Substitution and Elimination Reactions Flashcards
(153 cards)
1
Q
What is the general rate law for SN2 reactions?
A
Rate = k[substrate][nucleophile], indicating a second-order, bimolecular mechanism.
2
Q
What is the order of relative rates for SN2 reactions with different alkyl halides?
A
Methyl > Primary > Secondary > Tertiary, with methyl being the fastest and tertiary not undergoing SN2.
3
Q
What is the general rate law for SN1 reactions?
A
Rate = k[substrate], indicating a first-order reaction.
4
Q
What is the typical effect of polar protic solvents on SN2 reaction rates?
A
They decrease nucleophilicity and slow SN2 reactions by stabilizing the nucleophile through hydrogen bonding.
5
Q
Which reaction pathway is favored when the nucleophile is weak and the substrate is tertiary?
A
SN1 or E1 mechanisms are favored due to carbocation stability.
6
Q
In SN2 reactions, what does the term ‘concerted’ imply?
A
The reaction occurs in a single step without intermediates, with simultaneous bond breaking and forming.
7
Q
What stereochemical requirement is generally necessary for E2 elimination to occur?
A
The proton and leaving group must be in an anti-periplanar (antiperiplanar) arrangement.
8
Q
Why are tertiary carbocations more reactive in SN1 reactions?
A
Tertiary carbocations are more stabilized due to hyperconjugation and inductive effects, making them more reactive in SN1 reactions.
9
Q
What factors favor SN1 over SN2 mechanisms?
A
Tertiary substrates, weak nucleophiles, polar protic solvents, and higher temperatures favor SN1 mechanisms.
10
Q
Which type of carbocation stability favors SN1 reactions?
A
Tertiary carbocations are more stabilized and thus favor SN1 reactions.
11
Q
What is the effect of nucleophile strength on SN2 and SN1 reactions?
A
Strong nucleophiles favor SN2 reactions, while weak nucleophiles favor SN1, as the rate of SN1 depends mainly on substrate stability.
12
Q
What is the impact of nucleophile concentration on SN2 and SN1 reactions?
A
SN2 rate increases with nucleophile concentration, while SN1 rate is independent of nucleophile concentration.
13
Q
In SN2 reactions, from which side does the nucleophile approach the substrate?
A
The nucleophile approaches from the backside of the leaving group, leading to inversion of stereochemistry.
14
Q
In E2 reactions, what is the significance of the anti-periplanar conformation?
A
The anti-periplanar conformation allows optimal overlap of orbitals for elimination, making the reaction more efficient.
15
Q
How does steric hindrance affect SN2 reaction rates?
A
Increased steric hindrance around the electrophilic carbon decreases SN2 reaction rate by obstructing nucleophile approach.
16
Q
What is the primary role of a nucleophile in nucleophilic substitution reactions?
A
A nucleophile attacks the carbon atom bearing the leaving group, donating an electron pair to form a new bond.
17
Q
Which halides are most reactive in SN1 reactions?
A
Tertiary halides are most reactive in SN1 reactions due to stable carbocation formation.
18
Q
What factors favor SN2 reactions over SN1?
A
SN2 reactions are favored by primary substrates, strong nucleophiles, polar aprotic solvents, and lower steric hindrance around the electrophilic carbon.
19
Q
How does solvent polarity affect SN2 reaction rates?
A
Polar aprotic solvents increase SN2 rates by not hydrogen-bonding to nucleophiles, thus maintaining their nucleophilicity, while polar protic solvents decrease it.
20
Q
Why are 4-membered rings less common in intramolecular substitution reactions?
A
4-membered rings are strained and the reacting ends are farther apart than in 3-membered rings, slowing the reaction.
21
Q
How does increasing substitution at the carbon attached to the leaving group affect SN2 reaction rate?
A
It hinders the approach of the nucleophile, increases activation energy, and decreases the SN2 reaction rate.
22
Q
What is the primary mechanism of the SN1 reaction?
A
SN1 reactions involve a carbocation intermediate formed by the loss of the leaving group, followed by nucleophilic attack from either face of the planar carbocation, leading to racemization.
23
Q
How do polar aprotic solvents influence nucleophilicity and SN2 reactions?
A
They do not hydrogen-bond with nucleophiles, enhancing nucleophilicity and increasing SN2 reaction rates.
