Nitrogen and Sulfur Organic Compounds

Question 1

what kind of molecules are amines and from what does it derive from?

Answer 1

organic, ammonia

Question 2

How many lone pairs? Hybridization?

Answer 2

1 lone pair
sp3

Question 3

Amines; Lewis Base

Answer 3

A nucleophile that uses lone pair to form a bond with an electrophile

Question 4

Amines; Brønsted-Lowry Base

Answer 4

Reacting as a nucleophile by accepting a H acid

Question 5

Larger pKa =

Answer 5

stronger base

Question 6

Alkyl amines are typically ______ bases than heterocyclic or aryl amines

Answer 6

stronger

Question 7

What are the Factors Affecting Basicity of Amines?

Answer 7

1. Hybridisation of the Nitrogen: In heterocycles, N is sp2 hybridised. Increasing s-character brings electrons closer to the nucleus, reducing the tendency to bond to a proton, compared to sp3 hybridised nitrogens.
2. Resonance stabilisation: Lone pair shared with the ring in aryl amines (reduced basicity)
3. Inductive Stabilisation: Alkyl groups donate electron to the more electronegative N increasing the electron density of N and making it more basic

Question 8

Reactions of Amines
1) Reaction of Amines with Ketones and Aldehydes

Answer 8

B. Condensations of hydroxylamine and hydrazine with ketones and aldehydes
R2 > Reagent > Deriative name

Question 9

Reactions of Amines
2) Electrophilic Aromatic Substitution of Arylamines

Answer 9

Resonance Stabilisation: There will be lone pair stabilisation by the N lone pair
Attack will be ortho or para to the NH2 group

Question 10

Reactions of Amines
3) Alkylation of Amines by Alkyl Halides

Answer 10

SN2 Mechanism (no 3o halides)
2o halides often give poor yields (elimination predominates over substitution)

2o amine is nucleophilic and it can react with another molecule of the halide

Salt of a 3o amine

Question 11

Reactions of Amines
4) Acylation of Amines by Acid Chlorides
Nucleophilic Acyl Substitution

Answer 11

Step 1: Amine attacks electrophilic carbonyl group to form tetrahedral intermediate

Steps 2+3: Tetrahedral intermediate expels the chloride ion and loss of H. Pyridine and other bases neutralise the HCl produced. Amide does not undergo further acylation as less basic and nucleophilic

Question 12

Reactions of Amines
5) Formation of Sulphonamides

Answer 12

Primary or Secondary Amines

Attack a sulfonyl chloride to yield a sulphonamide

Question 13

Reactions of Amines
6) Hofmann Elimination: Amines to Alkenes

Answer 13

Step 1: Exhaustive methylation of an amine

Step 2: Hofmann Elimination
(E2 reaction using heat and a base, e.g. NaOH)
Least Substituted Alkene is the product (Hofmann Product)

Question 14

Reactions of Amines
7) Oxidation of Amines
** do not need to know > no Curley arrows**

Answer 14

A. Primary Amines: Oxidise easily but results in complex mixture of products

B. secondary Amines

C. tertiary Amines

Question 15

Reactions of Amines
8) Cope Elimination: Amines to Alkenes

Answer 15

Internal Elimination: Yields the least-substituted alkene product

Question 16

Reactions of Amines
9) Diazotization: Using Nitrous acid (NaNO2 mixed with cold, dilute HCl)

Answer 16

hydrolosis > sandmeyer reaction > replacement by fluride or iodide > reduction to hydrogen > diazo coupling

Question 17

Synthesis of Amines
1. Reductive Amination

Answer 17

Adding a primary or secondary alkyl group to an amine

Two-step procedure:
1. Form an imine or oxime derivative of a ketone or aldehyde (and isolate it)
2. Reduce it to an amine

Question 18

Synthesis of amines ; primary, secondary and tertiary

Answer 18

PRIMARY = Reduction with H2 / Ni, LiAlH4 / H2O, or Zn / HCl

SECONDARY = Reduction with NaBH4, or LiAlH4 / H2O

TERTIARY = Reduction with NaBH(OAc)3
Iminium salts are rarely isolated (unstable)

Question 19

Synthesis of Amines
2. Acylation-reduction of amines

Answer 19

Ammonia to 1o amine, 1o amine to 2o amine, or 2o amine to 3o amine
The added alkyl group is always 1o
C=O amide reduced to methylene group (-CH2-)

Question 20

Synthesis of Amines
3. Syntheses Limited to Primary Amines: Alkylation of Ammonia

Answer 20

SN2 Reaction complicated by a tendency for over-alkylation
Large excess of NH3 is required

Phthalimide anion: Protected form of ammonia – cannot alkylate more than once
Also is a strong nucleophile (SN2)

Azide ion (N3-) is an excellent nucleophile
Alkyl azides (RN3) do not have a tendency to react further

Cyanide ion (CN-) is a good SN2 nucleophile
The Nitrile (RCN) has no tendency to react further so converting to the amine needs stronger conditions

Aromatic and aliphatic nitro groups are easily reduced to amino groups

Question 21

Synthesis of Amines
4. Nucleophilic aromatic substitution

Answer 21

The aromatic ring is activated towards a nucleophilic attack (EWG)
NH3 is a strong nucleophile capable of carrying out the attack

powerful electron-withdrawing group

Question 22

Synthesis of Amines
5. Amide Rearrangement (Hofmann Rearrangement)
steps?

Answer 22

slide 33/34

Question 23

Sulfur Containing Compounds

Answer 23

Sulfur (s): p-block element in Group VI – much less electronegative than oxygen

Question 24

Heterocyclic Compounds

Answer 24

Non-Carbon atoms are referred to as Heteroatoms

Cyclic compounds that have one or more of these atoms (N, O, S) = heterocyclic compounds

Many have important roles in medicine or biological systems (Caffeine, cephalosporins, DNA etc)

There are different ring sizes, saturated vs unsaturated, aromatic vs non-aromatic