Organic Chemistry Notes

Organic Chemistry – Chemistry 1Weeks 1, 2, 3 & 4

Lecture 1

Chemistry: What is it good for? To understand the properties of all matter To understand the interactions of materials To understand biological processes To develop new drugs (antibiotics, anti-cancer agents...) To develop new materials (plastics, ceramics...)

The first synthetic chemists (making new molecules) 1828; Wohler prepares urea

1857; Perkin makes mauveine from coal tar

Chemical Bonds and StructureIn addressing the properties of different compounds it is useful to group them into two classes:

Ionic Compounds Complete transfer of one or more electrons occurs, creating ions.

Ions are held together (in a lattice) by strongelectrostactic forces

Covalent Compounds Bonding electrons are shared between atoms Overlap of electronic orbitals gives rise to bonding orbitals, or covalent bonds

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What are covalent bonds? Two electrons shared between two atoms

Electronic Configuration Describes the orbitals occupied by electrons for a given element

Orbital Theory The space around a nucleus in which an electron is most likely to be residing is

termed an orbital

What does an orbital look like? The

further from the nucleus, the higher the energy of the orbital

The shape of an

orbital varies with type

Electronic Configuration Energy levels of orbitals...

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Lecture 2

Formation of covalent bonds A covalent bond is formed by the sharing between atoms of unpaired electrons Unpaired electrons are always in the outer (valence) shell highest energy occupied

orbitals Two theories used to describe covalent bond formation;

o Valence bond theoryo Molecular orbital theory

Valence bond theory

Overlap of two singly-occupied orbitals gives a bonding orbital

Bonds formed by head-on overlap of orbitals are -bondsσ

Molecular orbital theory Comb

ination of 2

atomic orbitals gives 2 molecular orbitals Additive combination gives bonding

molecular orbital (filled, low energy) subtractive conbinaition gives anti-bonding

molecular orbital (not filled, high energy)

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Formation of covalent bonds A covalent bond is formed by the sharing between atoms of unpaired outer shell

electrons

Lewis structures A simple way of representing covalent bonds is by Lewis structures;

o valence electrons are represented by dotso a stable molecule exists when an inert gas configuration is achieved for all

atoms (stable octet rule)

methane methanol

Orbital theory and carbon? The ground state configuration of carbon contains only two unpaired electrons Yet carbon forms four covalent bonds to achieve a stable octet

Carbon: 1s2 2s2 2p2

methane, CH4

Excited state configuration

ground state excited state

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Carbon: 1s2 2s2 2p2 Carbon: 1s2 2s1 2p3 two unpaired valence electrons four unpaired valence electrons

Bonding in carbon But…

o Bonding in this state would give 3 equivalent bonds (from the 2p orbitals) and 1 different bond (from the 2s orbital).

o How do we account forsame length and strength?

HybridisationThe 2s, 2px, 2py, &2pz orbitals are hybridised to

generate four equivalent sp3 orbitals

Carbon: 1s2 2s1 2p3 Carbon: 1s2 [2sp3]4 state excited possible bonding state

The four sp3orbitals have a tetrahedral arrangement around the nucleus This can be determined mathematically (Schroedinger equation), and/or can be

thought of as the arrangement that places the four orbitals as far apart as possible (VSEPR theory).

Tetrahedral geometry Methane, CH4 Ethane, C2H6 Oxygen and nitrogen can also be sp3-

hybridised;

Representation of molecules Lewis structure;

o confusing even with small molecules

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Kekule structure (Structural formula);o covalent bonds represented as lineso cumbersome for larger molecules

Condensed structural formula;

Line structure;o C-C bonds drawn as lineso C-H bonds omittedo non-C,H atoms drawno only H s not bonded to C shown

Alkanes

e.g. octane

Structural isomers Alkanes with four or more carbons can exist as structural isomers Structural isomers have the same molecular formula, but have different bond

connectivity

Structural isomers may have different physical and chemical properties

C6H14

C9H8O4

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aspirin and acetozone are structural isomers with different chemical properties

it is not possible to derive molecular structures from their trivial names systematic names are required

Nomenclature - the rules

Identify the longest carbon chain (parent chain) Identify the substituent(s) Number the longest chain to give the lowest possible numbering for the

substituent(s) Allocate a number to every substituent List substituents in alphabetical order Identical substituents are indicated by prefixes: di (2), tri (3), tetra (4)

Isomers of hexane

a more complicated example...

