Topic 3 - Organic Chemistry

Question 1

What is a heteroatom?

Answer 1

An atom other than carbon or hydrogen that is found in an organic molecule.

Question 2

Definition of the functional group?

Answer 2

The part of the molecule that is functional. Usually, the part containing the heteroatom. Chemical reactivity of molecules is associated with functional groups.

Question 3

Definition of resonance?

Answer 3

When more than one arrangement of double bonds needs to be drawn in order to show electronic distribution; we say that the molecule exists as a resonance hybrid.

Question 4

Requirements of an aromatic molecule?

Answer 4

To be aromatic a compound must be planar and cyclic and have (4n+2) delocalised pi electrons, where n is an integer.

4n+2 –> known as Huckles law –> number of delocalised electrons must fit.

Hence, according to Huckles law, you can have 2 (n=0), 6 (n=1), 10 (n=2), etc…. Pi electrons.

Question 5

Definition of tautomer?

Answer 5

Tautomer is an example of a specific kind of isomer.

Structured isomers that differ only in the position of a hydrogen and a double bond.

Tautomerisation is the transformation of one tautomer to the other.

Keto-enol tautomerisation and imine-enamine tautomerisation are very important for biological systems.

Question 6

Example of resonance?

Answer 6

Resonance example –> Carboxylate (COO^-)

Question 7

What are the two main types of tautomers?

Answer 7

1. Keto-enol tautomerisation

Keto <—–> Enol

(aldehyde) (Double/alcohol)

Basically, hydrogen and double bond swap position.

2. imine - enamine tautomerisation

imine <—–> enamine

Note tautomerisation becomes more favourable under specific acid/base conditions.

Question 8

Definition of nucleophile?

Answer 8

A nucleophile is an electronegative functional group which has an electron pair that can be used to form a covalent bond.

• Attracted to positive charged

Example –> H₂O

Question 9

Definition of Electrophile?

Answer 9

An electrophile is an electron deficient group which can accept a pair of electrons to form a covalent bond; must possess an empty orbital.

• Attracted to the negative charge

Example –> carbon of carbonyl

Question 10

Definition of polarized bond?

Answer 10

This is when the electrons are not shared evenly between two joined atoms.

The bond has a dipole moment.

Question 11

Definition of polarizability?

Answer 11

Its a measure of the ease of change of electron distribution –> Basically how easy it is to cause a dipole moment.

Example:

Small atom –> less shielding –> harder to cause dipole moment as electrons are held close to the nucleus.

Big atom –> more shielding –> easier to cause dipole moment as electrons are further away from the nucleus.

Question 12

Definition of electronegativity?

Answer 12

A measure of how strong the atom attracts electrons in a bond.

Question 13

Definition of a leaving group?

Answer 13

The part of the molecule which takes bonding electrons when a bond is broken during a biochemical reaction.

Question 14

What is hybridisation? What are the three main types?

Answer 14

Hybridisation refers to the mixing of atomic orbitals to make molecular orbitals. The shape/orientation of these new hybrid orbitals are optimised for bond formation.

1. Sp³
2. Sp²
3. Sp

Question 15

What are the rules for determining hybridisation?

Answer 15

1. Carbon atoms and heteroatoms are always Sp³ hybridized if all the bonding is single.
2. Carbon to carbon double bonds are always Sp²
3. Partial double bonds are always Sp² –> Pi orbitals are used to form delocalised system
4. Triple bonds are Sp hybridised –> very rare in biological systems.

Question 16

Explain the shape and main facts of Sp³ hybridisation.

Answer 16

1. 1 S and 3 P orbitals combine to form 4 hybrid orbitals of identical shape/energy –> tetrahedral arrangement.
2. Hybrid orbitals can undergo head-on overlap with other orbitals to form sigma bonds.
3. If there are fewer than 4 bonds –> there must be a lone pair.
4. Lone pair distorts tetrahedron –> can act as base or nucleophile –> also involved in H-bonding.

Question 17

Explain the shape and main facts of Sp² hybridisation.

Answer 17

1. Combining of 1 S and 2 P orbitals to form Sp² hybrid orbital –> this leaves one P orbital.
2. All three hybrid orbitals are identical energy and shape —> trigonal planar arrangement.
3. All hybrid orbitals lie in the same plane whereas P orbital is perpendicular to the plane.

Question 18

What are the important oxygen based function groups?

Answer 18

Oxygen-based function groups include:

1. Hydroxyl
2. Alkoxyl (ether)
3. Carbonyl (Aldehyde/ketone/carboxylic acid/esters)

Question 19

What are the important nitrogen based functional groups?

Answer 19

Nitrogen-based functional groups

1. Amino - NH₂
2. Amide - C(O)NH₂
3. Imine - C=N-R

Question 20

What are some important sulfur based functional groups?

