1. CHEM 203 – Organic Chemistry
Fall 2017
Molecular Formulas
Elemental Analysis
Molecular Mass Determination
Structural inference from
Rule of Thirteen
Preview of HRMS
CHEM 203 – Organic Chemistry

2. Molecular Formulas – What can be learned from them
Importance:
Organic molecules exist as discrete sets of covalent bonds based on the valence of the elements that comprise them
i.e. hydrogen is monovalent, oxygen divalent and carbon tetravalent…
If a molecular formula is known:
Functional groups can be implied or ruled out
Obvious, but often overlooked tool
The number of times valence rules for elements are violated is implied
Most commonly for carbon, which is called the index of unsaturation or hydrogen deficiency index (HDI), less commonly for elements such as oxygen and nitrogen that may be involved in acid-base chemistry

3. Molecular Formulas – What can be learned from them
Hydrogen Deficiency Index
For simple straight chain or branched hydrocarbons, there is always a certain ratio of hydrogen to carbon necessary to make the entire structure saturated:
We say these molecules are not hydrogen deficient, and set the index at zero

4. Molecular Formulas – What can be learned from them
Hydrogen Deficiency Index
If we add a double bond anywhere in the structure, two hydrogens must be removed for each double bond
We say these molecules are hydrogen deficient, and the index increases by one for each double bond added, for the first structure, the index is one, for the second the index is two

5. Molecular Formulas – What can be learned from them
Hydrogen Deficiency Index
A ring closure, like a double bond requires the “sacrifice” of two hydrogens from the formula, increasing the index by one for each closed ring in the compound
Triple bonds act as two double bonds increasing the index by two for each one in a molecule
Hence, the first structure has an index of one, the second an index of two

6. Molecular Formulas – What can be learned from them
Hydrogen Deficiency Index– other elements
Nitrogen is usually assumed to be trivalent; obviously ammonium salts and nitro compounds violate this.
Assume nitrogen is trivalent, and therefore, for every nitrogen in a structure, one less hydrogen is needed to “fill” its valence requirement than carbon
Halogens (normally monovalent) merely replace hydrogen in a like-indexed formula

7. Molecular Formulas – What can be learned from them
Hydrogen Deficiency Index– the equation!
Elements such as carbon and hydrogen never violate their index rules
Elements such as oxygen rarely violate their index rules
Elements such as nitrogen and the halogens may violate their index rules
Higher elements, found commonly in biologically interesting organic compounds, such as sulfur and phosphorus exist in almost equal populations in the various valences they are capable of and are typically not considered by this method directly
Furthermore, it is tedious to go through a structural analysis to get the index of unsaturation. It can be algebraically expressed by combining the effects of each of the common elements.
For an organic compound of formula CxHyNzO the index of hydrogen deficiency becomes:
HDI = x - y/2 + z/
Remember to count halogens in the number of hydrogens and to omit oxygen

8. Molecular Formulas – What can be learned from them
Hydrogen Deficiency Index
Let’s test the equation:
HDI = x - y/2 + z/
C7H12
C5H5N
C14H10
C60
C6H12O6
C6H8O

9. Molecular Formulas – What can be learned from them
Hydrogen Deficiency Index
Let’s test the equation:
HDI = x - y/2 + z/
C7H12
C5H5N
C14H10
C60
C6H12O6
C6H8O

10. Molecular Formulas – What can be learned from them
The Rule of Thirteen – Molecular Formulas from Molecular Mass
For the formula “connoisseur” there is another algebraic treatment of molecular mass that can lead to possible molecular formulas
When a molecular mass, M, is known, a base formula can be generated from the following equation:
M = n r
the base formula being: CnHn + r
For this formula, the HDI can be calculated from the following formula:
HDI = ( n – r + 2 ) 2

11. Molecular Formulas – What can be learned from them
The Rule of Thirteen
When a formula containing other elements than carbon and hydrogen are considered, the appropriate adjustment must be made.
If we wish to consider that the base formula also includes oxygen, with atomic mass 16, one carbon (12) and four hydrogens (4 x 1) must be removed to give the same molecular mass
Likewise, an adjustment to hydrogen deficiency must be made. The following table gives the carbon-hydrogen equivalents and change in HDI for elements also commonly found in organic compounds:
Element added
Subtract:
D HDI
(DU in text) C
H12 7
35Cl
C2H11 3 -7
79Br
C6H7 -3 O
CH4 1 F
CH7 2 N
CH2
1/2 Si
C2H4 S
C2H8 P
C2H7 I
C9H19

12. Molecular Formulas – What can be learned from them
The Rule of Thirteen
Possible molecular weights can only generate real formulas; if the assumption you made is incorrect fractional elements or HDI indices appear, or sub-zero HDI.
Some examples:
We experimentally determine the molecular mass to be 98
From the rule of thirteen a base formula is generated:
98 / = n r / 13
= / 13
Base formula = C7 H = C7H14
and HDI (U) = (7 – 7 + 2)/2 =
Remember, this is only the first of several possible formulas that give a molecular mass of 98!

