Advanced 2D NMR Techniques Guide

Guided by:
Prof. P.S Pisal Mam
Advance Spectral Analysis
Presented by:
Pratik S. Kapase
M.Pharm 1st year
(Pharmaceutical Chemistry)
2d-nmr;HETCOR,INADEQUATE
AND
DATA INTERPRETATION
PUNE DISTRICT EDUCATION ASSOCIATION’S
SETH GOVIND RAGHUNATH SABLE PHARMACY COLLEGE, SASWAD, PUNE
Subject: Advanced Spectral Analysis

CONTENTS
INTRODUCTION
HETCOR
INADEQUATE
DATA INTERPRETATION
CONCLUSION
REFERENCES
6/16/2023

LEARNING OBJECTIVE
6/16/2023
• To Know About HETCOR.
• To know about INADEQUATE
• To know about Data Interpretation in NMR

INTRODUCTION
2D-NMR
 2D-NMR is a set of nuclear magnetic resonance spectroscopy (NMR) methods which give data plotted in a
space defined by two frequency axes rather than one.
 2D-NMR spectra provide more information about a molecule than one dimensional NMR spectra.
Types of 2D NMR-
• Homonuclear Experiment: In this experiment we provide two frequency to same nuclei in sample. i.e. H-H
Correlation spectroscopy (COSY) Actually in it we basically see homonuclear connectivity between same nuclei.
• Heteronuclear Experiment: In this experiment we provides two frequency to different nuclei in the sample i.e. H-C
Heteronuclear Correlation (HETCOR).

HETCOR
Heteronuclear through-bond correlation methods (HETCOR):
 Heteronuclear correlation spectroscopy gives signal based upon coupling between two different types. Often the two
nuclei are protons and another nucleus (called a "heteronuclear"). For historical reasons, experiments which record
the proton rather than the heteronuclear spectrum during the detection period are called "inverse" experiments.
 This is because the low natural abundance Of most heteronuclear would result in the proton spectrum being
overwhelmed with signals from molecules with no active heteronuclear, making it useless for observing the desired,
coupled signals.
 With the advent of techniques for suppressing these undesired signals, inverse correlation experiments such as
HSQC, HMQC, and HMBC are actually much more common today. 'Normal" heteronuclear correlation
spectroscopy, in which the heteronuclear spectrum is recorded, is known as HETCOR.

 HETCOR Spectrum Of 2-D NMR spectra that show 13C-lH shift correlation are called HETCOR (from
heteronuclear correlation) spectra.
 HETCOR spectra indicate coupling between protons and the carbon to which they are attached.
 Example: 2-methyl-3-pentanone
 The 13C NMR spectrum is shown on the x-axis and the I H NMR spectrum is shown on the y-axis.
 The cross peaks in a HETCOR spectrum identify which hydrogens are attached to which carbons. For example,
cross peak A indicates that the hydrogens that shows a signal at 0.9 ppm in the H-I NMR are bonded to the carbon
that shows a signal at — 6 ppm in the 13CNMR spectrum. Cross peak C shows that the hydrogens that show a
signal at — 2.5 ppm are bonded to the carbon that shows a signal at — 34ppm.

HETCOR of spectrum 2-methyl-3-pentanone

INADEQUATE
 The state for incredible natural abundance double quantum transfer experiment. this experiment is used to
determine of 13C-13C coupling constants in a molecules with natural abundance.
 Magnitude of coupling constant between C-13 nuclei is of great importance to an organic chemist as this is use
for structural elucidation of organic compound 1J(13C13C) is a function of hybridisation of the involved carbon
and the j values are also helpful in establishing connectivity between carbon.
 This experiment does not require 13C,13C double labelling synthetic enrichment becomes possible in a few
exceptional cases. Thus, INADEQUATE is very useful technique and works even in low natural abundance of
C13(1.10%).

Pulse sequence in show in figure
 The basic of the pulse sequence is that by appropriate treatment of spine system that consists of the AX system of
coupled C-13 nuclei and intense signal of parent organic compound with just one C-13,The principal signal can
be supress.
 Obviously ,this requires a 90 phase different between the transverse magnetization of satellites as well as that of
the main signal which allows the selection of AX magnetization for detection.

2-D INADEQUATE
 Thus while the 1-D inadequate experiment lead to the 1D-inadequate experiment lead to the suppression of the
intense 13c-12c main signal with the consequence that both Ax and AB System for all 13c-13c bond can be seen
in a single spectrum, the 2-D version segregates the AB system based upon their individual double quantum
frequencies(DQF) ALONG F2 axis.
 Example: Inadequate spectrum of n-butanol is shown below we can clearly see the segregated AB system for
every C-C bond.
 The arrow enable us to establish the C-C bonds in the molecule from C-1(62.9 ppm)--C-2(36.0 ppm) –C-3
(20.3ppm)—C-4(15.2 ppm).

