Pharmaceuticals (2.4, 2.2, 3.2, 3.3, and 3.4)
The Bonding Triangle
Covalent Bonding
Covalent Bonding:
Electrons are shared rather than transferred
Generally bonding between non-metals is covalent and bonding between a metal and non metal is ionic
Can be be simple with a molecule structure (H2O) or can be a complex covalent structure (Graphite)
Results from a balance between the attraction between the protons and the electrons and the repulsion of the two nuclei
Why does it occur:
Everything tends to lower energy only when their is a full energy level (an octet)
H, He, Li, Be do not obey this rule as they exist with 2 electrons in their outermost energy level
Boron can exist both as 2 and 8 electrons but most stable is 6 electrons
Bond length:
The bonding electrons draw the atoms closer together but as the atoms get very close they experience repulsive forces from the other non-bonding and from the two nuclei themsleves
This means that there is a minimum distance for the two atoms which called the bond length
Generally as bond strength increases bond length decreases
Coordinates Bonds
In a normal covalent bond each atom contributes electrons equally. In a coordinate covalent bond one of the atoms contributes more electrons than the other. A common example of this is the bond in carbon monoxide.
In order for a coordinate bond to form the contributing atom must have an available lone pair of electrons.
VSEPR Model
Drawing Lewis Formulas:
Count the total number of valence electrons in the molecule. For ions add or subtract the electron
Count the total number of electrons the atoms want. H wants 2, B wants 6 and all others want 8
(Total electrons wanted)- (valence electrons)=bonding electrons
Number bonds=bonding electrons/2 (2 electrons per ‘bond’)
Arrange atoms so that each atom has teh best number of covalent bonds. The least abundant atoms is usually in the centre
Number lone electrons =(current valence electrons) - (bonding electrons)
Starting with the outer atoms add the remaining valence electrons to form lone pairs. Once the outer atoms are full then add the remaining electrons to the central atom
If the structure is an ion add square brackets and the charge at the uppermost right hand corner
Three Postulates:
i. Valence electrons are invovled in bonding
ii. Lone electrons pairs and shared electrons pairs on the central atom
iii. Lone pairs repel more than shared paris
Notice the shapes with tetrahedral electron arrangements - trigonal pyramidal has a bond angle of 107 rather than 109.5 because the lone pair repels the bonding pairs more than they repeal each other
Based on the Lewis formulas the shape of the molecule can be determined
the shape is based on the location of the nuclei in a molecule
So double and triple bonds count as one shared pair when determining the shape of the molecule
Or determine the number of electron domains ( a region where you can find the electrons)
Single bonds double bonds triple bonds and a lone pair are all considered to have a negatively charged center
Locate the bonded pairs and lone pairs on the central atom
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Resonance
Is when a molecule or an ion can have more than one drawn lewis formula
Ozone and Resonance
Bond enthalpy: is the enthalpy of change
moving of electron between two alternate structure for extra stability
Molecule Polarity
A dipole exists in a bond when the electronegativity difference is between 0.4 and 1.7
Determining molecular polarity
Draw the lewis formula
Identify polar bonds using the difference in electronegativity
a. if there are no polar bonds then the molecule is non polar (depends on the lone pairs
use VSEPR to figure out the shape of the molecule
a. If the molecule is completely symmetrical the polar bonds can cancel each other out making the molecule non polar.
Covalent network structures
Diamond
Giant 3D covalent structure each carbon is bonded to four other carbons in a tetrahedral shape
sp3
Graphite:
Giant 2D covalent structure
Has delocalized electrons so can transfer electron
sp2
Fullerenes:
C60 composed of 5 tor 6 carbon rings
Exactly the same as graphite except a single sheet
sp2
Intermolecular Forces
Metallic:
Al>Mg>Na
Because same #energy levels but increasing proton number thus decrease in ionic radii and increase in metallic bonding also more delocalized electrons
Break covalent=high energy
giant covalent
Ionic compounds
The attraction between the ions is an electron static attraction and seen as an intramolecular forces
Polar covalent molecules
Intermolecular forces will be mainly dipole dipole and may be hydrogen if the hydrogen in the molecule is bonded to a very electronegative oxygen, nitrogen or fluorine
Non Polar Covalent Molecules
Intermolecular forces only London Dispersion Forces
London dispersion forces result from a temporarilty induced dipole
Uneven movement of electrons canresult in a bunch of electrons located on one side of the molecule which gives that side of teh molecule a slightly negative charge. A molecule near it will have a positive charge induced on it
Benzene
Alternating three single bonds and three double bonds
What are three pieces of evidence that prove benzene has a ring structure?
