PHAY0002; Acids & Bases (reactions)

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Abi s

Cards (45)

What is a Bronstead Lowry acid and base
BLA=a substance that can donate a proton (H+)
BLB= a substance that can accept a proton
what is the name of the base/acid after accepting/donating a proton?
conjugate acid= name of base after it has accepted a proton
conjugate base= name of acid after it has donated a proton
what characterises a strong base/acid? What is the strength of an acid by?
-the strongest acid is the one that gives up its proton most readily
-the strongest base is the one that accepts a proton most readily
-the strength of an acid is measured by its dissociation constant (Ka); this is a reflection of how readily the molecule will donate its proton
why is Ka higher for stronger acids?
-the strong acid gives up its proton more meaning the forward reaction occurs more
-this means the concentration of H3o+ and A- is higher
-using the equation, this means Ka will be higher
what is the equation linking pKa and kA
pKa = -(logKa)
why is Ka important in pharmacy
-influences the degree of acidic and basic drugs which will give info as to the extent and site of absorption from the gut after oral administration
-allows us to predict what proportion of a drug is ionised at a given pH and thereby predict the charge on a molecule anywhere in the body; important when thinking about how drugs bind to their targets
-helps to inform us at what pH a drug is likely to be soluble in water & whether drugs can be mixed together in the same solution
how does pKa & Ka link to acidity & basicity? 
high Ka, low pKa = highly acidic
low Ka, high pKa= weakly acidic (more basic)
what is a Lewis base/acid?
Lewis acid= a substance capable of accepting an electron pair
Lewis base= donates an electron pair
*a proton is a lewis acid because it readily accepts an electron pair e.g. from water to fill its valence shell
What kind of atoms can act as a lewis acid?
Any atom with an incomplete valence shell - they readily accepts a pair of electrons from atoms that have lone pairs available to donate
-these kind of Lewis acids are often used as catalysts in reactions of aromatic compounds
what determines whether water acts as an acid or base?
-a sufficiently strong acid e.g.HCl can force water to accept a proton causing it to behave as a base
-a sufficiently strong base can force water to donate a proton and behave as an acid
*how strong the bases & acids are in relation to one another will determine where an equilibrium lies
what does amphoteric mean 
-substances that can act either as acids or bases are said to be amphoteric
how do we determine where the equilibrium of a reaction lies? e.g. acid-base reaction between water and HCl
-compare strengths of acid and conjugate acid (compare pKa)
-lower pKa = stronger acid
-HCl is a better acid so dissociates more
-pushes equilibria to RHS
How do we determine where the equilibria of a reaction lies? e.g. Ammonia and water
-compare the pKa of the acid and the conjugate acid
-pKa of the conjugate acid is higher
-conjugate acid is a stronger acid and so is more likely to dissociate (backward reaction)
-equilibrium lies to the LHS
what is the rule about acids & conjugate bases?
-a strong acid has a weak conjugate base
-a weak acid has a strong conjugate base
*if an acid readily dissociates, it is unlikely to pick it up again; if it doesnt easily dissociate, the conjugate base will not be very stable & it will readily protonated again
-a strong base has a weak conjugate acid
-a weak base has a strong conjugate acid
describe the acidity of alcohols & phenols
alcohols and phenols are very weal acids; weak dissociation
what is the pKa value for alcohols & phenols
alcohols = 16
phenols = 10
why are phenols more acidic than alcohols?
-the phenoxide anions that result from dissociation are more stable than alkoxide anions
-the -ve charge on an alkoxide ion is concentrated on the oxygen atom, whereas the negative charge on phenoxide ion can be partially delocalised to the 2-, 4- and 6- positions (ortho and para) through resonance
-this stability means that the formation of phenoxide ions is more likely than alkoxide; phenols are stronger acids & have lower pKa values
-this is not possible for alkoxide ions as it is aliphatic
why is the pKa value of 2,2,2,-trifluoroethanol lower than the pKa of ethanol?
-2,2,2,-trifluoroethanol is a stronger acid than ethanol
-this is due to relative stabilities of the alkoxide ions
-in 2,2,2TFE the C-F bonds are all polarised, so that the carbon atom is slightly delta+ve
-on formation of alkoxide ions, the electronegative fluorine atoms can draw some of the anion’s negative charge towards themselves
*inductive effect
-this is not possible in the thoxide ions derived from ethanol
**why is 4-nitrophenol more acidic than phenol
the presence of the nitro group leads to further stabilisation of the phenoxide ion by resonance and inductive effects
-the more stable the phenoxide/alkoxide ion, the more acidic the corresponding phenol/alcohol will be
-nitrogen atom has a partial positive charge and the nitro group is strongly electron-withdrawing. the acidity of 4-nitrophenol is thus increased by an inductive effects
-the negative charge of the phenoxide ions derived is not only stabilised by resonance in the aromatic ring, but also via the oxygen atoms of the nitro group
what do electron-donating groups do to acidity? 
electron-donating groups will reduce acidity
rank the following compounds in order of increasing acidity; 2-chloroethanol, 4-chlorophenrol, 4-methyl phenol, ethanol, phenol
1. Ethanol (least acidic) 2. 2-Chloroethanol 3. 4-Methylphenol 4. PhenoL 5. 4-Chlorophenol (most acidic) -Ethanol and 2-chloroethanol are less acidic because alcohols are not resonance-stabilized. The chloro group slightly increases acidity via induction.
