Aldehydes and Ketones. Flashcards
1
Q
What 2 steps are needed to turn a carboxylic acid into an aldehyde?
A
The carboxylic acid needs to be reduced to a primary alcohol.
The primary alcohol needs to be oxidised to an aldehyde.
2
Q
What are 2 good reagents for the 2 steps of turning a carboxylic acid into an aldehyde?
A
Step 1: LiAlH4, dee, water.
Step 2: PCC, CH2Cl2.
3
Q
What are the 2 steps of turning an aldehyde into a ketone?
A
Aldehyde to secondary alcohol.
Secondary alcohol to ketone.
4
Q
What are the important factors of the cyanohydrin formation?
A
A new carbon-carbon bond is formed.
CN group can be converted to COOH and CH2NH2.
OH group can undergo functional group transformations.
5
Q
What is a hemiacetal formation?
A
OH
I
R-C-H
I
O-R
6
Q
What is an acetal formation?
A
O-R
I
R-C-H
I
O-R
7
Q
What is a hemiketal formation?
A
OH
I
R-C-CH3
I
O-R
8
Q
What is a ketal formation?
A
O-R
I
R-C-CH3
I
O-R
9
Q
What is the Wittig reaction used for?
A
Conversion of aldehydes and ketones to alkenes.
10
Q
What is the Baeyer Williger reaction used for?
A
The oxidation of ketones.
11
Q
Ketones and aldehydes are what kind of group?
A
Carbonyl.
12
Q
The carbonyl carbon has what hybridisation?
A
SP2.
13
Q
In an aldehyde or a ketone what hybridisation is the oxygen?
A
SP2.
14
Q
What are good reagents to turn a secondary alcohol into a ketone?
A
Chromic acid or KMnO4.
15
Q
How can more complicated ketones be made?
A
Complicated ketones can be made by the oxidation of alcohols, which in turn can be made from reaction of a
Grignard and an aldehyde.
16
Q
How are aldehydes made?
A
Aldehydes are made from the oxidation of primary alcohols. This oxidation needs to be done carefully to avoid over-oxidation to carboxylic acids.
17
Q
What is ozonolysis?
A
Alkenes can be cleaved by ozone (followed by a mild reduction) to generate aldehydes and/or ketones.
18
Q
What is an excellent method for the preparation of alkyl aryl ketones?
A
Friedal Crafts acylation.
19
Q
What is dithiane?
A
Dithiane has relatively acidic hydrogens located between the two sulfur atoms.
20
Q
How can the acidic hydrogens be removed from diathiane?
A
These can be removed by a
strong base.
21
Q
How can dithiane anion can react with primary alkyl halides?
A
The dithiane anion can react as a nucleophile with primary alkyl halides, and this alkylation generates a thioacetal.
22
Q
The hydrolysis of a thioacetal generates what?
A
The hydrolysis of a thioacetal generates an aldehyde.
23
Q
How can the thioacetal can be turned to a ketone?
A
The thioacetal can be further deprotonated and reacted with another (different) alkyl halide to
generate a new thioacetal with two alkyl substituents. On hydrolysis, this thioacetal produces a ketone.
24
Q
What is is a good route for the construction of unsymmetrical ketones?
A
The further hydrolysis of a thioacetal.
25
What reagents are very reactive towards carbonyl compounds?
Organolithium reagents.
26
Nitrile groups contain what compounds?
The cyano group (carbon nitrogen triple bond).
27
How do nucleophiles attack the nitrile group?
Since N is more electronegative than C, the triple bond is polarised toward the nitrogen, (similar to the C=O bond).
Therefore nucleophiles can attack the electrophilic carbon of the nitrile group.
28
How do Grignard reagents attack the nitrile group?
Grignard (or organolithium) reagents attack the nitrile to generate the magnesium (or lithium) salt of an imine.
Acid hydrolysis generates the imine, and under these acidic conditions, the imine is hydrolyzed to a ketone.
29
What are carboxylic acids often converted into in order to make it easier to reduce them into an aldehyde?
An acid chloride.
30
What will reduce acid chlorides to aldehydes?
Although strong reducing agents like LiAlH4 still reduce acid chlorides all the way to primary alcohols, milder
reducing agents like lithium aluminum tri(t
butoxy) hydride can selectively reduce acid chlorides to aldehydes.
31
Do acid chlorides react with Grignard (and organolithium) reagents
Yes.
32
What do we react an acid chloride with in order to form a ketone?
Lithium dialkylcuprate (R2-Cu-Li).
33
How is the lithium dialkyl cuprate produced?