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2-methylpentane

3-methylpentane

2,3-dimethylbutane

2,2-dimethylbutane

Functional groupsOrganic molecules may incorporate functional groups…

Alcohol OH CH3CH2OH (ethanol)Halide F,Cl,Br,I CH3I (iodomethane)Carboxylic acid CO2H CH3CO2H (ethanoic acid)Amine NH2 CH3CH2NH2 (ethylamine)

Conformational isomers There is free rotation about a -bondan infinite array of conformations is possibleσ

through rotation a conformer is one specific conformation of a molecule different conformers are isomers - they differ by the arrangement of atoms in space

Newman Projection Conformational isomers are easily distinguished in a Newman projection (looking

directly down a carbon-carbon bond)

Staggered vs Eclipsed

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4-ethyl-2,2,6,8-tetramethylnonanenot

6-ethyl-2,4,8,8-tetramethylnonane2,2,6,8-tetramethyl-4-ethylnonane


Staggered conformers are more stable (lower in energy) than eclipsed conformers, due to reduces steric interactions

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Lecture 3

Conformers of butane

Conformation of long-chain alkanes The most stable conformer of long-chain alkanes is when all anti-staggered

conformations are adopted, leading to a characteristic zig-zag or sawtooth structure.

Lipids Phospholipids are principle components of cell membranes (lipid bilayer) Contain long alkane chains that stack together Polar groups exposed to aqueous environment

Cycloalkanes Cycloalkanes have a cyclic structure, and general formula CnH2n Named by including cyclo prefix

Cyclopropane Cyclohexane

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Cyclopropane is highly strained, with both unfavourable bond angles, and unfavourable eclipsing interactions

6-membered rings are strain free, with all C-C-C angles close to the optimal 109.5 for tetrahedral geometry, and an all staggered arrangement

This is possible by adopting a chair conformation

Cyclopentane Cyclohexane

Cyclohexane chair conformation The chair conformation results in two types of hydrogen environments; axial and

equatorial

Ring Flipping Two chair conformations exist which interconvert by ring-flipping

Ring-flipping interchanges axial and equatorial substituents

Substituted cyclohexanes Equatorial substituents result

in more stable conformation due to decreased steric interactions

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Disubstitued cycloalkanes Rings prevent free rotation around single bonds Isomers can exist when two or more substituents are attached. The isomers do not interconvert (would require breaking of C-C bonds). These isomers are stereoisomers - they differ by the arrangement of atoms in space Also called cis/trans isomers, diastereomers

Cycloalkanes

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Lecture 4

Stereochemistry Tetrahedral carbons with 2 or 3 groups are identical to their mirror images A tetrahedral carbon with 4 different groups is NOT superimposable on its mirror

image These non-superimposable mirror images are therefore different substances;i.e.

they are isomers

Steoeoisomers Molecules that are non-super

imposable mirror-image are a subclass of stereoisomers (same bond connectivity but differ in the arrangement of atoms in space)

Specifically they are enantiomers

Chirality (handedness) Molecules that possess non-superimposable mirror images are said to be chiral

(from the Greek cheir ; hand ) How can we determine if a molecule is chiral?

o It must not contain a plane of symmetry A tetrahedral carbon with 4 different groups has no plane of symmetry; such a

carbon atom represents an asymmetric centre or stereogenic centre

Terminology A molecule is chiral if it is not superimposable upon its mirror image (which is true

if it does not contain a plane of symmetry). The two non-identical mirror image compounds are called enantiomers. With a few important exceptions, enantiomers have identical physical and chemical

properties. Molecules with one asymmetric/stereogenic centre (an sp3-hybridised carbon with

four different groups attached) are always chiral and exist in enantiomeric forms.

