Ch. 7 Flashcards
1
Q
What makes a good leaving group and why?
( Does this vary for SN1 vs SN2)
A
Weak Bases are the Best Leaving Groups
In order for a leaving group to leave, it must be able to accept electrons. A strong bases wants to donate electrons; therefore, the leaving group must be a weak base.
As Electronegativity Increases, The Ability of the Leaving Group to Leave Increases.
As Size Increases, The Ability of the Leaving Group to Leave Increases
resonance increases the ability of the LG to leave
1
Q
How does electronegativity affect a leaving group?
A
As Electronegativity Increases, The Ability of the Leaving Group to Leave Increases. This is because an increase in electronegativity results in a species that wants to hold onto its electrons rather than donate them.
2
Q
what are alkyl halides?
A
compounds in which a halogen (such as Cl, Br, or I) is connected to an sp3 hybridized carbon atom
3
Q
what are Aryl halides and vinyl halides
A
a halogen is connected to an sp2 hybridized carbon atom
4
Q
what are the two general types of reactions for alkyl halids?
A
substitution and elimiantion
5
Q
substitution reaction
A
in which the nucleophile replaces the halogen
Reactions in which one group is replaced by another group.
6
Q
elimination reaction
A
A reaction involving the loss of a leaving group and formation of a π bond.
7
Q
substrate aka
A
alkyl halide
8
Q
isn the carbon connected to the halogen electrophilic nor nucleophilic and why?
A
The halogen withdraws electron density via induction, rendering the adjacent carbon atom electrophilic, and therefore subject to attack by a nucleophile.
9
Q
what makes a good leaving group in regards to acids
A
Good leaving groups are the conjugate bases of strong acids. For example, iodide (I−) is the conjugate base of a very strong acid (HI),
ie idodide is a very weak base
As a rule of thumb, a good leaving group is the conjugate base of an acid with a pKa < 0. For this reason, chloride, bromide, and iodide are all good leaving groups, while fluoride is not (the pKa of HF is 3.2)
10
Q
is hydroxide a good or bad leaving group?
A
hydroxide is a bad leaving group, because it is not a stabilized base. In fact, hydroxide is a relatively strong base, and therefore, it rarely functions as a leaving group
11
Q
among halides which is the best leaving group
A
iodide is the best leaving group bc it is the weakest base
12
Q
alpha position
A
the position immediately adjacent to the functional group
there is only one
13
Q
beta position
A
the position immediately adjacent to the alpha position
max of 3
14
Q
steps to name alkyl halides
A
- identify and name parent
- id and name the substituents
- number the parent chain and assign a locant to each substitute
- assemble subsituents alphabetically
15
Q
names for halogens
A
fluoro -
chloro-
bromo-
iodo-
16
Q
what does SN2 stand for?
A
bimolecular nucleophilic substitution
17
Q
Rate law for SN2 and explain why
A
Rate =K (alkyl halid) (nucleophile)
18
Q
rate law for SN1 and explain why
A
Rate = K( substrate)
rate is linearly dependent on the concentration of only one compound (the substrate)
19
Q
What is the mechanism for Sn2?
A
- Nucleophilic Attack
- loss of leaving group
a nucleophile attacks the alkyl halides, causing the loss of a leaving group in a CONCERTED
20
Q
what is the stereospecificity of SN2
A
inversion of configuration
During a reaction, when the configuration of a chiral center is changed.
21
Q
what is the requirement for inversion of configuration?
A
The requirement for inversion of configuration means that the nucleophile can only attack from the back side (the side opposite the leaving group) and never from the front side
6 making it stereospecific : a reaction in which the configuration of the product is dependent on the configuration of the starting material
22
Q
back-side attack
A
In SN2 reactions, the side opposite the leaving group, which is where the nucleophile attacks.
23
Q
why does a backside attack occur?
A
- The lone pairs of the leaving group create regions of high electron density that effectively block the front side of the substrate, so the nucleophile can only approach from the back side.
- Molecular orbital theory
homo and lumo
If a nucleophile attacks methyl bromide from the front side, the nucleophile will encounter a node, and as a result, no net bonding will result from the overlap between the HOMO of the nucleophile and the LUMO of the electrophile
24
How does the substrate effect the rate of an SN2 process?
fast - slow
primary > secondary> tertiary
25
Nucleophilicity
A term referring to the strength of a nucleophile, measured by the rate at which the nucleophile will attack a suitable electrophile.
26
How does NU strength affect SN2
A strong nucleophile will give a relatively fast SN2 reaction, while a weak nucleophile will give a relatively slow SN2 reaction. For this reason, a strong nucleophile is generally required in order for an SN2 reaction to be efficient and practical.
