Lab Work for This Week •Finish recrystallization of any of the unknowns.

If any of your compounds are not dry, see next page. •Take melting points of the minilab unknown and main lab unknowns •Take IR of main lab unknowns •Take TLC, uses methylene chloride to dissolve your samples and as eluent, of main lab unknowns (one plate for both). Calculate Rf’s of any spots. Turn this in in a baggie (provided) with your lab report)

If any of the melting points, IR’s, or TLC’s are not completed by the time you finish in lab this week, the labs will be open this Saturday and Sunday, both from 1-4pm. You may not do any wet chemistry (separations, recrystallizations, filtrations). Dress as you would normally come to lab. Enter Hutchison Hall on the Plaza level (second floor).

Lab reports due next week •Discuss the solubility data you collected the first week of the experiment •Discuss what techniques were employed to decide which unknowns you have. You do not (cannot) decide the structure of the minilab compound. Just report it’s slow melting point range. •Calculate the recrystallized yield of the minilab unknown and the main two main lab unknowns •Discuss the IR’s taken •Discuss the TLC taken •Answer questions from website posted last week.

Nuclear Magnetic Resonance Introduction

This introduction is designed to explain Nuclear Magnetic Resonance Spectroscopy (NMR), which is now the main structure determination tool used by organic chemists. This technique can be used to determine the structures of virtually all organic compounds, no matter how complex. It is even being used to determine very complex structures such as enzymes and proteins. NMR produces a spectrum containing a number of peaks. The heights and positions of these peaks enable a chemist to very accurately determine what the carbonhydrogen framework of an organic molecule is.

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NMR Introducti on

What is Nuclear Magnetic Resonance Spectroscopy?
NMR is a spectroscopic technique which uses electromagnetic radiation and magnetic fields to determine the structure of organic compounds. Radio-frequency radiation is used to stimulate nuclei present within the molecule and from the information we obtain from doing this we can very accurately determine where the carbon atoms are located and where hydrogen atoms are located.
Basics: Nuclei with an odd mass or odd atomic number have "nuclear spin" (in a similar fashion to the spin of electrons). This includes 1H and 13C (but no t 12C). The spins of nuclei are sufficiently different that NMR experiments can be sensitive for only one particular isotope of one particular element. The NMR behavior of 1 H and 13C nuclei has been exploited by organic chemist since they provide valuable information that can be used to deduce the structure of organic compounds. These will be the focus of our attention.
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Since a nucleus is a charged particle in motion, it will develop a magnetic field. 1H and 13C have nuclear spins of 1/2 and so they behave in a similar fashion to a simple, tiny bar magnet. In the absence of a magnetic field, these are randomly oriented but when a field is applied they line up parallel to the applied field, either spin aligned or spin opposed. The more highly populated state is the lower energy spin state spin aligned situation. Two schematic representations of these arrangements are shown below:

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In NMR, EM radiation is used to "flip" the alignment of nuclear spins from the low energy spin aligned state to the higher energy spin opposed state. The energy required for this transition depends on the strength of the applied magnetic field (see below) but in is small and corresponds to the radio frequency range of the EM spectrum. As this diagram shows, the energy required for the spin-flip depends on the magnetic field strength at the nucleus. With no applied field, there is no energy difference between the spin states, but as the field increases so does the separation of energies of the spin states and therefore so does the frequency required to cause the spin-flip, referred to as resonance.

The basic arrangement of an NMR spectrometer is shown to the left. The sample is positioned in the magnetic field and excited via pulsations in the radio frequency input circuit. The realigned magnetic fields induce a radio signal in the output circuit which is used to generate the output signal. Fourier analysis of the complex output produces the actual spectrum. The pulse is repeated as many times as necessary to allow the signals to be identified

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from the background noise.