Answer 20

Sulfur-based functional

1. Thiol –> R -SH
2. Thioether –> C-S-C
3. Thioester –> R-C(=O)-S-R

Question 21

Describe hybridisation and important properties of -OH?

Answer 21

Hydroxyl

• Has two lone pairs which can act as nucleophilic/basic?
• Only single bonds –> Sp³
• Involved in a lot of H-bonding
• OH released –> forms water.

Question 22

Describe hybridisation and important properties of ether?

Answer 22

Ether

• Sp³
• Not a good leaving group
• Not involved in a lot of metabolism instead it is normally part of backbone structures.
• It is not a good nucleophile as the carbon would gain a positive charged and nothing can be removed to get rid of this positive charge.

Question 23

Describe hybridisation and important properties of carbonyl (ketone + aldehyde)?

Answer 23

Carbonyl (ketone + aldehyde)

• Sp² –> everything in the same plane except P orbital
• The difference in electronegativity creates a dipole.
• This makes carbon an important electrophile -> as it is positively charged.
• Important note –> Carbonyl molecules almost always have a hydrogen on the alpha carbon (carbon next to functional group). Hydrogen on alpha carbon is easily lost –> acidic –> this is also favourable as the structure becomes stabilised by resonance.

Question 24

Describe hybridisation and important properties ester?

Answer 24

Ester

• Sp² –> due to resonance formed
• Usually thioester is preferred in biological systems –> more reactive
• In resonance form the oxygen (not carbonyl oxygen) doesn’t pull electrons away from carbon –> instead it pushes electrons towards it to make it less reactive –> makes the ester less reactive than carbonyl.

Question 25

Describe hybridisation and important properties of amine?

Answer 25

Amine - Sp³ - At physiological pH --\> gets protonated --\> hence it is considered an acid. Conversely for -COO^-.

Question 26

Describe hybridisation and important properties of amide?

Answer 26

Amide - Can form resonance --\> Sp² - In resonance form, the lone pair is not available --\> not basic or nucleophilic. - Resonance thus decreases reactivity/electrophilicity of carbon.

Question 27

Describe hybridisation and important properties of imine?

Answer 27

Imine - At basic physiological pH becomes protonated - Protonation --\> nitrogen pulls strongly on electron --\> carbon becomes highly electrophilic. - More electrophilic than carbonyl - Known as a Schiff's base.

Question 28

If electrons are used in a ring system can they be used for other reactions?

Answer 28

No!

Question 29

Difference between Sulfur containing functional groups and O/N containing functional groups?

Answer 29

- Sulfur --\> larger orbital --\> electrons are further away from the nucleus --\> makes the electrons more polarizable. - Sulfur can't interact with hydrogen --\> due to size difference --\> no hydrogen bonding. - Normally hybridisation changes when N and O are connected to a carbonyl but not S. Ester + amides ---\> resonance Thioester --\> No resonance

Question 30

Describe hybridisation and important properties of thiols?

Answer 30

Thiols - R-SH - Sp³ - Very reactive - Polarizable - Similar chemistry to -OH but No hydrogen bonding - Not basic - Can be oxidised to form S-S bridge

Question 31

Describe hybridisation and important properties of Thioester?

Answer 31

Thioester - Sp³ hybridisation of sulfur - No resonance stabilisation - Carbon --\> strong electrophile/very reactive --\> Oxygen and sulfur both pull away electrons.

Question 32

Describe hybridisation and important properties of thioether?

Answer 32

Thioether --\> R -- S -- R - Sp³ - The sulfur equivalent of ether --\> but more reactive - Can be oxidised to sulphoxide and sulphone.

Question 33

Important reminders when using arrows in mechanisms.

Answer 33

1. The arrow shows where the electron pair is moving from and where it is going to. 2. The tail of arrow starts at lone pair or bond 3. The head shows where the electron ends up --\> either in a bond or as a lone pair. Arrows can not diverge from and converge to a single point.

Question 34

The three main type of organic mechanisms in biosciences?

Answer 34

1. Substitution (Normal Sp³ substitution (SN1/SN2) or Sp² Substitution (carbonyl) or Claisen condensation). 2. Addition -\> to C to C D.B or Carbonyl D.B or aldol (between two carbonyl compounds) 3. Elimination Note - addition and elimination are like the reverse of each other.

Question 35

What is the difference between SN1 and SN2 mechanisms? (Nucleophilic substitution)

Answer 35

SN1 --\> only 1 molecule is involved in the determining step (2-step mechanism) SN2 --\> 2 molecules involved in the rate-determining step (1 step mechanism).

Question 36

Draw and explain the mechanism for the SN1 mechanism?

Answer 36

1. Leaving group leaves --\> takes electrons --\> forms carbocation intermediate 2. The carbocation is Sp² --\> P orbital is empty --\> Nucleophile attacks from above and below the plane. 3. Nucleophile bonds --\> gives electrons --\> forms positive charge --\> Forms product which is Sp³ --\> racemic mixture but in biological systems only one --\> enzymes control.