An example: lactic acid Lactic acid posesses one asymmetric centre and therefore two stereoisomers

(enantiomers) exist

Enantiomers The two ways enantimers can be

differentiated;o Enantiomers differ in the

way in which they interact with other chiral molecules

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o Enantiomers differ in the way in which they interact with plane polarised light

Rotation of plane polarised light All chiral compounds rotate the plane of polarised light to some extent - this is why

they are referred to as being optically active. A sample of one enantiomer rotates the plane of polarised light with the same

magnitude but in the opposite direction to the other enantiomer.

Absolute stereochemistry The (+)- and (-)- description of enantiomers is an observable physical property, but

does not give information about the configuration of the asymmetric centres The Cahn-Ingold-Prelog rules allow the description of the specific configuration of

asymmetric centres; (R)- and (S)-descriptors

(R)- and (S)- descriptors An asymmetric centre is described as being of the (R)- or (S)-configuration by;

o Ranking the four substituents (priorities 1–4)o Determining a clockwise or anticlockwise sequenceo Assigning (R) or (S)

Cahn-Ingold-Prelog rules Rule 1:

o Prioritise substituents in decreasing order of the atomic number of the atom directly attaches

Rule 2:o If two directly attached atoms are the same,

compare the second atoms in each group Rule 3:

o Treat multiple bonds as the equivalent number of single bonds

Rule 4:

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o View the molecule so that you are looking down the bond from carbon to group 4

anticlockwise ⇒(S)-configuration

clockwise ⇒(R)-configuration

Examples of assigning (R)- and (S)-4 pointing away1-2-3 anticlockwise⇒ (S)-configuration

(S)lactic acid

4 pointing away1-2-3 clockwise⇒ (R)-configuration

(R)glyceraldehyde

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Lecture 5

The Thumb Rule

Assigning (R)- and (S)- If the lowest priority substituent is pointing out of the page: Rotate the molecule so that it is pointing into the page, then apply the rules as

normal Reverse the anticlockwise/clockwise rule Use the thumb rule

More Terminology… An equal misture of enantiomers is termed a racemic mixture It can be difficult to separate enantiomers from a racemic mixutre as they have the

same physical and chemical properties (m.p., b.p., solubility, reactivity)

Chiral Drugs

Only the (S)-enantiomer of dopa is converted to dopamine A dangerous build-up of the (R)-enantiomer occurs if the racemic drug is given

Sedative / anti-nauseaused in late1950s/early 60s to treat morning-sickness

teratogen:causes birth defects (stunted growth of fetal limbs)

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Lecture 6

More than one asymmetric centre Each asymmetric centre has two possible configurations (R or S) A molecule with n asymmetric centres has (a maximum of) 2n stereoisomers

Diastereomers All asymmetric centres of opposite configuration

⇒ enantiomers At least one asymmetric centre of the same configuration, at least one opposite

⇒ diastereomers

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what is the relationship between these molecules?(stereoisomers that are not enantiomers)

diastereomers

Alkenes Alkenes have the general formula CnH2n

Geometry Contains C=C bond Planar arrangement of atoms Geometry of carbons is trional planar C=C bond length 1.33 Å (c.f. 1.54 for C-

C) C=C bond strength 640 kJ.mol-1 (c.f.

360 for C-C)

Hybridisation Alkene carbons are sp2-hybridised Two p and one s orbitals are mixed to give three sp2 hybrid orbitals The sp2 orbitals have a trigonal planar arrangement, with the remaining p orbital

perpendicular to the plane

Bonding Head-to-head overlap of sp2 bybrid orbitals gives rise to a (sigma) -bondσ Sideways overlap of the p orbitals gives rise to a (pi) -bondπ The -bond is weaker than the -bond due to less efficient orbital overlapπ σ

Naming Alkene names end in ene

Isomers are possible with >3C

Isomers Stereoisomers are possible due to lack of rotation about C=C bond

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Stereoisomers diastereomers (non-mirror-image

stereoisomers) cis-trans isomers, geometric isomers

How would we classify/name these isomers?