27
What factors affect Nu strength
explain each
charge and polarizability
negative charge = stronger
Recall that polarizability describes the ability of an atom to distribute its electron density unevenly as a result of external influences . Polarizability is directly related to the size of the atom and, more specifically, to the number of electrons that are distant from the nucleus. A sulfur atom is very large and has many electrons that are distant from the nucleus, and it is therefore highly polarizable. As a result, hydrosulfide (HS−) and thiolate (RS−) ions are particularly strong nucleophiles. Many of the halogens (especially iodide) share this same feature.
28
Is water a strong or weak NU ?
weak - lacks a charge
29
Is Fluorine a strong or weak Nu?
Fluoride can behave either as a weak nucleophile or as a strong nucleophile, depending on the identity of the solvent.
| in a protic solvents fluorine is the best Nu
in polar protic solvents fl
30
what affects the stability of a base ?
ARIO
31
what is the relationship between base and conjugate acid?
Inverse
strong base = weak conjugate acid
ex. I- = weak base and its conjugate acid HI is very strong
32
E2 reactions require what type of base?
STRONG bases
= beta elimination or 1,2 elimination in which the proton is removed from the beta postion and the halide is ejected as a leaving group from the alpha position
result = double bond
33
Beta elimination reaction ( E1/2 ) process is also called what?
dehydrohalogenation
bc H and X are removed from the substrate
34
E2 rate law
Rate = k ( alkyl halide)(base)
Based on these observations, we conclude that the mechanism must exhibit a step in which the alkyl halide and the base COLLIDE with each other. Because that step involves two chemical entities, it is said to be bimolecular.
35
What does E2 stand for ?
Bimolecular Elimination
36
describe the concerted mechanism of E2
a base removes a proton from the beta position of the alkyl halide, causing the loss of a leaving group and the formation of a C=C bond in a simultaneous method
Loss of a leaving group and proton transfer occur simultaneously
37
describe the effect of the substrate structure on the Rate of an E2
likes primary, secondary and tertiary
| ?????MORE?
38
when to use cis or trans vs E/Z?
You can always use the E/Z system. It is more reliable and particularly suited to tri- or tetra -substituted alkenes, especially when the substituents are not alkyl groups. The cis/trans system is not effective when there are more than two different substituents on a double bond.
39
what is more stable cis or trans and why
trans is always more stable
cis has more steric strain making it more unstable [
40
why are terta-substituted alkenes more stable than tri-substituted?
hyperconjugation, is a stabilizing effect because it enables the delocalization of electron density.
so tetra >tri> di> mono
41
Regiochemistry
A term describing a consideration that must be taken into account for a reaction in which two or more constitutional isomers can be formed.
42
when to consider regiochemistry?
In this example, the β positions are not identical, so the double bond can form in two different regions of the molecule. This consideration is an example of regiochemistry, and the reaction is said to produce two different regiochemical outcomes. Both products are formed, but the more substituted alkene is generally observed to be the major product.
43
regioselective
A reaction that can produce two or more constitutional isomers but nevertheless produces one as the major product.
44
Zaitsev Product
the more subsituted alkene and more stable
45
Hofmann product
less substituted and less stable
46
what determines major and minor product for Elimination reactions
major and minor are determined by base
BULKY favors Hoff
Small favors Zaitsev
47
bulky/ large bases
tBuoK ( always E2)
LDA
bulky produce hoffman bc they need the more sterically available hydrogen
48
common small bases
NaOme
NaOet
NaH
( remember Na is a counterion and spectator ion)
49
when to look at stereoselectivity
if the deprotonation of the Beta positions produces the same result ( both have the same amount of substitutes) look at cis vs trans
trans is more stable
50
What is important about C-C single bonds
they are free to rotate before the reaction occurs which allows them to achieve anti-coplanar and syn-coplanar
A conformation in which a hydrogen atom and a leaving group are separated by a dihedral angle of exactly 0°
51
anti-coplanar
A conformation in which a hydrogen atom and a leaving group are separated by a dihedral angle of exactly 180°
( staggared aka more stable)
elimintion reactions occur more rapidly
52
syn-coplanar
A conformation in which a hydrogen atom and a leaving group are separated by a dihedral angle of exactly 0°
( eclipsed so less stable)
53
periplanar
A conformation in which a hydrogen atom and a leaving group are approximately coplanar.
54
antiperiplanar
A conformation in which a hydrogen atom and a leaving group are separated by a dihedral angle of approximately 180°
the stereoisomeric product of an E2 process depends on the configuration of the starting alkyl halide:
55
E2 is stereospecific meaning...?