24
Q
Describe the stereochemical outcome of an SN2 reaction involving a stereocenter.
A
SN2 reactions produce an inverted stereoisomer relative to the starting halide due to backside attack.
25
What is Zaitsev's Rule in elimination reactions?
Zaitsev's Rule states that the more substituted (more stable) alkene is the predominant product in elimination reactions.
26
What is the defining characteristic of SN1 reactions regarding their dependence on reactant concentration?
SN1 reaction rate depends only on the concentration of the substrate, indicating a first-order mechanism.
27
What is the stereochemical outcome of SN1 reactions involving chiral substrates?
SN1 reactions produce a racemic mixture due to the planar carbocation intermediate, allowing attack from either face.
28
What is the significance of the transition state in a nucleophilic substitution mechanism?
The transition state represents the highest energy point along the reaction pathway where bonds are partially broken and formed.
29
What is Zaitsev's Rule in elimination reactions?
The more substituted and more stable alkene is typically the predominant product in E2 eliminations.
30
How does solvent polarity influence SN1 reactions?
Polar protic solvents stabilize the carbocation intermediate and the leaving group, thus increasing the rate of SN1 reactions.
31
How does the leaving group influence the rate of nucleophilic substitution?
Better leaving groups (like I– and Br–) increase the rate of both SN1 and SN2 reactions due to easier departure.
32
What is the main difference between SN1 and SN2 reaction mechanisms?
SN1 is a two-step process involving carbocation formation and racemization, while SN2 is a one-step, concerted reaction with backside attack and inversion of configuration.
33
What stereochemical arrangement is required for E2 elimination to occur efficiently?
The proton being abstracted and the leaving group must be in an anti-periplanar (antiperiplanar) conformation, often trans and diaxial in cyclohexanes.
34
What is intramolecular nucleophilic substitution, and what is its typical outcome?
Intramolecular nucleophilic substitution involves nucleophile and leaving group in the same molecule, often resulting in ring formation, especially favored for 3, 5, and 6 membered rings.
35
How does temperature influence elimination reactions like E2?
Higher temperatures generally favor elimination (E2) over substitution due to entropy considerations.
36
What is the role of the base in E2 elimination?
The base abstracts a proton from a β-carbon while the leaving group departs, all in a single concerted step.
37
What are the typical reaction pathways for a primary alkyl halide in nucleophilic substitution?
Primary alkyl halides typically undergo SN2 reactions due to minimal steric hindrance.
38
What is the main factor that determines whether SN1 or SN2 occurs?
The substrate structure, nucleophile strength, solvent, and temperature influence whether SN1 or SN2 occurs, with SN1 favored by tertiary substrates and polar protic solvents.
39
What is the typical order of reactivity for alkyl halides in SN2 reactions?
Methyl > primary > secondary > tertiary, with reactivity decreasing as substitution increases.
40
41
What is the default pathway for a Methyl or Primary Carbon substrate bearing a leaving group?
SN2 is typically observed
## Footnote
Steric hindrance is minimal, allowing the nucleophile to approach the backside for substitution.
42
Under what conditions does E2 become favored for Methyl or Primary Carbon substrates?
If a strong, highly hindered base is used at elevated temperatures
## Footnote
The bulk of the base and higher temperature favor elimination.
43
What happens when a tertiary carbon substrate has a strong base present?
E2 is heavily favored
## Footnote
Steric hindrance around the tertiary carbon makes SN2 impossible.
44
What is favored when a tertiary carbon substrate has a weak nucleophile/base present?
SN1 and E1 are favored
## Footnote
The tertiary carbon can form a stable carbocation intermediate.
45
What conditions favor SN2 for a Secondary Carbon substrate?
If the attacking species is a weak/moderate nucleophile and less basic than HO⁻
## Footnote
Examples include CN⁻, N₃⁻, SR⁻.
46
What conditions favor E2 for a Secondary Carbon substrate?
If the attacking species is a strong base and beta hydrogens are present
## Footnote
Strong bases include HO⁻, RO⁻, R₂N⁻, RCC⁻.
47
What is the reactivity of Allylic or Benzylic substrates in unimolecular reactions?
These substrates can form resonance-stabilized carbocations, making them highly reactive
## Footnote
Applicable for 1°, 2°, or 3° allylic/benzylic halides.
48
What occurs if a strong nucleophile is present for Allylic or Benzylic halides?