Types of Nuclei

There are many nuclei which are NMR active. The table below shows some of the more common ones. Despite this, most NMR data are collected for 1H and 13C since they are so important in organic chemistry.
Isotope % abund Nuclear spin 1 H 99.985 1/2
13 2

C B N F P

1.108 0.015 80.42 99.63 100 100

1/2 1 3/2 1 1/2 1/2

H

11 14 19 31

NMR Active Isotopes

NMR sample preparation: NMR tube: usually 5mm across and 5 or 7 inches in length. In the NMR tube goes an approximate 1% solution of the compound under investigation and a solvent. But not any solvent!
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If one had a 1% solution of cyclohexane in chloroform, the proton in chloroform would overwhelm the signal for cyclohexane. Thus, one uses a deutersolvent, like CDCl3, aka deuterochloroform or chloroform-d.

In the complete interpretation of an NMR, there are four questions to answer: 1) How many unique observations are there? 2) Where are these unique observations located? 3) What are the nearby neighbors of the observations in question? 4) How many H’s of each unique observation are there?

We will answer the first two questions this week, and the last two questions we’ll answer in the next two weeks.

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1) How many unique observations are there?

Let’s look at a few examples:

CH3CH3

H H

H H

H H

CH3CH2CH3

CH3CH2CH2CH3

CH 3 CH3 C CH2CH 3 H

CH 3 CH3 C CH2CH 3 CH 3

H H

C C

H H

H H

C C

CH 3 H

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How many unique observations are there?

Let’s look at a few examples:

one

CH3CH3

H H

H H

H H

two

CH3CH2CH3

CH3CH2CH2CH3

two

four

CH 3 CH3 C CH2CH 3 H

CH 3 CH3 C CH2CH 3 CH 3

three

H H

C C
One

H H

H H

C C

CH 3 H

four

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2) Where are these unique observations located? Chemical Shift

• •

An NMR spectrum is a plot of the radio frequency applied against absorption . A signal in the spectrum is referred to as a resonance . The frequency of a signal is known as its chemical shift .

The chemical shift in absolute terms is defined by the frequency of the resonance expressed with reference to a standard compound which is defined to be at 0 ppm. The scale is made more manageable by expressing it in parts per million (ppm) and is indepedent of the spectrometer frequency.

It is often convienient to describe the relative positions of the resonances in an NMR spectrum. For example, a peak at a chemical shift, δ, of 10 ppm is said to be downfield or deshielded with respect to a peak at 5 ppm, or if you prefer, the peak at 5 ppm is upfield or shielded with respect to the peak at 10 ppm.

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NMR spectra usually are displayed like the one below with the applied field strength increasing from left to right and the intensity of absorption plotted on the vertical axis.

O Cl CH2 C CH3

Chloropropanone In order that we get consistent positions for absorptions we add an internal standard, usually TMS (tetramethylsilane, (CH3)4Si). The protons in this compound are all identical and are assigned a chemical shift of zero. It is selected for both 1H and 13C spectra because its single peak occurs upfield of almost all other absorptions. The chemical shift is the name given to the position in the spectrum at which an absorption occurs. The horizontal scale is measured in delta or parts per
10

million (ppm), 1 ppm is 1 part per million of the spectrometer frequency. For example, if we used a 200 MHz spectrometer, we would have each ppm would be equal to a separation of 200 Hz. The reason for this is that there are many different spectrometers available, operating at many different frequencies, and so to eliminate any variability from one instrument to another this system is used.

So what causes chemical shift?
Shielding in H-NMR
The magnetic field experienced by a proton is influenced by various structural factors. Since the magnetic field strength dictates the energy separation of the spin states and hence the radio frequency of the resonance, the structural factors mean that different types of proton will occur at different chemical shifts. This is what makes NMR so useful for structure determination, otherwise all protons would have the same chemical shift. The various factors include:
• • •

inductive effects by electronegative groups magnetic anisotropy hydrogen bonding

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Electronegativity
The electrons around the proton create a magnetic field that opposes the applied field. Since this reduces the field experienced at the nucleus, the electrons are said to shie ld the proton. It can be useful to think of this in terms of vectors....

