INTRDUCTION

In 1946, NMR was co-discovered by Purcell, Pound and Torrey of Harvard University and Bloch,
Hansen and Packard of Stanford University. The discovery first came about when it was noticed
that magnetic nuclei, such as 1H and 31P (read: proton and Phosphorus 31) were able to absorb
radio frequency energy when placed in a magnetic field of a strength that was specific to the
nucleus. Upon absorption, the nuclei begin to resonate and different atoms within a molecule
resonated at different frequencies. This observation allowed a detailed analysis of the structure of a
molecule. Since then, NMR has been applied to solids, liquids and gasses, kinetic and structural
studies, resulting in 6 Nobel prizes being awarded in the field of NMR.

Nuclear magnetic resonance (NMR) spectroscopy is an analytical technique used in quality control
and research for determining the content and purity of a sample as well as its molecular structure. It
is a technique that exploits the magnetic properties of nuclei. It determines the physical and
chemical properties of atoms or the molecules in which they are contained.

BODY

Nuclear magnetic resonance spectroscopy, most commonly known as NMR spectroscopy or

magnetic resonance spectroscopy (MRS), is a spectroscopic technique to observe local magnetic
fields around atomic nuclei. It is a spectroscopy technique which is based on the absorption of
electromagnetic radiation in the radio frequency region 4 to 900 MHz by nuclei of the atoms. Over
the past fifty years, NMR has become the preeminent technique for determining the structure of
organic compounds. Of all the spectroscopic methods, it is the only one for which a complete
analysis and interpretation of the entire spectrum is normally expected.

Figure 1: Nuclear Magnetic Resonance (NMR)Spectroscopy

PRINCIPLE
The principle behind NMR is that many nuclei have spin and all nuclei are electrical charged.

If a n eternal magnetic field d is applied, an energy transfer is possible between the base energy to
a higher energy level (generally a single energy gap).
The energy transfer takes place at a wavelength that corresponds to radio frequencies and when
the spin returns to its base level energy is emitted at the same frequency.

THEORY
When a charged particle such as a proton spins on its axis, it creates a magnetic field. Thus, the
nucleus can be considered to be a tiny bar magnet.

Normally, these tiny bar magnets are randomly oriented in space. However, in the presence of
magnetic field Bo, they are oriented with or against this applied field.

In a magnetic field (Bo), there are now two energy states for a proton: a lower energy state with the
nucleus aligned in the same direction as Bo, and a higher energy state in which the nucleus aligned
against B0.

Thus, two variables characterize NMR: an applied magnetic field Bo, the strength of which is
measured in tesla (T), and the frequency of radiation used for resonance, measured in hertz

Figure 2: Effect of magnetic field

The frequency needed for resonance and the applied magnetic field strength are proportionally

related:

Figure 3: Resonance Frequency

The stronger the magnetic field, the larger the energy difference between

The two nuclear spin states, and the higher the  needed for resonance.

Nuclear Resonance
A proton in a static filed may assume only two orientations corresponding to energies +/-  μH. The
low energy orientation and high energy orientation.
The precessional frequency of the spinning nucleus is eactly equal to the frequency of
electromagnetic radiation necessary to induce a transition from one nuclear spin state to another.
When the frequency of rotating magnetic field and the frequency of precessing nucleus becomes
equal they are said to be in resonance. Spontaneous transition from higher energy state to lower
energy state is negligible in radio frequency region.

Chemical shift
A chemical shift is defined as the difference in parts per million (ppm) between resonance frequency
of observed proton to tetraethylsilane (TMS) hydrogen. TMS is common reference standard used in
NMR, it is set a d= 0 ppm.

Shielding
High electron density around the nucleus shields the nucleus from eternal magnetic field and the
signals are up field in the NMR spectrum.

Factors affecting chemical shift

-electronegative group
-electronegative group attached to C-H system decreases the electron density around the proton
and there is less shielding this chemical shift increases,
-magnetic anisotrophy
-hydrogenbonding

INTRUMENTATION

There are two types of NMR spectrometers, continuous-wave (cw) and pulsed or Fourier-Transform
(FT-NMR)

Fourier-Transform NMR spectrometers use a pulse of radiofrequency radiation to cause nuclei in a

magnetic field to flip into the higher-energy alignment. The length of the RF pulse is 1-10 µs and is
wide enough to simultaneously excite nuclei in all local environments. The interval between pulses T
is typically one to several seconds. During T, a time-domain RF signal called the free induction
decay (FID) signal is emitted as nuclei return to their original state.