SN2 can occur, especially for 1° and 2° halides
## Footnote
Provided steric hindrance isn't excessive.
49
What reactions are favored for tertiary allylic and benzylic halides with a weak nucleophile/base?
SN1 and E1 are highly favored
## Footnote
Due to the stability of the resonance-stabilized carbocation.
50
What do strong nucleophiles / strong bases favor?
Bimolecular reactions (SN2 and E2)
## Footnote
They are directly involved in the rate-determining step.
51
What do weak nucleophiles / weak bases favor?
Unimolecular reactions (SN1 and E1)
## Footnote
They are not involved in the rate-determining step.
52
What type of reactions do bulky bases strongly promote?
E2 reactions
## Footnote
Often leading to the less substituted (Hofmann) product.
53
What do polar protic solvents favor?
SN1 and E1 reactions
## Footnote
They stabilize the carbocation intermediate and the leaving group.
54
What do polar aprotic solvents favor?
SN2 reactions
## Footnote
They do not effectively solvate anions, leaving the nucleophile more reactive.
55
How do higher temperatures affect reaction pathways?
They generally favor elimination reactions (E1 and E2) over substitution reactions
## Footnote
Due to a more positive change in entropy.
56
What is essential for all four mechanisms regarding the leaving group?
A good leaving group is essential (a weak base, e.g., I⁻ > Br⁻ > Cl⁻ > F⁻)
## Footnote
A better leaving group increases the rate of reaction.
57
What are examples of Very Good Nucleophiles?
I⁻ (Iodide ion)
RS⁻ (Thiolate ions, e.g., CH₃S⁻)
## Footnote
Very Good Nucleophiles are highly reactive and readily donate electrons.
58
What are examples of Good Nucleophiles?
Br⁻ (Bromide ion)
HO⁻ (Hydroxide ion)
RO⁻ (Alkoxide ions, e.g., CH₃O⁻)
N₃⁻ (Azide ion)
⁻CN (Cyanide ion)
RNH⁻ (Amide ions, e.g., CH₃NH⁻)
## Footnote
Good Nucleophiles have a moderate ability to donate electrons.
59
What are examples of Fair Nucleophiles?
Cl⁻ (Chloride ion)
F⁻ (Fluoride ion)
RCO₂⁻ (Carboxylate ions, e.g., CH₃CO₂⁻)
RSH (Thiols, neutral)
RNH₂ (Amines, neutral, e.g., CH₃NH₂)
NH₃ (Ammonia)
## Footnote
Fair Nucleophiles are less reactive than Good Nucleophiles.
60
What are examples of Poor (Weak) Nucleophiles?
ROH (Alcohols, neutral, e.g., CH₃OH)
HOH (Water, neutral)
RCO₂H (Carboxylic acids, neutral, e.g., CH₃CO₂H)
## Footnote
Poor Nucleophiles have a low tendency to donate electrons.
61
What is a common feature of Group II compounds?
All have electron-withdrawing groups bonded to sp³ carbons
62
What types of reactions do Group II compounds typically undergo?
Substitution and/or elimination reactions
63
What is the reactivity principle for Group II compounds?
The weaker the base (leaving group), the more easily it is displaced
64
List the members of Group II compounds.
* Alkyl halides
* Alcohols
* Ethers
* Epoxides
* Quaternary ammonium hydroxides
* Sulfonate esters
* Sulfonium salts
65
What challenge does the OH⁻ group present as a leaving group in alcohols?
OH⁻ is a strong base and poor leaving group
66
What must occur for alcohols to undergo substitution or elimination?
They must be 'activated'
67
Which type of alcohols readily undergo SN1 reactions at room temperature?
Tertiary alcohols
68
What do secondary alcohols require to undergo SN1 reactions?
Heat
69
Can primary alcohols undergo SN1 reactions?
No, they cannot (unstable primary carbocations)
70
Which mechanism do primary alcohols follow for reactions?
SN2 mechanism
71
What is required for primary alcohols to react via the SN2 mechanism?
Protonation to create a better leaving group (H₂O)
72
What do alcohols form during dehydration?
Alkenes
73
What is the order of reactivity for dehydration of alcohols?
tertiary > secondary > primary
74
Which mechanism do secondary and tertiary alcohols follow for dehydration?
E1 mechanism
75
Which mechanism do primary alcohols follow for dehydration?