13. Molecular Formulas – What can be learned from them
The Rule of Thirteen
From this starting point, we can infer the isomeric alkenes (HDI = 1) of molecular formula C7H14:
Or we can infer the various aliphatic ring compounds, C7H14:
Observe how, with the knowledge of molecular mass, we can whittle the infinity of possible organic compounds to two families of closely related isomers, and even begin to know something about the chemistry of the unknown
Remember, off of the base formula we can begin to add other elements to see what other possibilities give a molecular mass of 98…

14. Molecular Formulas – What can be learned from them
The Rule of Thirteen
If we now assume the unknown has a single oxygen:
Base formula: C7H14
Add oxygen: C7H14O (mol. mass now 114)
Subtract CH4: C6H10O (mol. mass now correct at 98)
HDI correction: = 2 (originally 1, add one for O)
(you can check the HDI vs. the new formula as well)
We can now picture compounds that have the formula C6H10O with a HDI of 2:
Quickly, we can add other elements, such as nitrogen, halogen and sulfur. See how for a low molecular mass the inference of big elements greatly simplifies the number of possible structures

15. Molecular Formulas – What can be learned from them
The Rule of Thirteen
Quickly, we can add other elements, such as nitrogen, halogen and sulfur. See how for a low molecular mass the inference of big elements greatly simplifies the number of possible structures:
Base formula: C7H14
Add Nitrogen: C6H12N (sub. CH2)
HDI:
Probably an incorrect formula, it is unlikely this compound has nitrogen
Add Sulfur: C5H6S (sub. C2H8)
HDI:
Very few possibilities with only 6 hydrogens and an HDI of 3
Add Bromine: CH7Br (sub. C6H7)
HDI:
Impossible structure

16. Molecular Formulas – Where we are
Importance of Molecular Formula in Structure Determination
HDI
HDI calc.
HDI calc.
Molecular
Formula
Molecular
Mass
Functional
group
inference
Rule of 13
Now we see the experimental need to get this information

17. Mass Spectrometry Introduction
Mass spectrometry is a technique used for measuring the molecular weight and determining the molecular formula of an organic compound.
In a mass spectrometer, a molecule is vaporized and ionized by bombardment with a beam of high-energy electrons.
The energy of the electrons is ~ 1600 kcal (or 70 eV).
Since it takes ~100 kcal of energy to cleave a typical s bond, 1600 kcal is an enormous amount of energy to come into contact with a molecule.
The electron beam ionizes the molecule by causing it to eject an electron.

18. Mass Spectrometry
Introduction

19. Mass Spectrometry Introduction
When the electron beam ionizes the molecule, the species that is formed is called a radical cation, and symbolized as M+•
The radical cation M+• is called the molecular ion or parent ion.
The mass of M+• represents the molecular weight of M
Because M is unstable, it decomposes to form fragments of radicals and cations that have a lower molecular weight than M+•
The mass spectrometer analyzes the masses of cations
A mass spectrum is a plot of the amount of each cation (its relative abundance) versus its mass to charge ratio (m/z, where m is mass, and z is charge)
Since z is almost always +1, m/z actually measures the mass (m) of the individual ions.

20. Mass Spectrometry Introduction
Consider the mass spectrum of CH4 below:
The tallest peak in the mass spectrum is called the base peak
The base peak is also the M peak, although this may not always be the case
Though most C atoms have an atomic mass of 12, 1.1% have a mass of 13. Thus, 13CH4 is responsible for the peak at m/z = 17. This is called the M + 1 peak.

21. Mass Spectrometry Introduction
The mass spectrum of CH4 consists of more peaks than just the M peak
Since the molecular ion is unstable, it fragments into other cations and radical cations containing one, two, three, or four fewer hydrogen atoms than methane itself
Thus, the peaks at m/z 15, 14, 13 and 12 are due to these lower molecular weight fragments.

22. Mass Spectrometry
Introduction

23. Mass Spectrometry Alkyl Halides and the M + 2 Peak
Most elements have one major isotope.
Chlorine has two common isotopes, 35Cl and 37Cl, which occur naturally in a 3:1 ratio
Thus, there are two peaks in a 3:1 ratio for the molecular ion of an alkyl chloride
The larger peak, the M peak, corresponds to the compound containing the 35Cl. The smaller peak, the M + 2 peak, corresponds to the compound containing 37Cl
Thus, when the molecular ion consists of two peaks (M and M + 2) in a 3:1 ratio, a Cl atom is present
Br has two isotopes—79Br and 81Br, in a ratio of ~1:1. Thus, when the molecular ion consists of two peaks (M and M + 2) in a 1:1 ratio, a Br atom is present.