Does not undergo electrophilic addition reactions
Bond strength is the same
The bond length is the same
Due to extra bond strength and bond length extra stability
Expanded Octets
Atoms in the 3rd period have d-orbitals available, which allows them to form more bonds than the octet rule predicts
Lewis Structures
The same rule apply, except that the central atom will have more bonds than you would thought it was allowed to have
Formal Charge
Key is to make formal charges as small as possible, that is the most likely structure
Sigma and Pi bonds
Sigma bond:
Formed by the direct overlap of orbitals
Backbone of every molecule, every covalent bond has a sigma bond
Pi bonds:
Sidewise overlap unhybridized orbitals
These form the double or triple bonds
Double bond 1σ and 1π
Triple bond 1σ and 2π bonds
Less strong because farther away from the nuclei
Hybridisation
Hybridisation:
When an atom forms a bond the s and p orbitals mix to form hybrid orbitals.
Stereoisomerism
Stereoisomers are molecules with the same structural formula but their atoms have different positions in space. They are not structural isomers
Structural isomerism:
Same molecular formula but different structural formula
Stereoisomers are divided in two classes conformation isomers and configurational isomers
Only configurational isomers need to be learnt
Configurational isomers:
cis trans and E/Z isomers position about a carbon double bond
optical isomerism about a chiral carbon center
Can only change by breaking bonds, inter convert
Cis-Trans Nomenclature
Cis-trans isomers are also known as geometric isomers.
Cis-trans isomerism occurs in molecules with a carbon double bond
two different groups attached to each carbon in the carbon-carbon bond
the double bond prevents rotation
Cis isomer:
similar parts are on the same side
trans isomer:
similar parts are on different sides
Optical isomers:
Optical isomers have chiral centres - element attached to four different substituent groups
Optical isomers come in pairs they are mirror images of each other
Optical isomers rotate plane polarized light otherwise have the same chemical and physical properties
Both isomers rotate the same amount of light but in different directions
Chiral centre:
Carbons with two or three hydrogen atoms attached to them are not chiral centres
Carbons with a double bonded oxygen atom cannot be chiral centres
A molecule can have more than one chiral centre ( called a diasteromers)
Optical isomers come in pairs
With structural isomers there can be more than two for the same chemical formula
With optical isomers - there are only two per chiral carbon and they are called enantiomers
Optical Activity:
Stereoisomers are said to be optically active if they rotate plane polarized light
Polarized light: light waves vibrating in only one plane. Usually light waves are vibrating in all planes
Each type of enantiomer rotates light the same amount, but in different directions
Amount and angle of rotation must be experimentally determined using a polarimeter
The amount of rotation depends on
length of sample tube
concentration of enantiomers
Both isomers present rotation cancels out called racemic mixture
enantiomers can be isolated from a racemic mixture through resolution.
Diasteromers:
Diastereomers contain two or more chiral centres. They are non imposable but do not form mirror images. Diastereomers have different physical and chemical properties
Mass spectrometry
When a molecule is vaporized and then ionised in a mass spectrometer it form the molecular ion M+.
This gives the molecular mass but the molecule can also fragment in to smaller ions if the electron hits a bond. A mass spectrum can be analyzed to see the differences in molecular ion peaks and therefore identify the parts of a molecule. The peaks from the fragments are known as a mass spectrum.
Some fragments ions are not stable enough to pass through the mass spectrometer so mass spectrums do not represent all components of the molecule
Infrared spectra
Covalent bonds behave like springs and vibrate at a particular frequency that depends on the nature of the bond and the type of vibration, stretching or bending. The energy of these vibrations corresponds to the infrared region of the electromagnetic spectrum. When IR with a frequency equal to the natural frequency of the vibration of the bond in a molecule the IR is amplified. The model used in IR spectroscopy is known as the spring model.
IR numbers are reciprocals of wavelength (1/λ). They are also referred to as wavenumbers and measured in cm-1
The relationship between bond strength and the amount of IR absorbed can be seen through the use of Hook’s law
The relationship between bond strength and the amount of IR absorbed can be seen through the use of Hooke’s law
Lighter atoms will vibrate at higher frequencies and heavier atoms at lower frequencies.
