates absence of aromatic ring.

For easy identification go for fingerprint and functional group region.

Finger print region range is 1400 cm-1--900 cm-1. In this region if absorbance band is present the groups esters, alcohols, ethers, nitro are Confirmed.

Functional region range is 4000 cm-1---1400 cm-1.amines, alcohols, aromatic rings, carboxylic acids, alkynes, alkanes, alkenes, anhydrides, imides, etc, may be confirmed.

Stretching vibrations at 4000 cm-1----600 cm-1.

Bending vibrations at 1500 cm-1-----500 cm-1.

3814.David watson,”infrared spectroscopy”, pharmaceutical Analysis, A test book for pharmacy students & pharmaceutical chemists, 2nd

edition, Elsevier churchil,livingston. Edinburgh,london,newyork,oxford,sydney, and Toronto. Print

Sat’d

C=0 C=C

CH3CH2

AromaticP- Disubst

AromaticP- Disubst

Carbonyl GroupCarbon Oxygen GroupPrimary Amine GroupSaturated AlkaneUnsaturated Alkene / AromaticMethyl Group

Wave number cm-1

% transmittance

90

0

4000 3000 2000 1500 1000 500

NH2

Unsat’d

39

Example for interpretation of IR for unknown structure[14,15]


14.David watson,”infrared spectroscopy”, pharmaceutical Analysis, A test book for pharmacy students & pharmaceutical chemists, 2nd edition, Elsevier

churchil,livingston. Edinburgh,london,newyork,oxford,sydney, and Toronto. Print

3350 -- OH stetching vibrational frequency2950 -- CH aliphatic asymmetrical stretching vibrational band. The less intense band at 2860 – is the symmetrical stretching vibrational band.1425 -- CH2 characteristic absorption1065 -- CO absorption

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Example for interpretation of IR for unknown structure15


POSITION REDUCED MASS

BOND STRENGTH

(STIFFNESS)

LIGHT ATOMS HIGH

FREQUENCY

STRONG BONDS HIGH FREQUENCY

STRENGTH CHANGE IN ‘POLARITY’

STRONGLY POLAR BONDS GIVE INTENSE

BANDS

WIDTH HYDROGEN BONDING

STRONG HYDROGEN BONDING

GIVES BROAD BANDS

Peak status Reason inference

Conclusion

IR

spectroscopy

Drug discovery

Drug Quality control

Drug incompatibility

On considering the all above aspects of “INFRA RED SPECTROSCOPY”. It is concluded that IR technique is “ an unbound spectroscopic technique for quality optimization from drug discovery to drug quality control parameters”.

41

THANK YOU

42

NOTE:This presentation does not include

plagiarized material.

7 ir interpretatio njntu pharmacy

Education

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