key concepts for MCQ test Flashcards
can sigma bonds rotate freely?
yes
can pi bonds rotate freely?
no
what type of spins do electrons have in covalent bonding?
opposite
bond dissociation energy
measure of how strong a bond is.
when you bring 2 atoms together there is a release of energy, so to break the bond you need to put energy back in
electronegativity
ability of an atom to attract a shared paired of electrons/ electron density towards itself. It is a chemical property
what is electronegativity determined by?
- nuclear charge (more protons = more pull of electrons to nucleus)
- location of electrons in orbitals
- electron shielding
inductive effect
- effects of electronegativity on charge distribution of a molecule
- dipoles arise due to differences of electronegativity in atoms
groups that are more electronegative than a carbon atom (delta negative)?
- halogens
- NO2
- OH
- SH
- SR
- NH2
- NHR
- NR2
- CN
- carboxylic acids
- aldehydes
- ketones
groups that are LESS electronegative than carbons (delta positive)?
- alkyl R groups
- metals (Mg)
why does the pka decrease when more chlorines are added to a carbon next to a carboxylic acid?
- cl is electronegative
- so electron density is being pulled towards the chlorine
- this causes the negative charge to stabilise across the anion
- decreasing the pKa
- so molecule with 3Cl is more stable due to e- being pulled towards all 3
what are resonance forms?
electrons are delocalised into the model (resonance = e- arranged differently)
mesomeric effect
lone pair next to a pi bond
(overlap of lp of e- in a p orbital with adjacent pi bonding systems)
electron withdrawing substituents and the mesomeric effect
-M
- electrons are withdrawn from the pi bond.
- orbital overlap causes the p orbital be low in electron density,
- decrease in pKa, stronger acid, more stable.
electron donating substituents and the mesomeric effect
+M
- lp donate electrons to the pi system.
causes pKa to increase so weaker acid.
so it is less stable
what does it mean if the pH of a sol is equal to the pKa?
solution is 50% protonted
what does the alkyl group in an alkyl amine do?
- alkyl group is electron donating (+M)
- so pushes electrons towards the N atom
- N becomes more negative
- so more attractive to H+
why can the lone pair on a N atom of phenylamine not pick up a proton?
- lone pair is sp2 hybridised
- overlaps with aromatic ring
- reduced availability to accept proton as the lone pair is delocalised into ring system
- phenyl amine = weaker base
why can the lone pair on N atom of pyridine pick up a proton?
- lone pair is pointing away from the pi system
- lp is in an sp2 orbital
- can accept proton
- as lp is available and not delocalised into ring system
- pka still low so weak base
pKa of amides
- amides have a very low pka
- lone pair on N is sp2 hybridised
- lp in p orbital overlaps with the carbonyl =O bond (pi bond)
- so lp not available to accept proton
in order to protonate an amide what must you have?
VERYY low pH
how do carbonyls react?
- polar oxygen is electronegative
- pulls e- density towards it
what determines how electronegative the =O of a carbonyl is?
the functional groups attached to it
what do strong electron donating groups (e.g OH) do to carbonyls?
makes the delta + on carbon smaller (reduces difference in electronegativity of c and o), so makes reactivity towards Nu weaker
what do strong electron withdrawing groups (acyl chlorides) do to carbonyls?
makes delta + on carbon bigger (bigger difference of electronegativity of atoms) so reactivity towards Nu increases
name all functional groups you didn’t know before
- ether
- thiol (SH)
- lactone (ester in a ring)
- disulphide bridge (R-S-S-R)
- lactam (amide in a ring)
- beta lactam
what is the alpha position?
position next to carbonyl
describe amides
- mesmeric effect due to lone pair on N next to the pi bond (carbonyl)
- lp not available
- NOT basic
hybridisation of an ether?
sp3
hybridisation of a ketone?
sp2
hybridisation of an ethyl ester?
sp2
hybridisation of an a primary amine?
sp3
hybridisation of a primary amide?
sp2
hybridisation of a thiol?
sp3
pka of HCl?
-7
pka of CH4?
about 50
pka of carboxylic acid?
about 5
pka of phenol?
~ 10
pka of alcohol?