24. Mass Spectrometry
Alkyl Halides and the M + 2 Peak

25. Mass Spectrometry
Alkyl Halides and the M + 2 Peak

26. Mass Spectrometry High Resolution Mass Spectrometers
Low resolution mass spectrometers report m/z values to the nearest whole number. Thus, the mass of a given molecular ion can correspond to many different masses
High resolution mass spectrometers measure m/z ratios to four (or more) decimal places.
This is valuable because except for 12C whose mass is defined as , the masses of all other nuclei are very close—but not exactly—whole numbers
Table 14.1 lists the exact mass values for a few common nuclei. Using these values it is possible to determine the single molecular formula that gives rise to a molecular ion.

27. Mass Spectrometry High-Resolution Mass Spectrometers
Consider a compound having a molecular ion at m/z = 60 using a low-resolution mass spectrometer. The molecule could have any one of the following molecular formulas.

28. Mass Spectrometry
Gas Chromatography-Mass Spectrometry (GC-MS)

29. Mass Spectrometry Gas Chromatography-Mass Spectrometry (GC-MS)
To analyze a urine sample for tetrahydrocannabinol, (THC) the principle psychoactive component of marijuana, the organic compounds are extracted from urine, purified, concentrated and injected into the GC-MS
THC appears as a GC peak, and gives a molecular ion at 314, its molecular weight

30. Wrapping it up – what can be done with mass spectra?
Most powerful tool for determining molecular mass of small compounds
Locate M+ ion
Gives molecular mass
If odd there is 1,3,5… nitrogens in compound
If even there are 0,2,4… nitrogens in compound
If large – aromatic ring is probably present
If small or not-existent – alcohol, amine
Use the rule of thirteen to generate possible molecular formulas
Locate M+1 ion
Divide intensity of M+1 by M+ and multiply by 100%
Divide the result by 1.1 – this gives the rough number of carbons
Locate M+2 ion
If present indicates presence of silicon, sulfur, clorine or bromine
If M+2 is ~4-5% the intensity of M+ sulfur or silicon is present
If M+2 is 33% the intensity of M+ there is a chlorine present
If M+2 is equal in intensity to M+ there is a bromine present

31. Conjugation, Resonance and Dienes
Conjugated Dienes and Ultraviolet Light
The absorption of ultraviolet (UV) light by a molecule can promote an electron from a lower electronic state to a higher one.
Ultraviolet light has a slightly shorter wavelength (and thus higher frequency) than visible light.
The most useful region of UV light for this purpose is nm.

32. Conjugation, Resonance and Dienes
Conjugated Dienes and Ultraviolet Light
When electrons in a lower energy state (the ground state) absorb light having the appropriate energy, an electron is promoted to a higher electronic state (excited state).
The energy difference between the two states depends on the location of the electron.

33. Conjugation, Resonance and Dienes
Conjugated Dienes and Ultraviolet Light
The promotion of electrons in  bonds and unconjugated  bonds requires light having a wavelength of < 200 nm; that is, a shorter wavelength and higher energy than light in the UV region of the electromagnetic spectrum.
With conjugated dienes, the energy difference between the ground and excited states decreases, so longer wavelengths of light can be used to promote electrons.
The wavelength of UV light absorbed by a compound is often referred to as its max.

34. Conjugation, Resonance and Dienes
Conjugated Dienes and Ultraviolet Light
As the number of conjugated  bonds increases, the energy difference between the ground and excited state decreases, shifting the absorption to longer wavelengths.
With molecules having eight or more conjugated  bonds, the absorption shifts from the UV to the visible region, and the compound takes on the color of the light it does not absorb.

35. Conjugation, Resonance and Dienes
Conjugated Dienes and Ultraviolet Light
Lycopene absorbs visible light at max = 470 nm, in the blue-green region of the visible spectrum. Because it does not absorb light in the red region, lycopene appears bright red.

36. Conjugation, Resonance and Dienes
Sunscreens
UV radiation from the sun is high enough in energy to cleave bonds, forming radicals that can prematurely age skin and cause cancer.
However, since much of this radiation is filtered out by the ozone layer, only UV light having wavelengths > 290 nm reaches the skin’s surface.
Much of this UV light is absorbed by melanin, the highly conjugated colored pigment in the skin that serves as the body’s natural protection against the harmful effects of UV radiation.

37. Conjugation, Resonance and Dienes
Sunscreens
Prolonged exposure to the sun can allow more UV radiation to reach your skin than melanin can absorb.
Commercial sunscreens can offer some protection, because they contain conjugated compounds that absorb UV light, thus shielding the skin (for a time) from the harmful effects of UV radiation.
Commercial sunscreens are given an SPF rating (sun protection factor), according to the amount of sunscreen present. The higher the number, the greater the protection.
Two sunscreens that have been used for this purpose are para-aminobenzoic acid (PABA) and padimate O.