Organic Structure Determination 1

Analytical Chemistry

Instrument-based methods for determination of structure of organic molecules

1) Mass Spectrometry - yields molecular weight/elements/possible molecular formulas

2) Infrared Spectroscopy - yields functional groups

3) NMR Spectroscopy - very important, yields structure - described in the NEXT SECTION OF THE NOTES

1  Mass Spectrometry

• Gives molecular weight, some elemental information, possible molecular formulas (and degrees of unsaturation)

• The sample is vaporized by heating under vacuum, then ionized by removal of an electron in an electron beam, high energy electrons impacting an organic molecule in vacuum can actually REMOVE an electron (there are other ionization techniques but this is the historically important method)

• After ionization the species is a radical AND a cation, a radical cation, that has had an electron removed, usually, from a bonding MO, which weakens the bonds and results in fragmentation of several bonds to form radicals and cations

• Usually not all of the original radical cations fragment, some remain intact, and a mixture of the radical cation and cation fragments results

For Example: Butane

• The various cations are positively charged and are accelerated towards a negatively charged electrode, the electrode has a small hole in it and some ions pass through into a tube with a variable magnet

• Moving charged particles such as cations generate a magnetic field, which interacts with the field of the variable magnet to deflect the path of the cation

• Different cations have different masses and therefore different momenta, and are deflected to different extents

• Depending upon the mass (momentum) of the cation, it can be deflected exactly enough to pass through a slit at the end of the tube and be detected electronically

• Varying the external magnetic field selects cations with different masses to be detected, and so scanning the external field generates a scan over the masses of the various cations and generates a MASS SPECTRUM

An Idealized mass spectrum of butane...

• mass spectrum is plot of ion current (i.e. # of ions) versus mass/charge ratio (m/z), where z is charge

 • because the charge is almost always positive one (multi-charged species are rarely encountered in mass spectra), m/z is essentially the same as mass

• the largest m/z value corresponds to "molecular ion", i.e. the unfragmented radical cation and this gives the molecular weight of the molecule being analyzed

• the molecular ion peak not necessarily the most "abundant", i.e. it is often not the "tallest" peak (called the base peak), but it has the largest m/z

• It is IMPORTANT TO REMEMBER that the sample being analyzed contains millions and millions of molecules, the peaks that are observed in the mass spectrum can NOT come from a single molecule, many of the molecules fragment in the spectrometer to generate the ion peaks with lower mass, some of them do not fragment and generate the molecular ion peak, the different fragment differently (or not at all) because they have a distribution of energies as a result of the ionization process.

• there is a lot of structural information in a mass spectrum but we will IGNORE MOST OF IT and focus only on the molecular ion peak

1.1  Important Information from Molecular Ion Peaks

A compound that contains the elements C, H and O only : The molecular ion mass is an even number

• the most abundant (largest) peak is not that of the molecular ion, it is of a fragment, the molecular ions will have the LARGEST mass, since it has not fragmented

• the M+1 peak is due to molecules that contain the isotopes D, ¹³C, etc., we should expect to see an M+1 peak at ca. 10% of the intensity of the molecular ion peak

• an even numbered molecular weight means that the molecular contains carbon and hydrogen, and possibly (but not necessarily) oxygen.  There is no specific "signature" for oxygen in mass spectrometry.

A compound that contains the element Br: The mass spectrum has TWO molecular Ion Peaks

• the mass spectrum has TWO molecular ions, one for the molecules that contain 79Br, and one for the molecules that contain 81Br

• these two molecular ion peaks are separated by 2 mass units and have ca. 1:1 size ratio

A compound that contains the element Cl: The mass spectrum has TWO molecular Ion Peaks

• the mass spectrum has TWO molecular ions, one for the molecules that contain 35Cl, and one for the molecules that contain 37Cl

• these two molecular ion peaks are separated by 2 mass units and have ca. 3:1 size ratio

A compound that contains the element N : The molecular ion mass is an ODD number for 1 or 3 N atoms

• odd molecular weight means a single nitrogen (the M.W. for 2, 4, 6 etc. nitrogens would be even)

• strictly speaking, any odd number of N atoms, but usually one in this class

1.2  Important Information From Molecular Weight

• Determine Possible Molecular Formula from Mass Spectrum

• What are POSSIBLE and also REASONABLE molecular formulae for this mass spectrum?