Structural requirements for alkene diastereomers Each end of the C=C bond must have two different groups (i.e., A≠B, D≠E) (but A

& B can be the same as D & E)

Can’t classify these as cis-trans isomers as they are trisubstituted Require an alternative naming system

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Lecture 7

E/Z-nomenclature of alkenes Rules for assigning E/Z-stereochemistry of alkenes very similar to R/S-

stereochemistry of stereogenic carbon atoms

Rules for assigning E/Z Rule 1:

o Assign priorities to the groups at each end of the double bond (i.e. high/low at left end, high/low at right end) in same way as for R/S-designations (Cahn-Ingold-Prelog rules)

Rule 2:o If the high priority groups are one the same side (⇒ Z)-o If the high priority groups are one the opposite side (⇒ E)-

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Alkene isomerisation in biology

Aromatic compounds Historically, aromatic compounds were so named due to their distinctive odours

It was soon realised that these compounds differed in their chemical behaviour from other classes of organic compounds (such as alkanes, alkenes)

Aromatic compounds now refer to benzene and its structural relatives

Benzene Stability

Structure

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Benzene is a regular hexagon; all C-C bonds are the same length (139 pm; intermediate between a C-C single bond (154 pm) and a C=C double bond (134 pm)).

Benzene is planar, all bond angles 120°

Benzene: Reactivity

H2 / Pd(cat.) rapid reaction at, ambient temp., pressure

slow reaction at high temp., pressure

Br2 rapid bromination (addition reaction)

no reaction (substitution occurs) if catalyst added

Benzene does not behave like an alkene!

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Lecture 8

Benzene: Structure Proposed structures of benzene:

Kekule’s drawing of the resonance forms of benzene (1872);

Benzene: Resonance stabilisation

The two representations of benzene are resonance forms Neither is a strictly correct - the real structure of benzene is a hybrid of the

resonance forms The -electrons are not localised between specific carbon atoms -π they are

delocalised

The circle representation of benzene is sometimes used to represent the

delocalised electrons, but it is limited in that it doesn’t indicate how many -πelectrons are in the ring

Benzene: Resonance

Individual resonance forms are imaginary, not realo the real form is an average, or resonance hybrid, of the different forms

Resonance forms differ only in the placement of the - or non-π bonding electronso neither the position nor hybridisation of any atom changes

Resonance forms must obey the normal rules of valencyo be careful to assign correct charges and number of bonds

Different resonance forms don t have to be equivalent

The resonance hybrid is more stable than individual resonance forms

Orbital description

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6 sp2-hybridised carbons – each has a p-orbital with one electron

The two resonance forms conjure images of p-orbital overlap only to one side or the other...

But the resonance hybrid is better visualised as having the p-orbitals overlapping on both sides, resulting in delocalised electron clouds above and below the ring.

Requirements for aromaticity Cyclic

each atom ring is sp2-hybridised Conjugated(alternating double and single bonds)

Planar } necessary for overlap of p-orbitals

4n+2 -electrons (the Hückel rule) (n = integer)π

Heterocyclic aromatics

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Nomenclature

Some aromatic compounds have retained their historic trivial names

Others are names by a more systematic approach

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Disubstituted benzenes

1,2-disubstituted benzeneortho-substituted

(Greek; straight)

1,3-disubstituted benzenemeta-substituted

(Greek; after)

1,4-disubstituted benzenepara- substituted

(Greek; beyond)

2-nitrophenolortho-nitrophenol

(o-nitrophenol)

3-bromobenzoic acidmeta-bromobenzoic acid

(m-bromo...)

1-iodo-4-nitrobenzenep-iodonitrobenzene

(p-iodo...)

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Lecture 9

Alkynes Alkynes have the general formula CnH2n-2

Geometry Contain C≡C double bond Linear arrangement of atoms

C≡C bond length 1.20 Å C≡C bond strength 840 kJ.mol-1

Sp hybridisation

One p and one s orbital are mixed to give two sp hybrid orbitals

The sp orbitals have a linear arrangement, with the remaining two p orbitals perpendicular to these and each other

Bonding Head-to-head overlap of sphybrid orbitals gives rise to a (sigma) -bondσ Sideways overlap of two sets of p orbitals gives rise to two perpendicular -π

bonds

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Naming Alkyne names end in yne

Numbers used to define position of triple bond (as for alkenes)