~ 15
keto vs enol
keto: the one with the ketone
enol: the one with the alkene and alcohol
bc the H jumped over
carbocycle
rings made of C atoms
saturated
no double bonds
heterocycles
contains heteroatoms (O,S,P,N)
e.g cyclic ethers
epoxide/ oxIrane (heterocycle) - example of cyclic ether
2 membered carbon ring with one oxygen in it
oxEtane - cyclic ether
3 membered carbon ring with one oxygen in it
cyclic amines (HINT: IDINE)
- azIridine: 2 membered carbon ring with NH in it
- azEtidine: 3
- pyrrolidine: 4
- piperidine: 5
unsaturated version of pyrrolidine (4 C) - 2 double bonds
pyrrole
unsaturated version of piperidine (5 C) - 3 double bonds
pyridine
2 factors in ring formation + activity
- entropy: bigger ring size = ends less likely to meet = ring less likely to form = smaller rigs favoured
- ring strain
what is ring strain?
- smaller rings have smaller bond angles that deviate from the primal bond angle that comes from hybridisation
- smaller rings disfavoured
rate of formation of ring sizes?
5 > 6 > 3»_space; 4
- 5 membered easier to form than 6
- 6 is faster than 3
- 3 is a lot faster than 4
reactivity of 5 + 6 membered rings?
- stable
- due to little ring strain
reactivity of 3 + 4 membered rings?
- susceptible to ring opening
conformational isomer definition
compounds with different arrangement of atoms from BOND ROTATION (so occurs in sigma bonds)
staggered conformation isomer
- lower in energy
- C-H bonds are further away
eclipsed conformation isomer
- higher in energy
- C-H bonds closer
axial vs equatorial
axial = higher in energy
equatorial = lower in energy
configurational isomer definiton
compounds with different arrangement of atoms from BOND BREAKING (occurs in double bonds)
geometric isomers
E/Z, cis trans
optical isomers
non superimposable mirror images of each other (enantiomers), identical physical properties, rotate PPL in opposite but equal directions
chiral molecule
no plane of symmetry within
achiral molecule
plane of symmetry within
PPL
- light source
- light goes in all directions
- so you put filter
- light goes in one orientation
- see observed rotation
anticlockwise vs clockwise PPL
anticlockwise = l or -
clockwise = d or +
how to find alpha D?
observed rotation / pathlegth (dm) x conc (g/mol)
REMEMBER THE PLUS OR NEG SIGN
USE THIS TO FIND MIXTURE OF SAMPLE WITH NUMBER LINE
cm to dm
divide by 10
racemic mixture and its alpha D
50:50 mixture of 2 enantiomers
- alpha D is 0 as PPL is cancelled out
achiral compound alpha D
0 as PPL only occurs in chiral compounds
enantiomeric excess (also the number line stuff)
excess of one enantiomer over another.
ee= x-y/ x+y (use the percentages of + or - enantiomer for this)
what 2 things go on the number line?
- the % of + or - enantiomer (depends on what answer you got for alpha d)
- alpha d of the pure sample
do lone pairs count in assigning s and r?
NO
clockwise vs anticlockwise for S and R assigning
s = anti
r = clockwise
NOTE: if lowest group isn’t wedged THEN THE ORIGINAL ANSWER NEEDS TO BE SWITCHED
what does keto-enol tautomerisation do?
destroys stereogenic centre
enantiomers that can racemise?
thalidomide and ibuprofen via tautomerisation
enantiomers that can’t racemise?
citalopram and escitalopram
enantiomers vs diastereoisomers
enantiomers = RS and SR, RR and SS
distereoisomers = RS and RR, RS and SS
epimers
when disteroisomers differ at only one sterogenic centre (RRRS)
good leaving group meaning?
can stabilise a negative charge (e.g Cl)
SN2 reaction (nucleophilic substitution)
- substitution nucleophilic bimolecular
- Nu- goes via 180 degree attack
- via transition state
- inversion of stereochemistry
- 2 things come together
factors for SN2 reaction?