The lithium dialkyl cuprate is produced by the reaction of two equivalents of the organolithium reagent with
copper (I) iodide.
2 R-Li + CuI = R2CuLi + LiI
34
What is the most common reaction of aldehydes and ketones?
Nucleophilic addition.
35
What usually happens in a nucleophilic addition reaction on an aldehyde or a ketone?
This is usually the addition of a nucleophile and a proton across the C=O double bond.
36
What happens when the nucleophile attacks the carbonyl group in a nucleophilic addition reaction?
As the nucleophile attacks the carbonyl group, the carbon atom changes from sp2
to sp3
The electrons of the pi bond are pushed out onto the oxygen, generating an alkoxide anion.
Protonation of this anion gives the final product.
37
To turn a hydride into a ketone what is used?
A strong nucleophile.
38
What happens to the carbonyl in acidic solution?
The carbonyl group is a weak base, and in acidic solution it can become protonated.
This makes the carbon very electrophilic (see resonance structures), and so it will react with poor nucleophiles.
39
The base catalysed addition reactions to carbonyl compounds result from what?
The base catalysed addition reactions to carbonyl compounds result from initial attack of a strong nucleophile, whereas the acid catalysed reactions begin with the protonation of the oxygen, followed by attack of the weaker
nucleophile.
40
Are aldehydes or ketones more reactive?
Aldehydes are more reactive than ketones.
41
Why are aldehydes more reactive than ketones?
Ketones have two alkyl substituents whereas aldehydes only have one.
42
Why do carbonyls undergo reactions with nucleophiles?
Carbonyl compounds undergo reaction with nucleophiles because of the polarisation of the C=O bond.
43
Why do ketones have their partial positive charge reduced more than aldehydes?
Alkyl groups are electron donating, and so ketones have their effective partial positive charge reduced more than
aldehydes (two alkyl substituents vs. one alkyl substituent).
44
Which carbon is the site that the nucleophile must approach for the reaction to occur?
The electrophilic carbon is the site that the nucleophile must approach for reaction to occur.
45
Why do ketones offer more steric resistance to nucleophilic attack?
In ketones the two alkyl substituents create more steric hindrance than the single substituent that aldehydes have.
46
What is the phosphorus stabilised anion called in the Wittig reaction?
The phosphorus stabilised anion is called an YLIDE, which is a molecule that is overall neutral, but exists as a
carbanion bound to a positively charged heteroatom.
47
How are phosphorus ylides produced?
Phosphorus ylides are produced from the reaction of triphenylphosphine and alkyl halides.
48
The wittig reaction is a good source of what?
This is a good general route to make new C=C double bonds starting from carbonyl compounds.
Alkenes.
49
How many steps are in a Wittig reaction?
2.
50
What are the 2 steps in a Wittig reaction?
This reaction starts with the nucleophilic attack of the Phosphorus on the alkyl halide. This generates an alkyl triphenylphosphonium salt. Treatment of this salt with a strong base removes a proton from the carbon bound to the phosphorus, and generates
the ylide.
The carbanionic character of the ylide makes it a very powerful nucleophile, and so it reacts rapidly with a
carbonyl group.
This produces an intermediate which has charge separation - a betaine.
Betaines are unusual since they have a negatively charged oxygen and a positively charged phosphorus.
Phosphorus and oxygen always form strong bonds, and these groups combine to generate a four membered ring - an oxaphosphetane ring. This 4 membered ring quickly collapses to generate an alkene and (very stable) triphenyl phosphine oxide.
51
What is the driving force of the Wittig reaction?
The elimination of Ph3P=O is the driving force of this reaction.
52
What is the strategy of the Wittig reaction?
By dividing a target molecule at the double bond, you can decide which of the two components should best come
from the carbonyl, and which from the ylide.
53
From what kind of alkyl halide does the ylide usually come from?
In general, the ylide should come from an unhindered alkyl halide since triphenyl phosphine is so bulky.
A primary one.
54
How does the hydration of ketones happen?
Hydration proceeds through the two classic nucleophilic addition mechanisms with water (in acid) or hydroxide (in
base) acting as the nucleophile.
55
In acidic conditions how does hydration of a ketone occur?
Acidic Conditions – Protonation followed by nucleophile attack.
56
In basic conditions how does hydration of a ketone occur?
Basic Conditions – Nucleophile attack followed by protonation
57
Are ketones or aldehydes more likely to form hydrates?
Aldehydes.
58
Why are aldehydes more likely to form hydrates?
Aldehydes are more likely to form hydrates since they have the larger partial positive charge on the carbonyl
carbon (larger charge = less stable = more reactive).