Other sp-hybridised molecules Carbon dioxide

Allenes

Functional groups C-C and C-H bonds are strong and non-polar, and are therefore relatively unreactive The more reactive bond types/groupings are termed functional groups; e.g. carbon-carbon multiple bonds

o alkenes (C=C)o alkynes (C≡C)o aromatic compounds

functional groups incorporating heteroatoms (non-C,H)

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Lecture 10

1°, 2°, 3°, 4° centres Carbon can have up to four other carbons attached (referring to sp3-carbons only)

o 1 C-C bond ⇒ primary carbon (1°)o 2 C-C bonds ⇒ secondary carbon (2°)o 3 C-C bonds ⇒ tertiary carbon (3°)o 4 C-C bonds ⇒ quaternary carbon (4°)

1°, 2°, 3° functional groups A functional group attached to a 1° centre is referred to as a 1° functional group (and

so on) (most commonly for alcohols & alkyl halides)

tertiary (3°) alcohol

Secondary (2°) alcohol

secondary (2°) alkyl bromide tertiary (3°) alkyl chloride

primary (1°) alcohol primary (1°)

alcohol

Structure determination and spectroscopy How do we determine the structure of a compound isolated from natural sources or

synthesised in the laboratory? Various spectroscopic/spectrometric techniques provide information about

structure;o mass spectrometry: molecular weight/formulao UV spectroscopy: conjugated systemso IR spectroscopy: functional groupso NMR spectroscopy: C/H framework

Mass spectrometry The compound is vaporised and ionised by one of several techniques Traditionally, irradiation by an electron beam is used to generate a radical cation

(molecular ion, M+•)

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The molecular ion can break down into fragment or daughter ions The ions are separated according to their mass (m) and charge (z)

Mass spectrometer

Simple mass spectra

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Mass spectrum of hexane

Mass spectrum of 2,2-dimethylpropane The mass spectrum of 2,2-dimethylpropane has a very weak molecular ion at m/z =

72, but a strong peak at m/z = 57. The loss of a methyl group (15) gives rise to a very stable carbocation

The Electromagnetic Spectrum

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UV Spectroscopy

Conjugated systems absorb light in the UV region Electron excited from → * orbitalπ π The greater the conjugation, the lower the energy required, and therefore the

greater the wavelength Highly conjugated systems can absorb in the visible region (>400 nm), giving rise to

coloured compounds

UV Spectra

butadiene:

hexatriene:

octatetraene:

benzene:

max = 217 nmλ

max = 258 nmλ

max = 290 nmλ

max = 206, 254λ nm

-carotene: max = 455 nmβ λ

(absorbs in the blue region, resulting inan orange colour)

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Lecture 11

IR Spectroscopy

In infra-red (IR) spectroscopy, the frequency of the absorbed radiation is given in terms of the units reciprocal cm (cm-1) (also called wavenumbers )

IR range: 4000 → 400 cm-1 (2.5 → 25µm)

IR radiation corresponds to the energy of molecular vibrations (stretching, bending) Energy is absorbed if the frequency of radiation matches the frequency of the

vibration (resulting in increased amplitude of vibration) Different bond types have specific frequencies of vibration: IR spectrocopy gives us

information about the functional groups present in a molecule

Characteristic IR absorptions

Alkyl groups (C-H) 2800-3000 ignore! (in most organic compounds)

Alcohols (O-H) 3400-3600

Amines (N-H) 3300-3500 similar to O-H

Carbonyl compounds(C=O)

1670-1780 contained in many functional groups e.g. esters, amides, ketones etc.

fingerprint region <1500 used only to match identical compounds

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IR Spectra

Structure of an unknown

Mass spectrum indicates MW=60o Possible molecular formula: C3H8Oo Major fragment ion m/z = 45 (loss of 15; -CH3)

IR spectrum indicates OH group (strong, broad peak ~ 3350 cm-1)o no C=O at ~ 1700 cm-1

Most probably 2-propanolo stable fragment ion;

Need more data for definitive structure determination

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Structure determination and spectroscopy How do we determine the structure of a compound isolated from natural sources or

synthesised in the laboratory? Various spectroscopic/spectrometric techniques provide information about

structure;o mass spectrometry: molecular weight/formulao UV spectroscopy: conjugated systemso IR spectroscopy: functional groupso NMR spectroscopy: C/H framework

Nuclear magnetic resonance (NMR) Many types of nuclei have a spin, and because they are charged, they therefore act as

tiny bar magnets! In the presence of an external field, the nuclei can either be aligned with or against

the applied field

These spin states are of slightly different energies. If they are irradiated with the appropriate frequency, the nuclei of the low-energy state absorb the energy and spin-flip to the high energy state.