E2 mechanism
76
What rule does the major product of alcohol dehydration follow?
Zaitsev's rule (more substituted alkene)
77
What reaction occurs when alcohols react with hydrogen halides?
ROH + HX → RX + H₂O
78
What is the Lucas test used for?
To observe different rates of reaction of alcohols with HCl/ZnCl₂
79
What are the reaction rates in the Lucas test for tertiary, secondary, and primary alcohols?
* Tertiary: immediate
* Secondary: 1-5 min
* Primary: requires heat
80
What is the role of phosphorus halides in alcohol activation?
Gives high yields and avoids rearrangements
81
What does thionyl chloride (SOCl₂) do to alcohol?
Converts OH to Cl
82
What do sulfonate esters create as a result of using TsCl (tosyl chloride)?
Excellent leaving group
83
How do ethers compare to alcohols in terms of leaving groups?
Like alcohols, ethers have poor leaving groups
84
What is required for ethers to undergo reactions?
Protonation with strong acids (HI, HBr)
85
In SN2 reactions involving ethers, where does the nucleophile attack?
Less sterically hindered carbon
86
Why are epoxides more reactive than ethers?
Due to ring strain
87
Under acidic conditions, which carbon does the nucleophile attack in epoxides?
More substituted carbon
88
Under basic/neutral conditions, which carbon does the nucleophile attack in epoxides?
Less hindered carbon
89
What do quaternary ammonium hydroxides undergo in elimination reactions?
Hofmann elimination (E2 mechanism)
90
What type of alkene do quaternary ammonium hydroxides produce?
Less substituted alkene (anti-Zaitsev)
91
What conditions are required for Hofmann elimination?
Requires heat
92
Why are sulfonate esters and sulfonium salts excellent leaving groups?
Due to charge delocalization
93
At what temperature do sulfonate esters readily undergo SN2 reactions?
Room temperature
94
What is the exception for tertiary sulfonate esters?
They undergo elimination instead of substitution
95
What is S-adenosylmethionine (SAM) known as?
Biological methylating agent (sulfonium ion)
96
What are arene oxides known for in biological contexts?
Can be carcinogenic by reacting with DNA
97
How do thiols compare to alcohols in terms of acidity and nucleophilicity?
Thiols are stronger acids and better nucleophiles in protic solvents
98
What is retained when alcohol is converted to alkyl halide via PBr₃/PCl₃?
Configuration
99
What happens to configuration when alcohol is converted to alkyl halide via sulfonate ester?
Inverts configuration
100
What is the typical product in dehydration of alcohols?
Trans isomer usually predominates (more stable)
101
What occurs in epoxidation followed by nucleophile attack?
Trans addition
102
What does osmium tetroxide do to alkenes?
Forms cis diols
103
What is the first step in the SN1 mechanism for tertiary alcohols?
Protonation: The acid (HX) protonates the oxygen of the alcohol
104
What happens during heterolytic cleavage in the SN1 mechanism?
The protonated alcohol loses water to form a carbocation
105
What is the final step in the SN1 mechanism for tertiary alcohols?
Nucleophile (X-) attacks the carbocation
106
What is a hydride shift in carbocation rearrangement?
A hydrogen with its electron pair moves from an adjacent carbon
107
What is an alkyl shift in carbocation rearrangement?
An alkyl group with its electron pair moves
108
What is the first step in the SN2 mechanism for primary alcohols?
Protonation: The acid protonates the oxygen of the alcohol
109
What occurs during the nucleophilic attack in the SN2 mechanism?
The nucleophile attacks from the backside while water leaves
110
What does ZnCl2 do in the SN2 mechanism for alcohols?
Complexes with the alcohol oxygen
111
What is the role of PBr3 in alcohol activation?
Alcohol oxygen attacks phosphorus
112
What happens during substitution in PBr3 activation?
Bromide ion attacks carbon with departure of the good leaving group
113
What is the mechanism for SOCl2 activation?
Alcohol oxygen attacks sulfur of SOCl2
114
What does pyridine do in tosylate formation?
Removes the proton from alcohol
115
What is the result of nucleophilic attack on sulfonyl group of TsCl?
Formation of tosylate (RO-Ts)
116
What is the first step in the E1 mechanism for secondary/tertiary alcohols?