• Possible molecular formula will not have more than the maximum number of hydrogen atoms calculated the usual way for degrees of unsaturation

• Unreasonable molecular formulae are harder to define, they will generally have at least as many carbon atoms as hydrogen atoms and more hydrogen atoms than oxygen atoms, but there are some exceptions to these "rules"

• Divide MW by 12 to determine maximum possible number of H atoms, the remainder (R) is equal to the mass of the H atoms, the arithmetic process used to determine possible molecular formulae is…..

divide M.W. by 12 = 100/12 = 8 (R4) : the maximum number of carbons = 8

C₈H₄ is possible (7 degrees of unsaturation, BUT not reasonable (too few H atoms))

• replace 1 C atom by 12 H atoms, maintains the correct MW

C₇H₁₆ is possible AND reasonable   (0 degrees of unsaturation)

• replace 1 C atom and 4 H atoms by 1 O atom, maintains correct MW

C₆H₁₂O (1 degree)

and     C₅H₈O₂ (2 degrees)

and     C₄H₄O₃ (3 degrees)

these 3 are both possible AND reasonable

Thus, there are FOUR possible AND reasonable molecular formulae for M.W. = 100

2  Infrared Spectroscopy

• molecules at room temperature are very hot, they don't SEEM to be very hot, but RELATIVE TO ABSOLUTE ZERO (where molecules have essentially no energy), molecules at room temperature have a lot of energy (they are hotter by 273 degrees C), and this energy has to "go" somewhere.

• In molecules this energy goes into kinetic energy if they are in the gas or liquid phase, but importantly also into BOND VIBRATIONS

Electromagnetic Radiation  (light!)

• Electromagnetic radiation consists of an oscillating orthogonal (right angles) electric and magnetic fields

• the energy in electromagnetic radiation is determined by the oscillation frequency of the electric (and magnetic) field vectors, and is given the symbol Greek n (pronounced "nu" and which looks sort of like a v)

• the energy in electromagnetic radiation is ALSO determined by the wavelength of the electric (and magnetic) field vectors, and is given the symbol Greek l (pronounced "lambda" and which looks sort of like a v)

• the wavelength and frequency of electromagnetic radiation are related via the speed of light

• we do not need to get into these equations in detail (although they are quite simple), what we need to know is that energy in electromagnetic radiation is DIRECTLY proportional to frequency, and INVERSELY proportional to wavelength, i.e, ENERGY INCREASES with INCREASING FREQUENCY

The Electromagnetic Spectrum

• the range of frequencies of the electromagnetic radiation in the infrared region matches the range of frequencies of vibrations of bonds in molecules

• if the frequency of the infrared radiation exactly matches that of a particular bond vibration in a molecule, then the electric field vector of the radiation can interact with the dipole moment of the vibrating bond, the radiation can be absorbed by the molecule and used to increase the bond vibration amplitude

• the electromagnetic frequency must EXACTLY match the frequency of VIBRATION of the bond (IR absorption is quantized), if the frequency is higher or lower than the bond vibration frequency it will not be absorbed

• for IR radiation to interact with a vibrating bond, the bond MUST HAVE A DIPOLE MOMENT

2.1  A Real Infrared Spectrum

• Infrared Vibrations are often localized on bonds or groups of atoms (the more useful vibrations are localized on specific bonds)

• Different bonds vibrate with different frequencies, this is important as this is the basis for identifying different bonds/functional groups in a spectrum, and hence in a structure

• We need to know about how many bond vibrations are possible, what their frequencies are also how STRONG or WEAK the absorptions are, i.e. how "big" they appear in actual spectra

1) How Many Bond Vibrations Are Possible in a Molecule?

•  for n atoms there are MANY POSSIBLE vibrations, in fact (3n + 6)!