59
Is cyanide a good nucleophile?
Cyanide is a strong base (HCN weak acid) and a good nucleophile.
60
How does cyanide react with carbonyls?
Cyanide reacts rapidly with carbonyl compounds producing cyanohydrins, via the base catalyzed nucleophilic addition mechanism.
61
What is an imine?
An imine is a nitrogen analogue of a ketone (or aldehyde) with a C=N nitrogen double bond instead of a C=O.
62
How are imines generated?
Under appropriate conditions, primary amines (and ammonia) react with ketones or aldehydes to generate imines.
63
Are imnines nucleophilic?
Just as amines are nucleophilic and basic, so are imines.
64
Imine formation is an example of what kind of reaction?
Imine formation is an example of a condensation reaction - where two molecules join together accompanied by the
expulsion of a small molecule (usually water).
65
What are the steps of imine formation?
The mechanism of imine formation starts with the addition of the amine to the carbonyl group.
Protonation of the oxyanion and deprotonation of the nitrogen cation generates an unstable intermediate called a carbinolamine.
The carbinolamine has its oxygen protonated, and then water acts as the good leaving group. This acid catalyzed dehydration creates the double bond, and the last step is the removal of the proton to produce
the neutral amine product.
66
What is the best pH for imine formation?
The best pH for imine formation is around 4.5.
67
What are produced when hydroxylamines are reacted with aldehydes and ketones.
Oximes.
68
What are produced through reaction of hydrazines with aldehydes and ketones.
Hydrazones.
69
What are formed from reaction with semicarbazides?
Semicarbazones.
70
How are acetals formed?
In a similar fashion to the formation of hydrates with water, aldehydes and ketones form acetals through reaction with alcohols.
71
How are acetals formed?
In the formation of an acetal, two molecules of alcohol add to the carbonyl group, and one mole of water is
eliminated.
72
Acetal formation only occurs with what?
Acetal formation only occurs with acid catalysis.
73
What are the steps of an acetal formation?
The first step is the typical acid catalysed addition to the carbonyl group.
The hemiacetal reacts further to produce the more stable acetal: The second half of the mechanism starts with protonation of the hydroxyl group, followed by its leaving.
The carbocation thus generated is resonance stabilized, and attack of the alcohol, after proton loss, produces the
final acetal.
The second step (and therefore overall transformation) requires the acidic conditions to aid the replacement of the hydroxyl group (-OH is a bad leaving group, yet -OH2
+) is a good leaving group.
74
How are cyclic acetals produced?
More commonly, instead of two molecules of alcohols being used, a diol is used (entropically more favorable).
This produces cyclic acetals.
75
What is usually the diol of choice for producing cyclic acetals?
More commonly, instead of two molecules of alcohols being used, a diol is used (entropically more favourable).
This produces cyclic acetals.
76
What can be used to 'protect' aldehydes and ketones from reacting with strong bases and nucleophiles?
Acetals.
77
What can be used to oxidise aldehydes?
Chromic acid, permanganate etc.
78
What are aldehydes oxidised too?
Carboxylic acid.
79
Aldehydes and ketones are most commonly reduced by what?
Aldehydes and ketones are most commonly reduced by sodium borohydride.
80
What is catalytic hydrogenation?
Just as C=C double bonds can be reduced by the addition of hydrogen across the double bond, so can C=O double bonds.
81
What kind of odours do aldehydes have?
Pungent odours. Vanillin and cinnamaldehyde.
82
What kind of odours do ketones have?
sweet odors. Carvone and camphor (spearmint and caraway seeds)
83
What is ketosis?
Pathological condition whereby the body produces more acetoacetate than can be metabolized - excess is broken down to acetone and CO2 (sweet smell on breath)
84
How do male and female sex hormones differ?
Progesterone (female) and testosterone (male) differ in the presence of an acetyl group versus a hydroxide
85
If a Grignard reagent reacts with a ketone what results?
A tertiary alcohol.
86
If a Grignard reagent reacts with an aldehyde what results?
A secondary alcohol.
87
If a Grignard reagent reacts with a carbon dioxide what results?
Reaction with carbon dioxide yields a carboxylic acid one carbon longer than Grignard reagent!
88
Why is order of addition important when dealing with Grignards?
Order of addition is important - acid is not added until after the Grignard reagent has been allowed to react with the carbonyl.
89
What are the 2 reactions that take place between a Grignard and an ester?
Reaction I - there is a group that can be displaced by a good Nu: - nucleophilic acyl substitution reaction - generation of a ketone.
Reaction II - no longer have a group that can be displaced by a good Nu: - nucleophilic addition reaction - generation of a tertiary alcohol.
90
What are the 3 steps in the reaction that takes place between a Grignard and an ester?
Step 1 - Nu: attack generates TI that can decompose - ketone.
Step 2 - Nu: attack (ketones are more reactive than esters!) generates TI that cannot decompose - alkoxide ion.
Step 3 - protonation - 3° alcohol.
91
What is formed when a Grignard reacts with an acyl chloride?
Reaction I - generates a ketone (less reactive than acyl halide!)
Then a tertiary alcohol will be formed as a ketone is a powerful nucleophile.
92
What is a hydride ion?
Hydrogen with a lone pair of electrons.
93
What is special about hydride ions?
Hydride ions are strongly basic - Nu: as strong base without a lone pair of electrons - nucleophilic addition reaction.
94
What are the 2 steps when hydride ions react with ketones and aldehydes?
Step 1 - attack of Nu: on carbonyl carbon forming an alkoxide intermediate - addition of first H atom.
Step 2 - protonates of the alkoxide generates the product alcohol - addition of second H atom.
95
Reacting hydride ions with a carbonyl adds what?
The overall reaction adds H2 to the carbonyl group.
96
Adding hydride ions is what kind of reaction?
A reduction reaction.
97
What is a common source of a hydride ion?
NaBH4.
98
NaBH4 with an aldehyde produces what?
Primary alcohol.
99
NaBH4 with a ketone produces what?
Secondary alcohol.
100
What is an acyl or acid chloride?
O
II
R-C-Cl
101
What are the 2 reactions when NaBH4 reacts with an acyl chloride?
Reaction I - there is a group that can be displaced by a good Nu: - nucleophilic acyl substitution reaction - generation of an aldehyde.
Reaction II - no longer have a group that can be displaced by a good Nu: - nucleophilic addition reaction - generation of a primary alcohol.
102
What are the 3 steps of the reaction when NaBH4 reacts with an acyl chloride?
Step 1 - Nu: attack generates TI that can decompose - aldehyde.
Step 2 - Nu: attack generates TI that cannot decompose - alkoxide ion.
Step 3 - protonation - 1° alcohol.
103
Acyl chlorides and NaBH4 produces what?
A primary alcohol.
104
Which is a more reactive hydride donor NaBH4 or LiAlH4?
LiAlH4.
105
What are the 2 reactions when LiAlH4 reacts with an ester?
Reaction I - esters are not as reactive as aldehydes and ketones, and require a more reactive hydride donor (LiAlH4) - generation of an aldehyde.
Reaction II - generation of TWO alcohols (from acyl and alkyl portions).
106
What are the 3 steps of the reaction when LiAlH4 reacts with an ester?
Step 1 - Nu: attack generates TI that can decompose - aldehyde.
Step 2 - Nu: attack generates TI that cannot decompose - alkoxide ion.
Step 3 - protonation generates alcohols - 1° ROH (from acyl), and other from alkyl portion.
107
What are is the final product when LiAlH4 reacts with an ester?
A primary alcohol.
108
What are the 2 reactions when a hydride ion reacts with a carboxylic acid?
Reaction I - carboxylic acids also require LiAlH4 - generation of an aldehyde.
Reaction II - generation of a single primary alcohol.
109
What are the 3 steps of the reaction when a hydride ion reacts with a carboxylic acid?
Step 1 - Hydride (base!) deprotonates - H2 and carboxylate.
Step 2 - AlH3 forms complex with carboxylate - carboxylate ions are not suitable electrophiles for Nu: attack.
Steps 3 - 5 - Analogous to ester reduction by LiAlH4, two additions of hydride occur generating an aldehyde first that becomes a primary alcohol.
110
What is formed when a hydride ion reacts with a carboxylic acid?
A primary alcohol.
111
Is the cyanide ion an acid or a nucleophile?
Hydrogen cyanide - HCN is an acid while the cyanide ion is a Nu.
112
What are the 2 steps when a cyanide ion attacks a carbonyl?
Step 1 - attack of Nu: (cyanide ion) on carbonyl carbon forming an alkoxide intermediate.
Step 2 - hydrogen cyanide serves as the acid to protonate the alkoxide forming the product cyanohydrin.
113
When cyanide is reacted with a carbonyl what is the final product?
Acetone cyanohydrin.
114
What are amines?
R-NH2. (Primary amine.)
R-NH-R. (Secondary amine.)
115
When secondary amines react with a carbonyl what is the final product?
Secondary amines - reaction generates an enamine (alkene + amine) with double bond between carbon atoms.
116
What is an enamine?
```
R
I
R-C=C-N
I
R
```
117
When primary amines react with a carbonyl what is the final product?
An imine. (A Schiff base.)
118
What is an imine?
R-C=N-R
119
What is reductive amination?
Reductive amination (using ammonia) - reaction of an aldehyde or ketone with excess ammonia in the presence of a reducing agent.
120
What are the 2 reactions when ammonia reacts with a carbonyl?
Reaction 1 - ammonia + carbonyl compound yields an unstable (reactive) imine.
Reaction 2 - reduction of C=N double bond by H2, Pd/C gives a primary amine.
121
What happens when a carbonyl is reacted with hydroxylamine?
Using hydroxylamine - reaction of an aldehyde or ketone with hydroxylamine (generating oxime) in the presence of a reducing agent generates primary amines
122
What are the 2 reactions when a carbonyl reacts with a hydroxylamine?
Reaction 1 - hydroxylamine + carbonyl compound yields stable oxime.
Reaction 2 - reduction of C=N double bond by H2, Pd/C gives a primary amine.
123
When carbonyls react with hydroxalymine or ammonia, what is formed?
A primary amine.
124
What is an acid catalysed reaction?
Acid-catalysed reaction - water is a poor Nu:, so electrophilicity of the carbonyl carbon is increased by protonation of the carbonyl oxygen.
125
What are Gem diols?
Gem-diols (hydrates) - molecules containing two OH groups on the same carbon atom - generated by the hydration of ketones and aldehydes.
126
What does a catalyst do?
It increases the rate of a reaction, not the distribution of products (thermodynamics).
127
What is generated if a carbonyl reacts with water?
A Gem diol.
128
What is an acetal?
Molecules containing two OR groups on the same carbon atom - generated by the reaction of an aldehyde with 2 equivalents of alcohol (a hemiacetal is first generated by the addition of 1 equivalent of alcohol).
129
What is a ketal?
Ketal - molecules containing two OR groups on the same carbon atom - generated by the reaction of a ketone with 2 equivalents of alcohol (a hemiketal is first generated by the addition of 1 equivalent of alcohol).
130
Reacting alcohol with carbonyls generates what?
Acetals and Ketals.
131
What is the Wittig reaction?
Wittig reaction - reaction of an aldehyde or a ketone with a phosphonium ylide generates and alkenes.
132
What is an Ylide?
Ylide - compound that has opposite charges on adjacent covalently bonded atoms with complete octets.
133
Carbons on a carbonyl have what hybridisation?
SP2.
134
Do ketones and aldehydes have a higher boiling point than comparable alkanes or ethers?
Yes.
Ketones and aldehydes are more polar, so they have a higher boiling point than comparable alkanes or ethers.
135
Can ketones and aldehydes form hydrogen bonds and how does this property affect their boiling point?
They cannot hydrogen-bond to each other, so their boiling point is lower than comparable alcohol.
136
Ketones and aldehydes are a good solvent for what?
Alcohols.
137
The lone pair of electrons on oxygen of carbonyl can accept what?
Lone pair of electrons on oxygen of carbonyl can accept a hydrogen bond from O—H or
N—H.
138
Which carbonyls are important solvents?
Acetone and methyl ethyl ketone are important solvents.
139
Secondary alcohols are oxidised to what?
Ketones.
140
If an internal alkyne is hyrdrated what is the product?
A ketone.
141
Which reducing agent reacts faster with acid chlorides than with aldehydes?
LiAlH4.
142
What does a Gilman reagent do?
A lithium dialkylcuprate (Gilman reagent) will transfer one of its alkyl groups to the acid chloride.
143
What happens when a carbonyl experiences a nucleophilic addition reaction?
A strong nucleophile attacks the carbonyl carbon, forming an alkoxide ion that is then protonated.
144
How can acetals act as protonating groups?
The acetal will not react with NaBH4, so only the ketone will get reduced.
Hydrolysis conditions will protonate the alcohol and remove the acetal to restore the aldehyde.
145
What does sodium borohydride do?
Sodium borohydride, NaBH4, can reduce ketones to secondary alcohols and aldehydes to primary alcohols.
146
What does lithium aluminium hydride do?
Lithium aluminum hydride, LiAlH4, is a powerful reducing agent, so it can also reduce carboxylic acids and their derivatives.
147
What does hydrogenation with a catalyst do?
Hydrogenation with a catalyst can reduce the carbonyl, but it will also reduce any double or triple bonds present in the molecule.