- good, small Nu-
- primary and secondary substrates (1/2 alkyl groups only) otherwise hard for Nu to attack
SN2 reaction energy profile
- reactants higher than products
- one big increase (Ea) for the transition state
- exothermic reaction (energy lost to surrondings when bonds are broken)
SN1 reaction (nucleophilic substitution)
- the leaving group just leaves in the first step no need for Nu -
- Nu - attacks in the carbocation intermediate stage due to empty p orbital (which is trigonal planar sp2)
- forms product
factors favouring SN1
- good leaving group
- weak and large Nu
- stabilised carbocation
SN1 energy profile
- reactants higher than products
- LG leaving is highest peak as most difficult step (RDS)
- Nu attacking ring is slightly lower energy than this
- exothermic
E2 reaction (nucleophilic substitution)
- elimination bimolecular
- base removes proton of an alkane
- so the electron in bond moves across
- forms an alkene
- so LG has to leave
(base attacks proton in plane of LG)
E1 reaction (nuc sub)
- elimination unimolecular
- LG just leaves
- so carbon becomes positively charged (carbocation intermediate)
- base with negative charge removes proton
- electrons in bond move across
- form alkene
most reactive to least reactive carbonyls
- acyl chloride
- acid anhydride
- aldehyde
- ketone
- ester
- amide
how to make acid anhydride?
CA + CA
where do inductive effects occur?
through sigma bonds (so oxygen in carbonyl pulls e- out of c via sigma bond)
what are protons at the alpha position?
acidic
why are acyl chlorides more reactive than acid anhydrides?
- due to LG ability
- Cl- is better leaving group + more reactive, produces more stable acid HCl
- pka is -7 (stronger acid)
- carboxylate ion not as good LG, pka = around 5 of ethanoic acid
so smaller pka = better LG
why are aldehydes more reactive than ketones?
- inductive effects
- ketone has 2 inductive effects, which make the electronegativity difference smaller between c and o, so less electrophilic + reactive
- aldehyde has 1 inductive effect, so carbon is more delta positive
why are esters more reactive than amides?
oxygen is more electronegative than N so it pulls more electron density from the carbonyl carbon, so esters more reactive
why are esters and amides not very reactive?
- due to mesomeric effects
- lp of electrons next to pi bond
- pushes electrons back to carbonyl carbon, so more electronegative, less electrophilic
rotamers
- mesomeric effect causes double bond characteristics in C-N bond
- restricted rotation
- causes rotamers
carbonyl + H2O (without a leaving group)
- tetrahedral intermediate forms
- proton transfer
- you form a hydrate (2 alcohol functional groups attached)
is eqm heavily acetone or its hydrate side?
acetone (major product)
is eqm heavily on formaldehyde or its hydrates side?
hydrate (major)
as the aldehyde is a strong electrophile so accepts e-
is eqm heavily cyclic ketone or its hydrate side?
hydrate (major) as it is sp3 so 109 degrees. due to steric it wants to be 120 degrees, 109 closer than 60
carbonyls + alcohol R-OH (without LG)
- use acid catalyst to protonate the =O bond (makes it + charged)
- forms tetrahedral
- remove the H+ to form hemi ketal/ acetal
- H+ added again but onto the OH to form OH2
- C=O reforms and H20 is leaving group
- O becomes + charged again as R group attached to it
- R-OH attacks again
- forms tetrahedral again but with new R-OH on it
- called ketal or acetal
carbonyl + primary amine (without LG)
forms iminium which forms immune after being deprotonated
biosynthesis of a.a
pyridoxamine + pyruvic acid undergo condensation to form imine, double bond moves, water added, forms alanine
carbonyl + secondary amine (with LG)
forms iminum which forms enamine
how to make an ester with acyl chloride?
- acyl chloride + alcohol
- tetrahedral intermediate
- o- forms double bond
- so cl- leaves
- ester made
- very reactive no need for cat ha
how to make an ester with carboxylic acid?
- CA + alcohol
- acid catalyst to protonate to make it more electrophilic
- proton transfer
- O reforms
- H2O leaves
- proton on =O leaves
- ester formed
how to make an amide with acyl chloride?
acyl chloride + primary amine
CA + amine makes?
acid + base makes salt
carboxylate ion and NH3 species
how does nature make amide bonds from CA?
- thioesters
- acetyl CoA
- acyl phosphate
how is glutamate made?