• however, many of these are complex, i.e. are not localized on individual bonds, and occur with lower frequencies (less than 1500 cm-1) in the "fingerprint region", which is the area that has signals that are specific to a particular molecule, not to a specific functional group, in this class we ignore the fingerprint region

2) What are the BOND Vibrational Frequencies?

• vibrational frequencies are determined by bond strength and atomic mass

• A bond as "spring" analogy is useful

• bonds have HIGH VIBRATION FREQUENCIES if they are STRONG, and have consist of LIGHT ATOMS

• bonds have LOW VIBRATION FREQUENCIES if they are WEAK, and have consist of HEAVY ATOMS

• a strong bond (spring) vibrates with a higher frequency

• a bond (spring) with small/light atoms attached will vibrate with a higher frequency

Visualize the how stronger bonds and lighter atoms result in higher vibrational frequencies

Approximate Regions in the Infrared Spectrum

• bonds to the very light atom H have the highest vibrational frequencies, stronger bonds to H having the highest frequencies

• triple bonds to heavier atoms come next

• double bonds to heavier elements come next, with higher frequencies for stronger bonds

• single bonds to heavier elements have the lowest frequencies, usually in the fingerprint region where identifying functional groups is difficult, and is not included in this course

3) How strong are the Absorption Peaks (how big are the peaks in the spectra)?

• the electric field vector of the electromagnetic radiation interacts with dipole moment of the vibrating bond

• when the DIRECTION OF THE electric field (vector) of the IR electromagnetic radiation is ALIGNED with the DIRECTION OF THE BOND DIPOLE MOMENT the field can "pull" the atoms apart (if the frequency is matched) and thus increase the amplitude of the vibration (the atoms separate more), in this way the IR energy is absorbed into the molecule, the energy is "used" to make the bind vibrate with a larger amplitude

• it may seem unlikely that the electric field and the bond dipole line up exactly, but in fact there are billions of molecules that are constantly tumbling in space which means that there will be plenty of bonds in the correct alignment, especially because the alignment doesn’t have to be perfect

• large (change in) dipole moment results in stronger interactions with the electric field vector, which result sin absorption of a lot of IR radiation which in turn results strong IR absorptions

• to be observed in an IR spectrum a bond has to have a dipole moment

• bonds with LARGER DIPOLE moments interact more strongly with the electric field vector of the electromagnetic radiation and have STRONGER (LARGER) absorption signals in an IR spectrum

EXAMPLES:

2.2  Real Absorption Bands

Vibrations of C-H bonds around 3000 cm^-1 (2700 - 3500 cm^-1 = bonds to H atoms)

• H atoms are LIGHT, bonds to H atoms tend to be high frequency (large nu), ca. 2700 - 3500 cm-1

• stronger C-H bonds will vibrate with higher frequencies, weaker C-H bonds will vibrate with lower frequencies

• We KNOW SOMETHING about C-H bond strengths……

•  We EXPECT that stronger C-H bonds will have higher frequency absorption in IR spectroscopy, and they do!

• peaks due to C-H vibrations that are found at frequencies less than 3000 cm-1 are due to H atoms that are attached to sp3 hybridized carbons. Bonds from hydrogen to sp3 carbons are somewhat weaker than bonds to, e.g. sp2 hybridized carbons, and thus are found at somewhat lower frequencies

• the dipole moments for C-H bonds are very small, HOWEVER, there are usually LOTS of C-H bond vibrations, and so they "add up" so that the peaks can still be observed in the spectrum

• peaks due to C-H vibrations that are found at frequencies just above 3000 cm-1 are due to H atoms that are attached to sp2 hybridized carbons. Bonds from hydrogen to sp2 carbons are somewhat stronger than bonds to sp3 hybridized carbons, and thus are found at somewhat higher frequencies

• C-H vibrations around 3300 cm-1 are due to H atoms that are attached to sp hybridized carbons. These are stronger bonds with higher vibrational frequencies. They are distinguished from O-H and N-H bonds by the fact that they are not broad