In order for a covalent bond to absorb infrared radiation there must be change in the dipole moment. Diatomic molecules containing only one element eg H2 do not absorb infrared radiation
IR spectrums can be used to identify functional groups. Table 20 of the data booklet shows the areas on a spectrum that are related to specific organic molecules
The absorbance, A, of a sample is directly related to %transmittance. Low% transmission indicates high absorption
Proton nuclear magnetic resonance spectroscopy
Proton Nuclear Magnetic resonance, or 1H NMR, gives information on the chemical environment of all the hydrogens in a molecule. The nuclei of hydrogen atoms possess spin and can exist in two states of equal energy.
If a strong magnetic field is applied, the spin states will align either with or against the magnetic field, and there is a small energy difference between them. The nuclei absorb energy when transferring from the lower to higher spin state. The energy difference is small and corresponds to the radio wave region of the electromagnetic spectrum. The precise energy difference depends on the chemical environment of the hydrogen atoms.
The H NMR spectrum of an organic compound provides information concerning:
the # of different types of hydrogens present in the molecule
the relative #’s of the different types of hydrogens
the electronic environment of the different types of hydrogens
the number of hydrogen “neighbor”’ a hydrogen has
Ethyl acetate contains 8 hydrogens and some of them are different from each other
Three hydrogens are attached to a carbon bonded to a carbonyl group and are different from the hydrogens bonded to a carbon attached to an oxygen atom.
Every chemically different hydrogen or group of hydrogens will give a peak in the NMR spectra. The position in the spectrum where peak occurs for each hydrogen is known as the chemical shift from a known reference and is measured in parts per million (ppm). TMS, the reference, is assigned as 0ppm
1H NMR spectrum also contain an integrated trace that shows the proportional number of hydrogen atoms present. An integration trace measures the relative areas under the various peaks in the spectrum. When the integration trace crosses a peak or group of peaks, it gains height. The height gained is proportional to the hydrogens under the peak or group of peaks.
Water molecules can be detected in human cells due to the protons (hydrogens) that water contains Magnetic Resonance Imaging uses HNMR spectroscopy to give a three dimensional representation of the organs in the human body
High resolution 1H NMR Spectroscopoy
Splitting patterns are due to spin-spin coupling. If there is one hydrogen proton (n=1)next to a methyl group then it will either line up with the magnetic field or be aligned against it. This results in the methyl protons experiencing a slightly stronger and a slightly weaker external magnetic field, known as a doublet
If there is a -CH2 group (n=2) adjacent ot a methylg roups then there are three possible energy states available when an external magnetic field is applied.
Both proton spins are aligned wit hthe field
One is aligned with the field and one against (two combinations
Both are aligned against the field
This results in a split whose peaks are in ration 1:2:1
Pascal’s triangle can be used to predict the splitting pattern based on all possible combinations
TMS as a reference
In H NMR the peaks are not associated with a wavelength or frequency. The intensity of the peaks depends on the strength of the external magnetic.
Magnets vary so peak height also varies. To sove this problem a universel reference solution of TMS, tetramethysilane, is used.