- the CA is phosphorylated (ATP to ADP)
- this reacts with ammonia
acid hydrolysis of ester
- =O protonated to make more electrophillic
- proton transfer with this product
- lose H+ to remake =O
- make CA and OH
basic hydrolysis with ester
- base attacks carbonyl carbon
- OR becomes LG and leaves when =O reforms
- forms CA + OR-
- but irreversible reaction happens where it becomes carboxylate ion
acid hydrolysis of amine
- electrophile made more electrophullic by protonation
- makes O positively charged
- water attacks
- proton transfer
- NH3 becomes LG when O reforms
- H from protonation is lost
you make CA and NH3 / NH4+
basic hydrolysis of amine
- OH attacks (slow)
- NH2 leaves when O reforms
- very slow due to bad LG
- also forms irrevisble carboxylate ion
resonance vs tautomer
resonance = electrons arranged differently
tautomer = atoms arranged differently
keto / enol
constitutional isomers, diff compounds, diff structure, same molecular formula
acidity of alpha proton is related to?
order of reactivity of carbonyl
why is acyl chloride > ketone > ester > amide ?
acyl chloride has bigger inductive effect due to bigger delta plus so alpha proton is more acidic (pka ~ 15)
pka of ketone
~ 20
pka of ester
~25
pka of amide
~ 30
why is do we draw oxyanion and not carbanion enolate?
oxygen more EN than carbon so O- more stabilised, so C more reactive.
describe double bond
region of high electron density, nucleophilic, isolated (not conjugated)
when alkene under electro add is 2-chloropropane or 1-chloropropane not observed?
1-chloro
-regioselectivity
- regioisomerism
why is 1-chloropropane not observed?
- primary carbocation intermediate
- not very stable
why is secondary carbocation preferred?
- inductive effects: alkyl groups are weakly electron donating so push e- to carbon, causing smaller delta negative. secondary has 2, primary has 1
- hyperconjugation: orbitals overlap, which has stabilising effect
allylic carbocation
- double bond moves across to stabilise + change
- so + charge is delocalised over both carbons
- increases stability
issues with original benzene model
- c-c bond lengths in benzene are not usually size of c-c single bonds
- all bond lengths are same
(resonance explains this)
describe the correct benzene model
delocalised pi bond system above and below plane, sp2 120 degrees
define aromaticity
electrons are delocalised over whole CONJUGATED systems
define conjugation
alternating double, single, double bond
rules to assign something as aromatic
- cyclic
- flat (trigonal planar sp2)
- conjugated
- 6 pi electrons (remember if lp is part of ring system it counts)
what do aromatics undergo?
electrophilic substitution
aromatic + halogen (Cl2)
- requires lewis acid
- AlCl3
- e.g chlorobenzene
- halogenation
aromatic + acyl chloride
- Lewis acid
- alcl3
- forms the ketone on the ring
- acylation
aromatic + haloalkane
- Lewis acid
- alcl3
- alkylation
aromatic + H2SO4
- forms SO3H
- sulfonylation
aromatic + conc HNO3 + conc H2SO4
makes nitrobenzene
ortho, meta, para directing groups
ortho = 1,2
meta = 1,3
para = 1,4
if an R group on a benzene ring is strongly electron donating what does this mean? e.g NH2, NHR, NR2, OH, OR
- electrons are pushed into the Nu making it more nucleophilic
- 1,2 and 1,4 activating
- ortho and para directed
if an R group on benzene ring is weakly electron donating what happens? e.g methyl, ethyl, phenyl
- 1,2 and 1,4
- ortho and para
if an R group is strongly electron withdrawing what happens? e.g ketone, ester amide, nitrobenzene, nitrile
- electron density pulled out of Nu, so less nucleophilic
- directs meta 1,3
if an R group is weakly electron withdrawing what happens? e.g halogens
ortho 1,2 and para 1,4
SnAr
- nucleophullic aromatic substitution to identify a.a structure
- ## –R in ring but you don’t know where substituents are
what is used to identify a.a sequences
sangers reagent (specifically a.a at n terminus)
what is an alpha, beta unsaturated ketone?
- enone
- electrophillic so toxic
- alpha position next to ketone pi bond has double bond
- could also have a,b unsaturated ester, amide, aldehyde
- conjugated
- has 2 electrophilic positions so Nu can attack at either
- can form allylic cation
direct addition (1,2 addition)
- nu attacks where the c=o bond is
- if LG present you get the product with c=o in it
- if LG not present you get the alcohol
conjugate addition (1,4 addition . Micheal addition)
- nu attacks at 4 position where c=c is
- acid used to turn alkene into alkane
enone reactivity
- acyl chloride reacts readily 1,2
- amide reacts readily 1,4 as the actual amide isn’t that reactive, so the c=c is chosen over it
glutathione
delivery system of thiol used to detoxify things in body, e.g paracetamol