Vibrations greater than 3000 cm^-1 (2700 - 3500 cm^-1 = bonds to H atoms)

• Bonds between hydrogen and other elements are also expected to have high frequency vibrations

• AND, bonds to more electronegative elements than carbon are stronger and are thus expected to vibrate with higher frequencies

• We therefore EXPECT that bonds to more electronegative elements should have higher vibration frequencies because they are stronger

•  N-H and O-H bonds ALSO HAVE larger dipole moments, their IR absorption peaks should be STRONGER

• The O-H bond vibration IS at higher frequencies than C-H bond vibrations, ca. 3300 cm-1, AND it is strong due to the large bond dipole moment, ONE O-H bond is equivalent to many C-H bonds in absorption strength

• The alcohol O-H stretching vibration is BROAD due to HYDROGEN-BONDING, Hydrogen-bonding "pulls" the H "away" from the O, resulting in a lower frequency vibration, a distribution in Hydrogen-bonding results in a distribution in frequencies which results in a BROAD absorption band

• The absorption is centered at ca. 3300 cm-1, which distinguished alcohols from carboxylic acids (see later)

• The amine N-H stretching vibration is also broad due to hydrogen-bonding, but N-H hydrogen bonding is WEAKER than O-H Hydrogen bonding (nitrogen is less electronegative than oxygen), and some non-hydrogen bonded N-H vibrations can be observed as small sharp peaks on top of the broad absorption

• The N-H bond dipole is also smaller than the O-H bond dipole (N less electronegative than O) and so N-H absorptions tend to be somewhat weaker than O-H absorptions

• There are usually 2 small (non hydrogen-bonding) peaks for a primary amine that has two N-H bonds

• There is usually 1 small (non hydrogen-bonding) peak for a secondary amine that has one N-H bond

 • Of course, a tertiary amine has no N-H bonds and no signals at all are observed in this region in this case.

Vibrations of other bonds to Hydrogen around 3000 cm-1 (2700 - 3500 cm^-1 = bonds to H region)

• Aldehydes have 2 small peaks around 2730 and 2820 for the single C-H bond that is attached to the C=O

• These are sometimes difficult to distinguish, and can range between ca. 2720 - 2740 and ca. 2810 - 2830, but the aldehyde also has the strong C=O stretching vibration at ca. 1700 cm-1 (see further below).  Observations of BOTH vibrational features helps to identify an aldehyde

• The aldehyde C-H stretching vibration has a lower frequency than other C-H bonds due to electron withdrawal from the C-H bond by the electronegative oxygen

• NOTE: TWO ABSORPTION SIGNALS OBSERVED FOR CARBOXYLIC ACIDS (O-H and C=O)

• Carboxylic acids have a broad O-H peak for the same reason that alcohols do, hydrogen bonding, however, the hydrogen bonding is STRONGER in carboxylic acids, which results in a lower frequency O-H stretching vibration compared to an alcohol due to a larger "pull" on the H atom away from the oxygen

• The stronger hydrogen bonding also results in a very broad absorption band broad absorption band that is distinguished from the alcohol O-H in that it is centered around 3000 cm-1, basically right in top of the usual C-H region

• Carboxylic acids are also distinguished from alcohols by having the C=O stretching vibration at ca. 1700 cm-1 that is very strong (see later).

Vibrations around 2500 - 1700 cm^-1 (2000 - 2500 cm^-1 = triple bond region)

•  Bonds to atoms heavier than hydrogen vibrate with lower frequencies, the strongest of these are triple bonds

• There are only two kinds of vibrations observed in this region, the C-N triple bond of the nitrile functional group and the C-C triple bond of the alkyne functional group

• The C-N triple bond absorptions due to nitrile tend to be strong because the dipole moment associated with this bond is VERY large!

• Carbon-carbon triple bond absorptions tend to be somewhat weak (the bonds have very small dipole moments) and are only usually observed for the asymmetrical terminal alkynes (alkynes in which one carbon is attached to hydrogen, the other to an alkyl or aryl group). Internal alkynes that have alkyl groups attached to both ends of the triple bond are too symmetrical, too small dipole moments and are usually not observed

• For terminal alkynes of course, the H-C(sp) vibration is also observed at ca. 3300 cm-1.

