CHMBD 203 Organic Chemistry

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Fall 2007

• Molecular Formulas
• Elemental Analysis
• Molecular Mass Determination
• Molecular Formulas
• Structural inference from
• Rule of Thirteen
• Preview of HRMS

CHMBD 203 Organic Chemistry
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• 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

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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
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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
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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
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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
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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/2
1 Remember to count halogens in the number of
hydrogens and to omit oxygen
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Molecular Formulas What can be learned from
them Hydrogen Deficiency Index Lets test the
equation HDI x - y/2 z/2 1
C7H12
C5H5N
C14H10
C60
C6H12O6
C6H8O
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Molecular Formulas What can be learned from
them Hydrogen Deficiency Index Lets test the
equation HDI x - y/2 z/2 1
C7H12
C5H5N
C14H10
C60
C6H12O6
C6H8O
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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 13
13 the base formula being CnHn
r For this formula, the HDI can be calculated
from the following formula HDI ( n
r 2 ) 2
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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
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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 / 13 n r / 13 7
7 / 13 Base formula C7 H7 7
C7H14 and HDI (U) (7 7 2)/2
1 Remember, this is only the first of several
possible formulas that give a molecular mass of
98!
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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
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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 1 1
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
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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
1.5 Probably an incorrect formula, it is
unlikely this compound has nitrogen Base
formula C7H14 Add Sulfur C5H6S (sub.
C2H8) HDI 3 Very few possibilities
with only 6 hydrogens and an HDI of 3 Base
formula C7H14 Add Bromine CH7Br (sub.
C6H7) HDI -2 Impossible structure
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Molecular Formulas Where we are Importance of
Molecular Formula in Structure Determination
HDI
HDI calc.
HDI calc.
Molecular Formula
Functional group inference
Molecular Mass
Rule of 13
Now we see the experimental need to get this
information
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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.

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Mass Spectrometry
Introduction
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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.

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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.

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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.

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Mass Spectrometry
Introduction
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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 31 ratio
• Thus, there are two peaks in a 31 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 31 ratio, a Cl atom is
  present
• Br has two isotopes79Br and 81Br, in a ratio of
  11. Thus, when the molecular ion consists of
  two peaks (M and M 2) in a 11 ratio, a Br atom
  is present.

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Mass Spectrometry
Alkyl Halides and the M 2 Peak
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Mass Spectrometry
Alkyl Halides and the M 2 Peak
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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 12.0000, the masses of all
  other nuclei are very closebut not exactlywhole
  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.

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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.

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

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• 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 M1 ion
• Divide intensity of M1 by M and multiply by
  100
• Divide the result by 1.1 this gives the rough
  number of carbons
• Locate M2 ion
• If present indicates presence of silicon,
  sulfur, clorine or bromine
• If M2 is 4-5 the intensity of M sulfur or
  silicon is present

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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 200-400 nm.

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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.

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Conjugation, Resonance and Dienes
Conjugated Dienes and Ultraviolet Light

• The promotion of electrons in ? bonds and
  unconjugated ? bonds requires light having a
  wavelength of lt 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.

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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.

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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.

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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 gt 290 nm reaches the skins surface.
• Much of this UV light is absorbed by melanin, the
  highly conjugated colored pigment in the skin
  that serves as the bodys natural protection
  against the harmful effects of UV radiation.

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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.