-Phenols are more acidic than alcohols due to resonance stabilization. Within phenols, electron-donating groups (e.g., methyl) reduce acidity, while electron-withdrawing groups (e.g., chloro) increase acidity.
Why do electron-donating groups decrease acidity
-Acidity is determined by the stability of the conjugate base. The more stable the conjugate base, the stronger the acid.
-EDGs, such as alkyl groups or groups with lone pairs (like OCH₃), push electron density toward the conjugate base.
-This increased electron density makes the negative charge on the conjugate base less stable, decreasing its ability to form and reducing the compound’s acidity.
In systems like phenols, an EDG reduces the resonance delocalization of the negative charge in the conjugate base.
are protons bonded to carbons weakly or strongly acidic?
-protons that are bonded to carbon atoms adjacent to carbonyl groups are often very weakly acidic due to resonance stabilisation of ion; the negative charge after removal of a proton can be stabilised by resonance
-particularly is there are other electron-withdrawing groups also bonded to the carbon atom
is phenytoin basic or acidic
phenytoin is weakly acidic due to the N-H groups also bonded between the 2 carbonyl groups
-once the negative charge formed by dissociation of the proton is stabilised by resonance
what is the pKa value for carboxylic acids?
3-5
why are carboxylic acids more acidic than alcohols
-the stability of the anion that is formed on deprotonation is an important factor
-the only difference is the pressure of a carbonyl group in place of a CH2 group
-carbonyl groups are polarised, & the carbon atoms carries partial +ve charge
-this makes it easier for the oxygen atoms to bear a negative charge as the carbonyl groups can help to withdraw some of the -ve charge by induction as well as resonance
—ve charge equally delocalised across the O atoms, anion is more stable
how does the structure of the carboxylic acids effect the acidity
-electron withdrawing groups enhance acidity by an inductive effect - stabilising the negative charge by drawing away electron density
-the C-Cl bond is polarised leading to partial +ve charge on carbon atom
-electrons are thus pulled from the carboxylate end of molecule towards Cl atom
-this has the effect of spreading the -ve charge over more atoms and stabilises the ion; thus greater number of Cl atoms, the greater the effect & the stronger the acid
what type of molecules can pass through biological membranes
-biological membranes are hydrophobic and will only allow the passage of weakly polar, non-charged molecules
-acids therefore pass through the barrier in their unionised form, the pH of a solution either side of the membrane is an important factor
What is the Henderson-Hasselbach equation
pH=pka + log[deprotonated]
[protonated]
what does the pka value tell us?
pka of an acidic functional group tells us how readily the group gives up a proton
pka of a base tells us how readily the CONJUGATE ACID of the base gives up a proton
what happens if the pH is LOWER than pKa
if the pH is LOWER than the pKa, protonation is likely
-acidic compounds will be uncharged (unionised) whereas basic compounds will be positively charged (ionised)
what happens if pH is HIGHER than pKa
if the pH is higher than the pka, deprotonation is likely
-acidic compounds will be negatively charged (ionised) whereas basic compounds will be uncharged (unionised)
what proportion of an oral dose of paracetamol pka=9.5 will be ionised at pH 7.4 
*
how do we estimate what percentage of an acidic drug will be ionised at a given pH?
if pH=pka then [A-]=[HA] & the drug is 50% ionised
an increase in1 unit represents a ten-fold increase in the ratio of concentrations
if the pH is 1 unit higher thank the pka then [A-]=10[HA]
*rule of 9s; difference in 1 unit = one 9 in the answer
what is the pH partition hypothesis?
-drugs like aspirin (pka 3.5) are well absorbed from the proximal end of the s.intestine where it is ph6 even though it is between 99 and 99.9% ionised and so is much less lipid soluble
-Absorption takes place as a consequence of the equilibrium. Less than 1% of the drug is in its unionisedform
and this gets absorbed readily. The equilibrium then adjusts itself so that more unionised drug is produced and gets absorbed and the equilibrium adjusts, producing more unionised drug and so on - this continues until the vast majority of the drug has been absorbd
are amides basic 
no
-nitrogen lone pair is delocalised in 2p orbital; all electrons are in use
What determines the chemistry of amines?
The lone pair of electrons on nitrogen
-the lone pair makes amines both basic (makes bond to H)& nucleophilic (makes bond to electron-deficient atom)
draw the equilibrium between amine and water
*the amine acts as the base & water acts as an acid
what should you compare when comparing the relative strengths of bases? +explain using a primary alkylammonium ion
it is convenient to consider the dissociation constant (Ka) of the conjugate acid
-the larger the Ka (smaller pka), the stronger the R-NH3+ is an acid, or weaker R-NH2 is as a base
-a strong base holds onto a proton tightly so it doesnt readily dissociate & its conjugate acid is weak; a weak base will readily give up a proton after it gets one & so its conjugate acid is strong
the pka of NH4+ is 9.30 & the pka of CH3NH3+ is 10.64
Which is the stronger base -NH3 or CH3NH2
-the conjugate acid of NH3 is NH4+
-the conjugate acid of CH3NH2 is CH3NH3+
-the higher the pka of the conjugate acid is, the weaker the conjugate acid is so the stronger the base
-CH3NH2 is the stronger base