Since the field experienced by the proton defines the energy difference between the two spin states, the frequency and hence the chemical shift, δ /ppm, will change depending on the electron density around the proton. Electronegative groups attached to the C-H system decrease the electron density around the protons, and there is less shielding (i.e. deshielding) so the chemical shift increases. This is reflected by the plot shown in the graph to the left which is based on the data shown below.
Compound, CH3X X Electronegativity of X Chemical shift, δ / ppm 12 CH3F F 4.0 4.26 CH3OH O 3.5 3.4 CH3Cl Cl 3.1 3.05 CH3Br Br 2.8 2.68 CH3I I 2.5 2.16 CH4 H 2.1 0.23 (CH3)4Si Si 1.8 0

These effects are cumulative, so the presence of more electronegative groups produce more deshielding and therefore, larger chemical shifts.

Compound δ / ppm

CH4 0.23

CH3Cl 3.05

CH2Cl2 5.30

CHCl3 7.27

These inductive effects are not just felt by the immediately adjacent protons as the disruption of electron density has an influence H signal -CH2-CH2-CH2Br further down the chain. However, δ / ppm 1.25 1.69 3.30 the effect does fade rapidly as you This is known as the β effect move away from the electronegative group. As an example, look at the chemical shifts for part of a primary bromide

Magnetic Anisotropy
The word "anisotropic" means "non-uniform". Magnetic anisotropy means that there is a "non-uniform magnetic field". Electrons in p systems (e.g. aromatics, alkenes, alkynes, carbonyls etc.) interact with the applied field which induces a magnetic field that causes the anisotropy. As a result, the nearby protons will experience 3 fields: the applied field, the shielding field of the valence electrons and the field due to the p system. Depending on the position of the proton in this third field, it can be either shielded (smaller δ) or deshielded (larger δ), which implies that the energy required for, and the frequency of the absorption will change.

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Hydrogen Bonding
Protons that are involved in hydrogen bonding (this usually means -OH or -NH) are typically observed over a large range of chemical shift values. The more hydrogen bonding there is, the more the proton is deshielded and the higher its chemical shift will be. However, since the amount of hydrogen bonding is susceptible to factors such as solvation, acidity, concentration and temperature, it can often be difficult to predict. HINT : It is often a good idea to leave assigning -OH or -NH resonances until other assignments have been made. Experimentally, -OH and -NH protons can be identified by carrying out a simple D 2 O (deuterium oxide, also known as heavy water) exchange experiment.

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• • • •

Run the regular H-NMR experiment Add a few drops of D2O Re-run H-NMR experiment Compare the two spectra a look for peaks that have "disappeared"

Why would a peak disappear? Consider the alcohol case for example: R-OH + D 2 O <=> R -OD + HOD During the hydrogen bonding, the alcohol and heavy water can "exchange" -H and -D each other, so the alcohol becomes R-OD. Although D is NMR active, its’ signals are of different energy and are not seen in the H-NMR, hence the peak due to the -OH disappears. (Note that the HOD will appear...)

The range in which NMR absorptions occurs is quite narrow. 1H absorptions occur normally in the range 0 - 12 ppm downfield from TMS.

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Aromatic Vinylic Protons

Protons on C

Protons Attached to Electronegative atoms

Allylic Alkanes

Saturated Alkanes

8.0

6.5

4.5

2.5

1.5

0

0-1.5 H on a sp3 C next to a sp3 C. 1.5-2.5 H on a sp3 C next to a sp2 C. 2.5-4.5 H on a sp3 C next to a heteroatom (w/ lone pair of electrons) 4.5-6.5 H on a sp2 C 6.5-8.0 H on an aromatic (benzene) ring
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CH3CH2CH3

CH3CH2CH2CH3

H H

C C

H H
H

H H

C C

CH 3 H

H

β-effect – Add 0.5 ppm to the expected range (01.5); now 0.5-2.0.

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