Tetramethylsilane, Si(CH3)4 is used as a standard as it has the following advantages
All the 12 protons are in the same chemical environment so it gives a strong single peak
It’s not toxic and is unreactive
It absorbs upfield, well away from most other protons
Is volatile and can be easily removed from the sample
Interpreting H NMR spectrums
There are two main rules used in interpreting HNMR spectrums
Rule 1 number of shifts (peak groups) not counting TMS (at 0) represent the number of hydrogen environments
Rule 2: The number of lines (splitting per shift can be used to determine the number of hydrogens in adjacent groups
Integration: measures the area under each peak to reveal the relative number of equivalent hydrogen atoms (protons) in each chemical environment
Reduction of carboxylic acids
Carboxylic acids can be reduced to primary alcohols (via the aldeyde)
Ketones can be reduced to secondary alcohols
Typical reducing agents are lithium aluminum hydride (LiAlH4) in dry ether (used to reduce carboxylic acids) and sodium (NaBH4)
The reducing agent (LiAlH4) provides hydrogen in two forms H+and H-
H- acts as a nucleophile (nucleus/protons seeking)
The H+ is the attacking species
Lithium Aluminium Hydride is dissolved in dry ether so that water does not contribute OH- to the reaction
Reduction of alkenes and alkynes
Alkenes and Alkynes are unsaturated compounds. The double and triple bond is more reactive than the single bond so both alkenes and alkynes undergo addition reactions
Alkene reaction 1: Halogenation
Reagants: Halogen
Conditions: can occur at room temperature
Alkane + halogen → Halogenoalkane + Halogen halide
Bromine is used to test for the presence of doulbe bonds (alkane vs alkene). Iodine is used to determine the unsaturation of fats. Both these reactions are examples of halogenation
Alkene reaction 2: Hydrohalogenation
Alkene +hydrogen halide → Halogenoalkane
Reagents: hydrogen halide
Conditions: Can occur at room temperature
Reaction 3: Hydration
Alkene +water → Alcohol
Reagents: water
Conditions: conc H3PO4 heat (300°C)/60 room temperature
Reaction 4: hydrogenation
Alkene +hydrogen → Alkane
Reagents: hydrogen
Conditions: Nickel catalyst, heat
Reaction 5: Addition polymerisation
Alkene + (many)Alkenes → Polyalkene
Reagents: Alkene monomers
Conditions: High pressure, heat, catalyst (depending on the polymer)
Reaction 6: Hydrolysis of Halogenoalkanes
Halogenoalkane + water → Alcohol + Hydrogen halide
Reagents: Aqueous NaOH or KOH
Conditions: Heat under reflux
Reaction 7: Oxidation of Alcohols → Aldehydes
Primary alcohol + oxygen → Aldehyde + water
Reagents: Acidified potassium dichromate(VI), K₂Cr₂O₇/H⁺
Conditions: Heat gently and distil the aldehyde as it forms
Important: Distillation is used so the aldehyde is removed before it can be further oxidised.
Reaction 8: Oxidation of Aldehydes → Carboxylic Acids
Aldehyde + oxygen → Carboxylic acid
Reagents: Acidified potassium dichromate(VI), K₂Cr₂O₇/H⁺
Conditions: Heat under reflux
Important: Reflux allows the aldehyde to be oxidised further to the carboxylic acid.
Reaction 9: Dehydration of alcahols
Alcohol → Alkene
Reagents: H2SO4
Conditions: High temperature
Curly arrows
A curly arrow is used to show the direction of electrons within bonds, drawn from the site of elcetron availability, such as a pair of lone electrons, to the site of electron deficiency, such as an atom with a partial positive charge
Using curly arrows to show the movement of electrons
The arrow tail is where the electron pairs starts from. That’s always fairly obvious but you must remember that a lone pair is a pair of electrons at the bonding level which isn’t being used to attach on to anything else.
The arrow head is where you want the electron pair to end up
For example, in the reaction between ethene and hydrogen bromide, one of the two bonds between the two carbon atoms breaks. That bond is simply a pair of electrons.
Those electrons move to form a new bond with the hydrogen from the HBr. At the same time the pair of electrons in the hydrogen-bromine bond moves down onto the bromine atom.
The second stage of this reaction illustrates how you use a curly arrow if a lone pair of electrons is involved
The first stage leaves you with a slightly positive charge on the right hand carbon atom and a bormide ion. You can think of hte elcetrons shown on the bromide ion as being the ones which orriginally made up the hydrogen bromide bond.
The lone pair on the bromide ion moves to form a new bond between the bromide and the slightly positive carbon aotm. That movement is again shown by a curly arrow. The curly arrow poitns towards the carbon and the bromide because thats where the electron pairs ends up.
That leaves you with the product of this reaction 1-bromoethane
Free Radical Mechanism
Alkanes are not very reactive due to strong single bonds. To substitute the hydrogen when another group a mechanism is required.
Alkanes become halogenoalkanes through the free radical mechanism.
Free radicals are formed through homolytic fission.
A-B → A + B
(heat or light)
Chain initation
The first step is initiated by UV light breaking a halogen molcue into free radicals
Half (fish hook) arrows are sued to show the movement of a single electron
Invovle the reaction betwen one free radical and one normal molecule to produce another free radical and one normal molecule
Chain termination reactions
Are reactions which remove free radicals
Two free radicals react together to form a normal molecule
Chain propagation reactions
Invovle the reaction between one free radical and one normal molecule to produce another free radical and one normal molecule
Chain termination reactions
Are reactions which remove free radicals
Two free radicals react together to form a normal molecule