DATA INTERPRETATION
 Nuclear Magnetic Resonance (NMR) Interpretation Play A Pivotal Role In Molecular Identification as
Interpreting NMR Spectra.
 The Structure Of An Unknown Compound As Well As Known Structure, Can Assigned By several Factor Such
As Chemical Shift, Spin Multiplicity, coupling Constants And Integration.
 Example
1) Methane
2) Benzene
3) Purine
4) Pyrimidine
5) Naphthalene
6) Quinine
7) Ether Derivative

1) Methane
 The NMR Spectrum of Methane CH4 Shows Single Peak.
 The chemical shift of a given Proton is determined primarily by its immediate electronic environment
 Consider the methane (CH4) in which the protons have a chemical shift of 0.23ppm
-3
-2
-1
0
1
2
PPM
Protocol of the C-13 NMR Prediction:
Node Shift Base + Inc. Comment (ppm rel. to TMS)
CH4 -2.3 -2.3 methane
1H-NMR CH4 (-2.3ppm)
0
1
2
PPM
13C NMR CH4 (0.23ppm)
Protocol of the H-1 NMR Prediction:
CH4 0.23 0.23 methane

2) Benzene
7 . 2 6
7 . 2 6
7 . 2 6
7 . 2 6
7 . 2 6
7 . 2 6
CH 7.26 7.26 benzene
0
1
2
3
4
5
6
7
PPM
0
20
40
60
80
100
120
140
PPM
-1.1 general corrections
1 2 7 . 4
1 2 7 . 4
1 2 7 . 4
1 2 7 . 4
1 2 7 . 4
1 2 7 . 4

3) Adenine (Purine)
N
N N
H
N
N H 2
8 .1 2
1 1 .0
8 .6 8
4 .0
0
2
4
6
8
10
PPM
CH 8.12 8.99 purine
-0.87 1 -N from 4-pyrimidine
NH 11.0 11.00 purine
CH 8.68 8.68 purine
NH2 4.0 4.00 aromatic C-NH
N
N N
H
N
NH2
152.4
153.9
119.5
156.1
144.7
0
20
40
60
80
100
120
140
160
PPM
CH 152.4 152.0 purine
0.4 general corrections
C 153.9 154.9 purine
C 119.5 128.4 purine
C 156.1 144.8 purine
CH 144.7 147.9 purine

Cytosine (Pyrimidine ring)
N
H
N
N H 2
O
5 .6 2
7 .3 6
?
?
0
1
2
3
4
5
6
7
PPM
CH 5.62 5.62 cytosine
NH ? n.a. cytosine
NH2 ? n.a. cytosine
0
20
40
60
80
100
120
140
160
180
PPM
N
H
N
N H 2
O
9 3 . 9
1 5 8 . 1
1 6 6 . 9
1 7 1 . 0
C 166.9 166.9 cytosine
C 171.0 171.0 cytosine

1-Naphthylamine(naphthalene)
0
1
2
3
4
5
6
7
PPM
N H 2
7 .3 0
7 .3 1
7 .6 6
7 .6 1
6 .5 5
7 .1 5
7 .1 6
4 .0
CH 7.30 7.32 1-naphthalene
-0.02 1 -N
-0.01 1 -N
-0.01 1 -N
-0.06 1 -N
-0.77 1 -N
-0.17 1 -N
-0.51 1 -N
NH2 4.0 4.00 aromatic C-NH

-0.3 1 -N
-1.3 1 -N
-7.3 1 -N
C 124.7 133.6 1-naphthalene
-10.2 1 -N
0.6 1 -N
0.3 1 -N
14.0 1 -N
-16.5 1 -N
0.3 1 -N
-9.3 1 -N
0
20
40
60
80
100
120
140
PPM
NH2
126.0
125.0
121.0
124.7
134.3
128.6
143.7
109.4
126.6
119.0
1-Naphthylamine (naphthalene)

4,7-DiChloroquine(Quinoline)
0
1
2
3
4
5
6
7
8
PPM
CH 7.43 7.26 quinoline
0.17 1 -Cl from 1-naphthalene
? 1 unknown substituent(s) from 2-naphthalene
-0.04 1 -Cl from 1-naphthalene
0.01 1 -Cl from 1-benzene
0.01 1 -Cl from 1-benzene
-0.06 1 -Cl from 1-benzene
N
C l
C l
7 . 4 3
8 . 7 7
8 . 1 3
7 . 6 0
8 . 1 6

Methoxy Acetic Acid (ether)
0
2
4
6
8
10
PPM
O
O H
O
4 . 3 1
1 1 . 0
3 . 2 4
CH2 4.31 1.37 methylene
2.04 1 alpha -O-C
0.90 1 alpha -C(=O)O
OH 11.0 11.00 carboxylic acid
CH3 3.24 0 .86 methyl
2.38 1 alpha -O-C

O
O H
O
7 2 . 2
1 7 3 . 0
5 8 . 7
0
20
40
60
80
100
120
140
160
180
PPM
CH2 72.2 -2.3 aliphatic
21.8 1 alpha -C(=O)-O
49.0 1 alpha -O
9.4 1 beta -C
C 173.0 166.0 1-carboxyl
10.0 1 -C
CH3 58.7 -2.3 aliphatic
49.0 1 alpha -O
9.4 1 beta -C
-2.8 1 gamma -C(=O)-O
Methoxy Acetic Acid (ether)

REFERENCES:
1.Dr. S.K. Dewan, book of organic spectroscopy, CBS Publication & Distributors PVT.LTD Page No.
335-367.
2. Chemdraw software: for Data interpretation in NMR.

Advanced 2D NMR Techniques Guide

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