McMurry (Kap.18,0-18,5) - amines, naming amines, basicity of amines and arylamines, biological amines and Henderson hasselbach equation

Question 1

What is the functional group amines?

Answer 1

Amines are organic derivatives of ammonia (NH3) - in the same way alcohols and ethers are organic derivatives of water.

Amines (contain a nitrogen atom, with a lone pair of electrons - making them both basic - because they can donate a pair of electrons - and nucleophilic.

Question 2

What is the definition of nucleophilic?

Answer 2

The term nucleophilic refers to the ability of a species (usually a molecule or ion) to donate an electron pair to an electrophile (an electron-deficient species) in a chemical reaction. A nucleophile is a substance that is “nucleus-loving,” meaning it seeks positively charged or electron-deficient areas and can attack them by donating its electron pair.

Question 3

Does amines occur in living organisms?

Answer 3

Yes widely (se page 646 for examples).

Though amino acids are the building blocks for protein, and cyclic amine bases are constituents of nucleic acids - RNA).

Question 4

There are two types of substitutions to amines, which ones?

Answer 4

Alkyl-substituted amines (alkylamines) (example methyl, ethyl, propyl…)

Aryl-substituted amines (arylamines) (example indgår i en aromatisk ring)

Question 5

Depending on the number of organic substituents connected to nitrogen, they are named differently.

Explain.

Answer 5

Primary nitrogen = RNH2

Secondary nitrogen = R2NH

Tertiary nitrogen = NH3

Depending on number of organic substituents bound to nitrogen.

quaternary ammonium salts = nitrogen carrying four substituents with a formal nitrogen charge (R4N+).

Question 6

Primary amines are named in the IUPAC system in several ways.

Se page 645-647 for naming all types of amines.

Answer 6

see the pages.

Question 7

Is the bonding in alkylamines the same as the bonding in ammonia (NH3)?

Answer 7

Yes - the N is SP3 hybridized, with three substituents occupying three corners of a regular tetrahedron, and the lone pairs occupying the fourth one.

C-N-C bond angles are close to 109 tetrahedral value - 108 in trimethylamine for example.

Question 8

Is a Nitrogen with three different substituents chiral?

Answer 8

Yes and no.

chiral amines`s two enantiomers rapidly interconvert by a “pyramidal inversion” - therefore they are not chiral.

Amines with pyramidal inversion generally do not exhibit stable chirality at room temperature, because the inversion flips the configuration so rapidly that the two enantiomers cannot be separated.

Question 9

When are amines water soluble or not water soluble?

Answer 9

They are determined like alcohols:

1) amines with fewer then 5 carbons = water soluble

2) Because they form hydrogen bonds (like alcohols) - they have higher boiling points then alkanes of similiar weight class.

Question 10

What is the chemistry of amines dominated by?

Answer 10

The lone pairs on the nitrogen (they make amines both basic and nucleophilic).

They react with acids to form acid-base salts anf with electrophiles in many polar reactions.

Question 11

Are amines strong bases?

Answer 11

Stronger bases then alcohols and ethers.

When an amine is dissolved in water, water acts as an acid to transer a proton to the amine.

Question 12

Are Kb values used often?

Answer 12

No. The way Kb is measured is by looking at the Ka/pKa value of the corresponding ammonium ion (acid form), and then find the pKb/Kb out of that (14-pKa = pKb)

Or a strong acid means a weak korresponding base.

Question 13

The base strength is measured by Kb and pKb, explain what is it?

Answer 13

basicity kontant (Kb) = large Kb means stronger base.

Smaller pKb = the stronger the base

(just like pKa and Ka - but with base).

Question 14

The weaker the base (the smaller the pKa value for corresponding acid form - stronger acid)

The stronger the base (the bigger the pKa value for the corresponding acid form - weaker acid).

Answer 14

correct

Question 15

Basicity levels of some common amines, and the pkA values of the corresponding acid forms (see page 650)

Answer 15

see page 650

Question 16

Arylamines (N in ring) are less basic then alkulamines

Answer 16

correct.

Question 17

Amides (RCONH2) - another functional group then amines have other properties. What are they and why?

Answer 17

They are nonbasic. They are not protonated by water, and they are poor nucleophiles.

The reason for this is because amides are stabilized by the delocalization of the nitrogen lone pair electrons through orbital overlap with the carbonyl group. In resonance terms - amides are more stable and less reactive then amines, because they are hybrids of two resonance forms.
(the delocation occurs because of the presence of O atom).

The amide ressonance stabilization is lost when the nitrogen is protonated - therefore it is disfavored.

Question 18

What other properties them being bases can amines have?

Answer 18

Primary and secondary amines can acts as very weak acids (because an N-H proton can be removed by a sufficient strong base).

Question 19

How is the basicity of the arylamines (less then the amines)

Answer 19

They are less basic then the amines because the nitrogen lone pair electrons are delocalized by interactions with the aromatic ring (pi) electron system, and are less available for bonding to H+.

In resonance terms, arylamines are stabilized relative to alkylamines because of their five resonance forms (page 652) - more stable bases gives a weaker base.

Arylamines also have a larger positive (delta G) for protonation and are therefore less basic than alkylamines.

Question 20

Substituted arylamines can either be more or less basic depending on the substituents.

Describe how?

Answer 20

Electron donating substituents (CH3, OCH3) - increase the basicity of the arylamine.

Electron withdrawing substituents (Cl, NO2, CN) - decrease arylamines basicity.

(on page 653 - see the list of electron withdrawing and donating groups).

Question 21

The dissociation of carboxylic acid in (aq) solution buffered to give a pH that can be calculated via the Henderson-Hasselbach equation.

In physiological pH of 7,3 inside living cells, carboxylic acids are almost entirely in their carboxylate anions (RCO2-) - ion form/deprotonated. (the enviroment is more basic then the pKa, therefore in deprotonated form).

Answer 21

correct

Question 22

What about amine bases? in what form do they exist in physiological pH inside cells?

Answer 22

nearly 100% of the methylamine exists in its protonated form as methylammonium ion (because pKa is higher then the pH).

So they nearly always exist in the protonated form in body - also the other types of amines.