Question 37

Draw and explain the mechanism for the SN2 mechanism.

Answer 37

1. Nucleophile attack from the opposite side of leaving the group --\> same time C -- X starts breaking (X = leaving the group). 2. Transition state formed --\> partial bond --\> Sp² during transition. 3. Leaving group leaves --\> product is Sp³ but with reverse stereochemistry.

Question 38

What are elimination reactions? What are the two types?

Answer 38

In elimination reaction, the leaving group simply leaves and is not replaced --\> usually results in the formation of a double bond. Two types: 1. E1 2. E2

Question 39

Draw and explain the mechanism for the E1 mechanism.

Answer 39

1. Exactly the same step as the first step in SN1 --\> leaving group leaves and takes electrons --\> hybridization to Sp² 2. Base steals H from alpha carbon and the electron from the hydrogen is used to form a double bond (enters P orbital).

Question 40

Draw and explain the mechanism for the E2 mechanism.

Answer 40

Very similar to E1 but everything happens at the same time.

Question 41

Explain and draw what happens in an addition reaction.

Answer 41

Reverse of elimination 1. electrons in double bond attack electrophile 2. Creates carbocation intermediate 3. Nucleophile binds to positive carbocation.

Question 42

Draw and explain the nucleophilic addition reaction of water to a double bond.

Answer 42

1. Electron cloud is nucleophilic and it is disrupted when bond with H⁺ is formed. Normally H⁺ binds to any carbon but enzymes control the bonding in bio systems. 2. Water (nucleophile) bonds to carbocation with lone pair. 3. Oxygen in water becomes positively charged as it uses one electron to form a double bond. Hydrogen gives an electron to oxygen (neutral again) when base bonds to Hydrogen. 4. This forms an alcohol.

Question 43

Draw the nucleophilic addition to a carbonyl double bond.

Answer 43

Note carbonyl can be replaced by imine. 1. Nucleophile attacks electrophilic carbon. 2. To allow nucleophile to bond --\> oxygen from carbonyl take electron from double bond --\> becomes negatively charged --\> rehybridisation to Sp³ 3. Intermediate form -- Negative oxygen gets protonated while positive Oxygen (nucleophile added) gets deprotonated by a base. 4. The product formed --\> Hemiacetal ---\> One hydroxyl and one ether. The process is used to make sugar cyclic.

Question 44

How is cyclical glucose created from the linear form?

Answer 44

Linear glucose undergoes addition reaction between -OH (carbon 5) and Aldehyde (carbon 1) to form a cyclical molecule.

Question 45

Explain and draw the aldol reaction?

Answer 45

A specific type of nucleophilic addition --\> Natures favourite way of building bigger molecules. Involves two carbonyl compounds --\> One acts as nucleophile other as an electrophile. 1. The first step is the removal of hydrogen from alpha carbon with the help of a base (not shown) 2. Negative carbon acts as a nucleophile and attacks electrophilic carbon on another carbonyl molecule. 3. Forces oxygen on electrophilic carbon to take the electron --\> negatively charged. 4. O^- accepts the electron --\> product β hydroxyaldehyde. Note --\> Aldol reaction is reversible (exactly the reverse) --\> aided by the presence of enzymes.

Question 46

Draw and explain the nucleophilic substitution of a thioester. Different to normal Sp³ nucleophilic substitution.

Answer 46

Sp² - substitution. 1. Nucleophile attacks electrophilic carbon --\> Oxygen on carbonyl becomes negatively charged --\> Note mistake in the diagram --\> double bond is no longer present in the intermediate 2. Oxygen reforms double bond --\> push of leaving the group. 3. Positively charged nucleophile (H₂O) forms carboxylate ion as the H⁺ is lost. Basically in this reaction... Thioester is broken down to carboxylate and thiol.

Question 47

Explain and draw the Claissen condensation reaction. A specific type of substitution reaction.

Answer 47

Consists of one Nucleophile and One electrophile. 1. Base removes a proton from alpha carbon --\> Hydrogen leaves electron to form C=C which results in C--O^- formation. 2. Carbon double bond acts as a nucleophile and attacks the electrophilic carbon on the other molecule. 3. Electron fro C--O^- moves back to form double bond --\> pushes off leaving group Product --\> β keto thioether.

Question 48

Difference between homolytic and heterolytic cleavage?

Answer 48

Heterolytic cleavage occurs when the valence electrons are distributed differently (unequally) between two atoms. Homolytic cleavage occurs when the valence electrons are distributed in the same way (equally) between two atoms.

Question 49

What are the two key groups of nucleophiles?

Answer 49

1. Molecules or ions with non-bonding pairs of electrons. 2. Molecules with a multiple (double or triple) covalent bond --\> rich source of electrons --\> Pi bond provides electrons because electrons are at a higher energy level --\> less strongly attracted to nuclei --\> more polarizable.