A continuous-wave NMR instrument consists of the following units: a magnet to separate the
nuclear spin energy states; at least two radiofrequency channels, one for field/frequency
stabilization and one to furnish RF irradiation energy; a sample probe containing coils for coupling
the sample with the RF field; a detector to process the NMR signals; a sweep generator for
sweeping either the magnetic or RF field through the resonance frequencies of the sample; and a
recorder to display the spectrum.

This instrument consists of nine major parts. They are discussed below:

Sample holder- Glass tube with 8.5 cm long, 0.3 cm in diameter.

Permanent magnet- It provides homogeneous magnetic field at 60-100 MHZ

Magnetic coils-These coils induce magnetic field when current flows through them

Sweep generator-To produce the equal amount of magnetic field pass through the sample

Radio frequency transmitter-A radio transmitter coil transmitter that produces a short powerful pulse
of radio waves

Radio frequency receiver-A radio receiver coil that detects radio frequencies emitted as nuclei relax
to a lower energy level

RF detector – It helps in determining unabsorbed radio frequencies.

Recorder – It records the NMR signals which are received by the RF detector.

Read out systems-A computer that analyses and record the data.

Figure 4: Instrumentation of NMR Spectroscopy

HOW DOES NMR SPECTROSCOPY WORK?

The sample is placed in a magnetic field and the NMR signal is produced by excitation of the nuclei
sample with radio waves into nuclear magnetic resonance, which is detected with sensitive radio
receivers.

The intramolecular magnetic field around an atom in a molecule changes the resonance frequency,
thus giving access to details of the electronic structure of a molecule and its individual functional
groups.

As the fields are unique or highly characteristic to individual compounds, NMR spectroscopy is the
definitive method to identify monomolecular organic compounds.

Besides identification, NMR spectroscopy provides detailed information about the structure,
dynamics, reaction state, and chemical environment of molecules.

The most common types of NMR are proton and carbon-13 NMR spectroscopy, but it is applicable
to any kind of sample that contains nuclei possessing spin.
APPLICATION OF NMR SPECTROSCOPY IN PHARMACEUTICAL ANALYSIS

NMR SPECTROSCOPY is a primary method of measurement and it can be also used to evaluate
the quality of drugs and excipients besides the possibility to identify a drug by the comparison of the
H or C NMR spectra of the substance to be examined and a reference substance. Nuclear magnetic

Resonance (NMR) spectroscopy is an extremely powerful tool for the detection, identification, and
quantification of drugs and related substances.

Although, NMR has been used for many years to analyze drugs, even the most modern
spectrometers lack the sensitivity obtainable by other techniques such as mass spectrometry or
high performance liquid chromatography.

In pharmaceutical industry, the LC-NMR is being routinely used for the identification of impurities,
drug intermediates, combinatorial chemistry, separation of pharmaceutical mixtures etc. NMR
spectroscopy is considered as a primary method for the measurement of ratios.

DISCUSSION

As we go on Nuclear magnetic resonance spectroscopy also known as NMR stectroscopy we can

discuss about it further more. Nuclear magnetic resonance spectroscopy or NMR is used quality
control and research for determining the content and purity of a sample as well as its molecular
structure. We can also discuss that NMR spectroscopy can also be used the evaluate the quality of
drugs and its excipients. NMR is a very powerful tool detention, identification and most specially for
quantification of drugs and related substances. Therefore, NMR can be a useful tool not only today's
generation but as generation pass by and innovation is still on its peak NMR can be more
developed and can be more helpful and useful in the future for pharmaceutical analysis.

Summary

Nuclear Magnetic Resonance (NMR) spectroscopy is an analytical chemistry technique used in

quality control and research for determining the content and purity of a sample as well as its
molecular structure. For example, NMR can quantitatively analyze mixtures containing known
compounds. For unknown compounds, NMR can either be used to match against spectral libraries
or to infer the basic structure directly. Once the basic structure is known, NMR can be used to
determine molecular conformation in solution as well as studying physical properties at the
molecular level such as conformational exchange, phase changes, solubility, and diffusion. In order
to achieve the desired results, a variety of NMR techniques are available.

REFERENCES
John r. Dyer, application of absorption spectroscopy of organic compounds, 1965, PHI learning
Pvt.Ltd., Page no58-132

Chapter 13. Nuclear Magnetic Resonance Spectroscopy. Jo Blackbrun. Richand College, Dallas.
TX. Dallas country Community College District.

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