Vibrations Around 1850 – 1600 cm^-1 (1600 - 1850 cm^-1 = double bond region)

• This is an important region of the IR spectrum, as usual, stronger bonds vibrate at higher frequencies, which means that C=O double bonds are expected higher vibrational frequencies than C=C double bonds, and they do

• C=O bonds also have larger bond dipole moments than C=C bonds, and should have stronger absorptions than C=C bonds, and they do

• Vibrations of the C=O bond in aldehydes and ketone are VERY strong and occur close to 1700 cm-1, often ca. 1710-1715 cm-1.

• Aldehdyes can be distinguished from ketones because they also have the 2 peaks due to C-H vibration at ca. 2730 and 2820 cm-1 (which means the spectrum above must be of a ketone because these peaks are absent)

• C=C double bonds tend to have small dipole moments and are usually have weak (small) absorptions, the bonds are also weaker than C=O bonds and vibrate with lower frequencies, ca. 1620 cm-1

Different C=O Vibrations Around 1730 – 1680 cm^-1 (1600 - 1850 cm^-1 = double bond region)

• Small changes in the C=O bond strength can be detected in small changes in the C=O vibration frequency

• These small changes can be quite reliable and can be used to distinguish various kinds of C=O bonds

• The electronegative oxygen that is connected to the C=O bond in the ester makes all of the bonds stronger, including the C=O bond, thus, ester C=O vibrations occur at relatively high frequencies, around 1720 - 1730 cm-1

• Even though this is only slightly higher than the normal frequencies for C=O bond vibrations in aldehydes and ketones it is diagnostic enough to distinguish most esters from ketones

• "Conjugated" ketones have a C=C bond adjacent to the C=O bond, the minor resonance contributor illustrates that the C=O bond has some single bond character in these cases. The more important the minor resonance contributor, the more single bond character (the C=O is less of a pure double bond), the weaker the bond, the lower the vibrational frequency

•  conjugated aldehydes and ketones have vibration frequencies around 1680 cm-1, the difference compared to non-conjugated aldehydes and ketones (ca. 1710 cm-1) is reliable enough to distinguish these cases

• The minor resonance contributor for the amide also shows that the C=O bond has some single bond character

• In the case of an amide the minor resonance contributor is even more important than the minor contributor in the conjugated system above, because the electrons that are involved in resonance "start" as non-bonding on the nitrogen and are thus higher energy than those in the double bond above, and are thus more "available" for resonance, the minor contributor here is "less minor"

•  the vibration frequency is thus further decreased to ca. 1640 cm-1.  Just like amines, the amide will have N-H vibrations (with peaks) in the 3300 cm-1 region

MOLECULAR vibration at 1600 cm^-1 (1600 - 1850 cm^-1 = double bond region)

• There is one final vibration that is UNUSUAL in that it is not of a single bond, but is associated with a stretching motion of an entire benzene ring that is useful to us

• The peak is often not very strong (because of a small dipole moment again), but is usually sharp and very close to 1600 cm-1, and is thus often easily identified.

•  If there is a benzene ring there should almost always also be C(sp2)-H bond vibrations, and these will be observed at >3000 cm-1

Return to Real Spectra: Example: Acetophenone

• note that you will need to be able to distinguish "real" peaks from peaks due to impurities or other artifacts, such as water as a contaminant, which is often seen as a WEAK peak around 3300 cm-1 (any “real” peaks in this region would be STRONG)

• note that a benzene ring adjacent to a C=O bond represents a common example of a the more generic conjugated C=C adjacent to C=O

Example: a hydroxy ketone

• the strong peak at 1710 cm-1 must be an aldehyde or a ketone, in this case it must be a ketone because the two C-H aldehyde peaks at ca. 2700 and ca. 2800 are not observed

• the chart below is what you are provided with on a test to help you assign peaks: