Ch 11 Reactions of Alcohols Flashcards
1
Q
dehydration of an alcohol produces what product(s)?
A
alkenes
2
Q
oxidation of an alcohol produces what product(s)?
A
ketones, aldehydes, acids (ex: carboxylic acid)
3
Q
substitution of an alcohol produces what product(s)?
A
halides
(R-X)
4
Q
reduction of an alcohol produces what product(s)?
A
alkanes
(R-H)
5
Q
esterification of an alcohol produces what product(s)?
A
esters
(R-O-C(=O)-R’)
6
Q
tosylation of an alcohol produces what product(s)?
A
tosylate esters
(R-OTs)
(a good leaving group)
7
Q
deprotination of an alcohol (R-OH) to form an alkoxide and treatment with an alkyl halide (R’-X) produces what product(s)?
A
ethers
(R-O-R’)
8
Q
give examples of oxidation based on the change of the formula of the substance:
A
addition of O or O2; addition of X2 (halogens); loss of H2
9
Q
give examples of reduction based on the change of the formula of the substance:
A
addition of H2 (or H-); loss of O or O2; loss of X2
10
Q
give examples of changes in formula of the substance which are condisered neither oxidation nor reduction:
A
addition or loss of H+, -OH, H2O, HX
(more options possible)
11
Q
what does oxidation normally do in terms of bonded atoms to carbon?
A
generally converts C-H bonds to C-O bonds
12
Q
what species is more oxidised, an alkane or a carboxylic acid?
A
carboxylic acid
13
Q
what species is more oxidised, an alkane or a ketone?
A
ketone
14
Q
what species is more oxidised, an alkane or an aldehyde?
A
aldehyde
15
Q
what species is more oxidised, an alkane or a primary alcohol?
A
primary alcohol
16
Q
what species is more oxidised, an alkane or a secondary alcohol?
A
17
Q
what species is more oxidised, a primary alcohol or an aldehyde?
A
aldehyde
18
Q
what species is more oxidised, an aldehyde or a carboxylic acid?
A
carboxylic acid
19
Q
what species is more oxidised, a secondary alcohol or a ketone?
A
ketone
20
Q
what species is more oxidised, a primary alcohol or a carboxylic acid?
A
carboxylic acid
21
Q
classify the groups formed form the oxidation of an alkane from most reduced to most oxidised, starting with a 1° carbon
A
alkane, primary alcohol, aldehyde, carboxylic acid
22
Q
classify the groups formed form the oxidation of an alkane from most reduced to most oxidised, starting with a 2° carbon
A
alkane, secondary alcohol, ketone
23
Q
classify the groups formed form the oxidation of an alkane from most reduced to most oxidised, starting with a 3° carbon
A
alkane, tertiary alcohol
24
Q
what do most alcohol oxidising agents have in common, and how do they work?
A
all have an element (ex: Cr, Cl, I, S) in a high oxidation state bonded to oxygen. The mechanisms are also similar, the first step an intermediate forms in which the oxidant element becomes bound to the alcohol’s oxygen, and after a base removes a proton from the carbinol carbon atom a double bond forms to oxygen, resulting in a oxydised alcohol (a ketone or aldehyde) and a reduced oxidant.
25
why is it difficult to obtain an aldehyde?
most oxidising agents strong enough to oxidise primary alcohols are also strong enough to oxidise aldehydes. pyridinium chlorochromate (CrO3•pyridine•HCl *or* pyH+ CrO3Cl- *or * **PCC**) is a notable exception, capable of oxidising primary alcohols to aldehydes.
26
under what circumstances can tertiary alcohols be oxidised?
breaking of carbon-carbon bonds is required
27
in an aqueous reaction, hypochlorous acid (ClOH) acts as an oxidant. what is its final (reduced) form?
hydronium ( H3O+ ) and chloride ion ( Cl- )
28
chromic acid reagent
**Na2Cr2O7** / H2SO4
sodium dichromate / sulfuric acid in aqueous solution
**CrO3** / H2SO4
chromium trioxide / sulfuric acid in aqueous solution
29
what does the chromic acid reagent do to secondary alcohols?
oxidation of secondary alcohols to **ketones**
30
the **chromic acid (H2CrO4) reagent** is used to oxidise secondary alcohols to ketones and primary alcohols to carboxcylic acids
31
the **chromic acid (H2CrO4) reagent** is used to oxidise secondary alcohols to ketones and primary alcohols to carboxcylic acids
32
the **chromic acid (H2CrO4) reagent** is used to oxidise primary alcohols to carboxylic acids and secondary alcohols to ketones
33
chromic acid test
the chromic acid reagent does not oxidise teritary alcohols, ketones, or alkenes, as that would require breaking carbon-carbon bonds. the colour change from orange to green/blue indicates the presence of primary and secondary alcohols
34
what reagent(s) convert(s) primary alcohols to carboxcylic acids?
chromic acid (H2CrO4), sodium hypochlorite (NaOCl)
35
what reagent(s) convert(s) primary alcohols to aldehydes?
pyridinium chlorochromate (PCC), Swern, DMP
36
which is a stronger oxidising agent, pyridinium chlorochromate (PCC) or the chromic acid reagent (CrO3 / H2SO4)?
the chromic acid reagent (CrO3 / H2SO4), it oxidises primary alcohols to carboxcylic acids
37
Collins reagent
an milder version of the **chromic acid reagent**, diluted chromic acid (H2CrO4) in acetone ((CH3)2CO), also converts primary alcohols to acids and secondary alcohols to ketones
38
Jones reagent
**Jones reagent** is the precursor to **PCC** (pyridinium chlorochromate), which is capable of oxidising primary alcohols to aldehydes
39
household bleach
sodium hypochlorite (NaOCl), oxidations using sodium hypochlorite involve mildly acidic or basic conditions that may be better than chromic acid for acid-sensitive compounds while accomplishing the same task, oxidation of secondary alcohols to ketones and primary alcohols to caboxcylic acids
40
NaOCl
sodium hypochlorite (household bleach), oxidations involve mildly acidic or basic conditions that may be better than chromic acid for acid-sensitive compounds while accomplishing the same task, oxidation of secondary alcohols to ketones and primary alcohols to carboxcylic acids
41
sodium hypochlorite
sodium hypochlorite (NaOCl) (household bleach), oxidations involve mildly acidic or basic conditions that may be better than chromic acid for acid-sensitive compounds while accomplishing the same task, oxidation of secondary alcohols to ketones and primary alcohols to carboxcylic acids
42
sodium hypochlorate (NaOCl), oxidations involve mildly acidic or basic conditions that may be better than chromic acid for acid-sensitive compounds while accomplishing the same task, oxidation of secondary alcohols to ketones and primary alcohols to carboxcylic acids
43
Swern
The *Swern oxidation* uses **dimethyl sulfoxide (DMSO)** as the oxidizing agent to convert alcohols to ketones and aldehydes. **DMSO** and oxalyl chloride ((COCl)2) are added to the alcohol at low temperature, followed by a hindered base such as triethylamine
44
DMSO
The *Swern oxidation* uses **dimethyl sulfoxide (DMSO)** as the oxidizing agent to convert alcohols to ketones and aldehydes. **DMSO** and oxalyl chloride ((COCl)2) are added to the alcohol at low temperature, followed by a hindered base such as triethylamine
45
The *Swern oxidation* uses **dimethyl sulfoxide (DMSO)** as the oxidizing agent to convert alcohols to ketones and aldehydes. **DMSO** and oxalyl chloride ((COCl)2) are added to the alcohol at low temperature, followed by a hindered base such as triethylamine
46
List every reagent capable of oxidising secondary alcohols to ketones
PCC, Swern, Collins, Jones, NaOCl, chromic acid, DMP
47
why are alcohols such versatile chemical intermediates?
they react as both nucleophiles and electrophiles
48
explain this generic alcohol reaction
alcohol reacting as a weak nucleophile, bonding to a strong electrophile (the carbocation)
49
what is the purpose of this reaction of alcohol?
an alcohol (a weak nucleophile) is easily converted to a strong nucleophile by forming its alkoxide ion, so the alkoxide ion can attack a weaker electrophile, such as an alkyl halide
50
in terms of bond cleavage, what is the difference between alcohol reacting as a nucleophile or electrophile?
The O-H bond is broken when alcohols react as nucleophiles, both when an alcohol reacts as a weak nucleophile, or when an alcohol is converted to its alkoxide that then reacts as a strong nucleophile. In contrast, when an alcohol reacts as an electrophile, the C-O bond is broken.
51
describe the effect of the number of hydrogen atoms attatched to oxygen in an alcohol on its action as a nucleophile or an electrophile
alcohol is a poor electrophile/nucleophile. Protonation of alcohol makes it a better leaving group, increasing electrophilicity of the alcohol. Deprotonation of alcohol increases the nucleophilicity of the alcohol.
(nucleophile) R-O- \> R-OH \> R-OH2+ (electrophile)
52
what is the drawback of protonation of an alcohol to form a better electrophile?
The disadvantage of using a protonated alcohol is that a strongly acidic solution is required to protonate the alcohol. Although halide ions are stable in acid, few other good nucleophiles are stable in strongly acidic solutions. Most strong nucleophiles are also basic and will abstract a proton in acid. Once protonated, the reagent is no longer nucleophilic. For example, an acetylide ion would instantly become protonated if it were added to a protonated alcohol.
53
How can we convert an alcohol to an electrophile that is compatible with basic nucleophiles?
convert it to an alkyl halide or tosylate ester (R-OTs)
54
R-OH + TsOH -\>
R-OTs + H2O
55
R-OTs + -OH -\>
alcohol
R-OH + -OTs
56
R-OTs + -C_=_N (cyanide) -\>
nitrile
R-C_=_NR + -OTs
57
R-OTs + X- (halide ion) -\>
alkyl halide
R-X + -OTs
58
R-OTs + R'-O- (alkoxide) -\>
ether
R-O-R + -OTs
59
R-OTs + :NH3 (ammonia) -\>
amine salt
R-NH3+ -OTs
60
R-OH +LiAlH4 -\>
alkane
R-H + -OTs
61
describe the process(es) capable of performing this reaction:
We can reduce an alcohol in two steps, by dehydrating it to an alkene, then hydrogenating the alkene (shown).
Or, convert the alcohol to the tosylate ester, then use a hydride reducing agent to displace the tosylate leaving group (works with most primary and secondary alcohols).
62
describe an alcohol in acid
In acidic solution, an alcohol is in equilibrium with its protonated form. Protonation converts the hydroxyl group from a poor leaving group (-OH) to a good leaving group (H2O). Once the alcohol is protonated, all the usual substitution and elimination reactions are feasible, depending on the structure (1°, 2°, 3°) of the alcohol.
63
what is unique about halide ions as nucelophiles?
Most good nucleophiles are basic, becoming protonated and losing their nucleophilicity in acidic solutions. Halide ions are exceptions, however. Halides are anions of strong acids, so they are weak bases. Solutions of HBr, HCl, or HI contain nucleophilic Br-, Cl-, or I- ions. These acids are commonly used to convert alcohols to the corresponding alkyl halides.
64
how would you convert a tertiary alcohol to a tertiary alkyl halide?
Via SN1. Because alkyl halides are strong nucelophiles but also stable in acid (because they are the weak bases (X-) of strong acids (HX)), protonation of the alcohol forms the leaving group, and carbocation forms (SN1). Halide ion attacks the carbocation. Shifts possible, the carbocation will form on the most substituted carbon.
65
how would you convert a primary alcohol to a primary alkyl halide?
Via SN2. Because alkyl halides are strong nucelophiles but also stable in acid (because they are the weak bases (X-) of strong acids (HX)), protonation of the alcohol forms the leaving group, which is displaced in a concerted mechanism by the halide with inversion of stereochemistry at the alcohol carbon.
66
how would you convert a secondary alcohol to a secondary alkyl halide?
Usually via the SN1 mechanism (competes with SN2), because alkyl halides are strong nucelophiles but also stable in acid (because they are the weak bases (X-) of strong acids (HX)), protonation of the alcohol forms the leaving group, halide ion attacks the carbocation.
67
which is a stronger nucleophile, chloride ion or bromide ion, and why?
Chloride ion is a weaker nucleophile than bromide ion, because it is smaller and less polarisable. An additional Lewis acid, such as zinc chloride (ZnCl2), is sometimes necessary to promote the reaction of HCl with primary and secondary alcohols. Zinc chloride coordinates with the oxygen of the alcohol in the same way a proton does— except that zinc chloride coordinates more strongly.
The reagent composed of HCl and ZnCl2 is called the **Lucas reagent**. Secondary and tertiary alcohols react with the Lucas reagent by the SN1 mechanism.
68
What is the order of reaction and relative rate for primary, secondary and tertiary alcohols with the Lucas reagent (ZnCl2)?
**Lucas reagent (ZnCl2)** forms an excellent leaving group, and so favours SN1 mechanism, tertiarty alcohols react fastest, followed by secondary alcohols. Primary alcohols cannot form the carbocation and must wait to be attacked via SN2, which in this case is much slower.
69
The reactions of alcohols with hydrohalic acids do not always give good yields of the expected alkyl halides. Why?
1. *Poor yields of alkyl chlorides from primary and secondary alcohols.* Primary and secondary alcohols react with HCl much more slowly than tertiary alcohols, even with zinc chloride added. Under these conditions, side reactions may prevent good yields of the alkyl halides.
2. *Eliminations.* Heating an alcohol in a concentrated acid such as HCl or HBr often leads to **elimination**. Once the hydroxyl group of the alcohol has been protonated and converted to a good leaving group, it becomes a candidate for both **substitution** and **elimination**.
3. *Rearrangements*. Carbocation intermediates are always prone to **rearrangements**. We have seen that hydrogen atoms and alkyl groups can migrate from one carbon atom to another to form a more stable carbocation. This rearrangement may occur as the leaving group leaves, or it may occur once the cation has formed.
4. *Limited ability to make alkyl iodides*. Many alcohols do not react with HI to give acceptable yields of alkyl iodides. Alkyl iodides are valuable intermediates, however, because iodides are the most reactive of the alkyl halides. Instead, several phosphorus halides are useful for converting alcohols to alkyl halides: Phosphorus tribromide (PBr3), phosphorus trichloride (PCl3), and phosphorus pentachloride (PCl5).
70
What is the purpose of the phosphorous halide reagent?
To convert primary and secondary alchols to alkyl halides via SN2 (inversion of stereochemistry), also works with **iodine**, _unlike_ hydrohalic acids (R-OH + HX -\> R-X + H2O). Does not work with tertiary alcohols.
71
what mechanism do alcohol dehydrations generally take place via?
Alcohol dehydrations generally take place through the E1 mechanism. In the acid-catalysed dehydration of an alcohol, protonation of the hydroxyl group converts it to a good leaving group. Water leaves, forming a carbocation. Loss of a proton gives the alkene.
72
what is the rate limiting step in the acid-catalysed dehydration of an alcohol?
73
describe the acid-catalysed dehydration of a primary alcohol
With primary alcohols, rearrangement and isomerization of the products are so common that acid-catalysed dehydration is rarely a good method for converting them to alkenes. The following mechanism shows how butan-1-ol undergoes dehydration with rearrangement to give a mixture of but-1-ene and but-2-ene. The more highly substituted product, but-2-ene, is the major product, in accordance with the Zaitsev rule.
74
outline the guidelines for predicting products from of acid-catalysed dehydration.
1. Dehydration usually goes by the E1 mechanism. Rearrangements may occur to form more stable carbocations.
2. Dehydration works best with tertiary alcohols and almost as well with secondary alcohols. Rearrangements and poor yields are common with primary alcohols.
3. (Zaitsev’s rule) If two or more alkenes might be formed by deprotonation of the carbocation, the most substituted alkene usually predominates.
75
What does presence of a strong acid or a reactant that can dissociate to give a strong electrophile indicate about the type of mechanism involved?
In the presence of a strong acid or a reactant that can dissociate to give a strong electrophile, the mechanism probably involves strong electrophiles as intermediates. Acid-catalyzed reactions and reactions involving carbocations (such as the SN1, the E1, and most alcohol dehydrations) fall into this category.
76
What is the first step in determining what mechanism to use?
First, determine what kinds of conditions and catalysts are involved. In general, reactions may be classified as involving (a) strong electrophiles (including acid-catalyzed reactions), (b) strong nucleophiles (including base-catalyzed reactions), or (c) free radicals. These three types of mechanisms are quite distinct, and you should first try to determine which type is involved.
77
What does presence of a strong base or a strong nucleophile indicate about the type of mechanism involved?
In the presence of a strong base or a strong nucleophile, the mechanism probably involves strong nucleophiles as intermediates. Base-catalyzed reactions and those depending on base strength (such as the SN2 and the E2) generally fall into this category.
78
How can you determine if a free-radical is involved in a reaction?
Free-radical reactions usually require a free-radical initiator such as chlorine, bromine, NBS, or a peroxide. In most free-radical reactions, there is no need for a strong acid or base.
79
Explain the environment and allowable species in reactions involving strong electrophiles
When a strong acid or electrophile is present, expect to see intermediates that are strong acids and strong electrophiles. Cationic intermediates are common. Bases and nucleophiles in such a reaction are generally weak, however. Avoid drawing carbanions, hydroxide ions, alkoxide ions, and other strong bases. They are unlikely to co-exist with strong acids and strong electrophiles.
Functional groups are often converted to carbocations or other strong electrophiles by protonation or reaction with a strong electrophile. Then the carbocation or other strong electrophile reacts with a weak nucleophile such as an alkene or the solvent.
80
osmium tetroxide (OsO4) and peroxides (H2O2) do what to alkenes?
convert them to 1,2-diols (glycols)
81
periodic acid (HIO4) added to a 1,2-diol (glycol) produces what?
ketones and aldehydes
82
how would one break an to alkene double bond into two carbonyl groups?
1) osmium tetroxide (OsO4) and peroxides (H2O2) to form the 1,2-diol (glycol)
2) periodic acid (HIO4) to produce ketones/aldehydes
83
converting an alcohol and an acid into an ester and water is called what?
a *dehydration condensation* called the **Fischer esterification** that takes place with an acid catalyst such as sulfuric acid (H2SO4)
84
what is the main consideration when setting up a generic Fischer esterification to convert alcohols and acids to esters?
**Le Chatelier's principle**, because the Fischer esterification is an equilibrium (often with an unfavorable equilibrium constant), clever techniques are often required to achieve good yields of esters. For example, we can use a large excess of the alcohol or the acid. Adding a dehydrating agent removes water (one of the products), driving the reaction to the right.
Acid chlorides (not yet covered) are more efficient than Fischer esterification.
85
how does the tosylate group (Ts) relate to esters?
In addition to forming esters with carboxylic acids, alcohols form inorganic esters with inorganic acids such as nitric acid, sulfuric acid, and phosphoric acid. In each type of ester, the alkoxy (-OR) group of the alcohol replaces a hydroxyl group of the acid, with loss of water. We have already studied tosylate esters, composed of *para*-toluenesulfonic acid and alcohols (but made using tosyl chloride). Tosylate esters are analogous to sulfate esters, which are composed of sulfuric acid and alcohols.
86
This reaction generates a sodium or potassium salt of an alkoxide ion and hydrogen gas.
## Footnote
The reactivity of alcohols toward sodium and potassium decreases in the order: methyl \> 1° \> 2° \> 3°. Sodium reacts quickly with primary alcohols and some secondary alcohols. Potassium is more reactive than sodium and is commonly used with tertiary alcohols and some secondary alcohols.
Some alcohols react sluggishly with both sodium and potassium. In these cases, a useful alternative is sodium hydride, usually in tetrahydrofuran solution. Sodium hydride reacts quickly to form the alkoxide, even with difficult compounds.
87
explain how you would convert an alcohol to an alkoxide?
This reaction generates a sodium or potassium salt of an alkoxide ion and hydrogen gas.
The reactivity of alcohols toward sodium and potassium decreases in the order: methyl \> 1° \> 2° \> 3°. Sodium reacts quickly with primary alcohols and some secondary alcohols. Potassium is more reactive than sodium and is commonly used with tertiary alcohols and some secondary alcohols.
Some alcohols react sluggishly with both sodium and potassium. In these cases, a useful alternative is sodium hydride, usually in tetrahydrofuran solution. Sodium hydride reacts quickly to form the alkoxide, even with difficult compounds.
88
describe the **Williamson ether synthesis**
Step 1: Form the alkoxide of the alcohol having the more hindered group.
Step 2: The alkoxide displaces the leaving group of a good SN2 substrate (such as a primary halide or tosylate).
89
what is important when comsidering the reactants in the **Williamson ether synthesis**?
The Williamson ether synthesis, is an SN2 displacement. The alkyl halide (or tosylate) must be primary so that a back-side attack is not hin- dered. When the alkyl halide is not primary, elimination usually results. ***The alkoxide must be formed from the alcohol having the more hindered group.***