Typically, superconducting magnets of 5-12 tesla (T) are used, requiring radiowaves (200-500 MHz) for resonance

1H and 13C nuclei are most commonly used, as they allow for a map of the carbon-hydrogen framework of a molecule to be determined

Only 1% of carbon nuclei are 13C, so carbon NMR spectroscopy is less sensitive that hydrogen NMR (proton NMR) spectroscopy

NMR Spectroscopy The radiofrequency required to bring a nucleus into resonance is proportional to the

strength of the magnetic field. However, every nucleus is surrounded by electrons which set up tiny local magnetic

fields Each type of nucleus resonates at a slightly different frequency (the differences are

in parts per million, ppm!), depending on the effective field at each nucleus.

Beffective = Bapplied – Blocal

NMR spectrum provides information of the number and type of H or C environments

1H and 13C NMR spectra of methyl acetate

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6 hydrogens in total, but only

two different environments: all Hs in a CH3 group are equivalent

Tetramethylsilane (TMS, (CH3)4Si) is used as a reference and is arbitarily set to 0 ppm 3 carbon atoms all are different, giving 3 peaks

13C NMR spectroscopy The most common form of 13C NMR spectroscopy, proton-decoupled 13C NMR,

removes interference from neighbouring hydrogens and gives a separate signal for each different carbon environment

The number of carbon environments is determined by elements of symmetry present in the molecule

The position of each signal is determined by the electronegativity of nearby atoms, and other factors

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39

Lecture 12

13C NMR spectroscopy

Shows number of non-equivalent hydrogens Size of each peak (integration of area under each peak) is proportional to the

number of hydrogens in each environment

Peak Integration

bromoethane2 signalsratio 2 : 3

2-bromopropane2 signalsratio 1 : 6

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Spin-spin coupling

The position a signal occurs in the spectrum (the chemical shift) is determined by the effective magnetic field at that hydrogen nucleus.

But each hydrogen is itself acting as a tiny magnet; each H is therefore affected by the other H atoms around it.

The signal is split into multiple lines as the nearby hydrogens can be aligned with or against the applied magnetic field, slightly varying the effective field

n+1 ruleo Number of lines observed for a hydrogen with n hydrogens on adjacent

atoms is n + 1o The ratio of the intensities of the lines making up the multiplet is given by

Pascal s triangle:

o Distance between peaks in a multiplet is the coupling constant (denoted J, measured in Hz)

1H NMR spectroscopy is a very powerful technique: Number of different H-environments

o Number of peaks

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Type of H-environment (nearby functional groups)o position of peak (chemical shift, )δ

Number of equivalent H s in each environmento integration of peak area

Number of adjacent H so spin-spin coupling, n+1 rule

IR spectrum: C=O, no OH

UV spectrum: highly conjugated system

Mass spectrum: MW = 136C8H8O2 fragments 107 (–29, loss of Et• or •CHO)

92 (further –15, Me•)

13C NMR: 6 peaks (some symmetry)

1H NMR: CH singlet (no adj H)2 doublets (CH-CH)CH3 singlet (no adj H)

IR spectrum: C=O, no OH

UV spectrum: highly conjugated system

Mass spectrum: MW = 136 C8H8O2fragments 107 (–29, loss of Et• or •CHO)

92 (further –15, Me•)

Magnetic resonance imaging (MRI) 1H NMR of the body Detects water content/environment Complementary to X-ray (visualises soft tissue rather than hard tissue) Used to detect tumours, Alzheimer’s, sports injuries, etc. Pioneers (Profs Paul Lauterbur & Peter Mansfield) awarded 2003 Nobel Prize in

medicine

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Organic Chemistry Notes

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