Protonation: H2SO4 protonates the alcohol oxygen
117
What occurs after carbocation formation in the E1 mechanism?
Loss of β-hydrogen forms alkene
118
What happens in the E2 mechanism for primary alcohols?
Base removes β-hydrogen while water leaves
119
What is the first step in ether reactions with HI?
Protonation: HI protonates the ether oxygen
120
thiols, sulfides, sulfonium ions
thiols --> better nucleophiles in polar protic solvents
sulfides --> very good nucleophile
sulfonium ions --> really good leaving group
121
In the base-catalyzed mechanism for epoxides, where does the nucleophile attack?
Less hindered carbon
122
What is the mechanism of Hofmann elimination?
Base attack removes a β-hydrogen, breaking the C-N bond
123
What type of addition occurs in nucleophilic addition to arene oxides?
anti addition
124
What is the result of the NIH shift during arene oxide reactions?
Formation of phenol
125
What is the stereochemistry outcome when alcohol is converted to alkyl halide via PBr3/PCl₃?
Net retention of configuration
126
What is the stereochemical result of sulfonate ester reactions?
Inversion of configuration
127
What do E1 mechanisms typically produce in cyclic systems?
More stable trans isomer
128
In epoxide ring-opening, where does the nucleophile attack?
From the side opposite the epoxide ring
129
What does osmium tetroxide addition preserve in cis diol formation?
Cis geometry
130
131
What are the oxidation products of primary alcohols?
Aldehydes or carboxylic acids
## Footnote
Primary alcohols can be oxidized to aldehydes or further to carboxylic acids.
132
What are secondary alcohols oxidized to?
Ketones
## Footnote
Secondary alcohols are oxidized to ketones.
133
Why can't tertiary alcohols be oxidized by conventional methods?
They lack a hydrogen atom on the carbon bonded to the hydroxyl group
## Footnote
Tertiary alcohols generally cannot be oxidized by these methods.
134
What is chromic acid?
H2CrO4
## Footnote
Chromic acid is formed from chromium trioxide (CrO3) or dichromate salts in aqueous acid.
135
What does pyridinium chlorochromate (PCC) do?
Stops oxidation of primary alcohols at the aldehyde stage
## Footnote
PCC is a milder chromium-based reagent used for selective oxidation.
136
What is required for PCC to prevent further oxidation?
An anhydrous solvent
## Footnote
An example of an anhydrous solvent is dichloromethane.
137
What is a less toxic alternative for alcohol oxidation?
Hypochlorous acid (HOCl)
## Footnote
Hypochlorous acid is generated in situ within the reaction mixture.
138
What are the oxidation products of primary alcohols using hypochlorous acid?
Aldehydes
## Footnote
Primary alcohols are oxidized to aldehydes by hypochlorous acid.
139
What is the mechanism of oxidation by hypochlorous acid?
Protonation, oxidation by hypochlorite ion, deprotonation
## Footnote
This results in the formation of the carbonyl product.
140
What is the Swern oxidation known for?
Mild conditions at low temperatures
## Footnote
Typically occurs at temperatures around -60 °C.
141
What reagents are used in the Swern oxidation?
Oxalyl chloride, dimethyl sulfoxide, triethylamine
## Footnote
The combination of these reagents allows for effective oxidation.
142
What products are formed from secondary alcohols in Swern oxidation?
Ketones
## Footnote
Secondary alcohols are oxidized to ketones in this method.
143
What intermediate is formed during Swern oxidation?
Dimethyldichlorosulfonium ion
## Footnote
This intermediate is crucial for the oxidation process.
144
What role does triethylamine play in the Swern oxidation?
Acts as a base to remove a proton
## Footnote
This occurs in an E2 reaction to form the desired product.
145
grignard reagents
organometallic reagents
146
formaldehyde grignard
primary alcohol
147
grignard aldehyde
2 alc
148
ketone grignard
3 alc
149
ester
3 alc(w/addition of two molecules of grignard reagent)
150
ethylene oxide grignard
primary alcohol
151
formation of grignard reagent
R-X + Mg --(diethyl ether)--> R(partial negative)-Mg-X ---(H2O) ---> R-H
152
williamson ether synthesis
SN2 reaction of alkoxide with alkyl halide
best results obtained when alkyl halide is methyl or primary (secondary or tertiary undrgo
153
alcohol + sulfonyl chloride
sulfonate ester