The stereospecificity of an E2 reaction is only relevant when the β position has only one proton
In such a case, the β proton must be arranged anti-periplanar to the leaving group in order for the reaction to occur, and that requirement will determine the stereoisomeric product obtained
If, however, the β position has two protons, then either of these two protons can be arranged so that it is anti-periplanar to the leaving group. As a result, both stereoisomeric products will be obtained
56
in a stereoselective E2 reaction:
The substrate itself is not necessarily stereoisomeric; nevertheless, this substrate can produce two stereoisomeric products, and it is found that one stereoisomeric product is formed in higher yield.
57
In a stereospecific E2 reaction
The substrate is stereoisomeric, and the stereochemical outcome is dependent on which stereoisomeric substrate is used.
58
stereospecificity of E2 Reactions on Substituted Cyclohexanes
In the other chair conformation, the leaving group occupies an equatorial position. The requirement for an anti-periplanar conformation demands that an E2 reaction can only occur from the chair conformation in which the leaving group occupies an axial position.
when the leaving group occupies an axial position, it is anti-periplanar
59
what solvent does Sn1 favor and why
Polar protic has a super strong partial positive and negative. it stabilizes both cations and anions
which slows down the SN2 reaction bc they are weaker NU
60
what solvent does Sn2 favor and why
partial positive is sterically blocked off from stabilizing the anions which keeps the NU strong
61
what does SN1 stand for
unimolecular nucleophilic substitution
62
what is the SN1 mechanism
1. loss of leaving group
2. carbocation intermediate
3. nucleophilic attack
63
E1 mechanism
When a tertiary alkyl halide undergoes ionization in a polar solvent, such as EtOH, the solvent can function as a base (rather than as a nucleophile) and deprotonate the intermediate carbocation, resulting in a two-step elimination process:
loss of leaving group - intermediate carbocation - proton transfer ( a base removed a beta proton to afford the product)
64
when an alkene is tri- or tetrasubstituted is the product E1 or Sn1 favored
elimination is generally favored over substitution when the resulting alkene is tri- or tetrasubstituted
65
when is rearrangement possible and how does it work
Sn1 only
Rearrangements occur to create more stable carbocations.
There are two types of rearrangements: hydride shift and alkyl shift.
hydride shift = rearrangements primarily occur between adjacent carbon atoms
alkyl shift = we see an alkyl group that shifts with the nucleophile
methyl shift
66
How does Substrate for E1 affect ionization rates ?
weak bases are better
SN1 and E1 processes are observed for tertiary alkyl halides and are rarely observed for secondary or primary alkyl halides, although there are exceptions. For example, the benzylic and allylic carbocations shown below are not tertiary, but they are stabilized by resonance, so they can serve as intermediates in unimolecular processes:
67
what is the stereochemisty for SN1?
scrambled + racemic mixture ( note the number of chiral centers - if there is only 1 chiral center it will always be racemic and both enantiomers are formed, but note of there r mulitple(?))
68
how to determine if SN or E reactions occurs or both
1. Determine the function of the reagent
( A substitution reaction occurs when the reagent functions as a nucleophile, while an elimination reaction occurs when the reagent functions as a base)
Nucleophilicity is determined by factors such as polarizability and the presence of high electron density, while basicity is determined by the stability of a base
2. Analyze the substrate and determine the expected mechanism(s)
3. consider any relevant regiochemical and stereochemical requirements
69
What are the products of a weak base and weak NU ?
primary = no reaction
secondary = E1/sN1
tertiary = E1/sN1 (polar protic..?)
70
What are the products of a
weak base and Strong NU ?
primary = Sn2
secondary = SN2
tertiary = sN1 (no rxn?)
71
What are the products of a
Strong base and Weak Nu ?
primary = E2
secondary = E2
tertiary = E2
72
What are the products of a
Strong base and Strong Nu ?
primary = Sn2 major E2 minor
secondary = E2 major Sn2 minor
tertiary = E2
73
common strong base and weak Nucleophiles
DBN and DBU
74
common strong base and strong Nu
HO-, MeO-, EtO-
75
Common Weak base and strong Nu
I-
Br-
Cl-
RS-
HS-
RSH
H2S
76
common weak base and weak Nu
H20
MeOH
EtOH
77
what is the regiochemical outcome for SN2 ?
The nucleophile attacks the alpha position where the leaving group is connected
78
what is the regiochemical outcome for SN1 ?
The nucleophile attacks the carbocation, which is generally where the leaving group was originally connected, unless a carbocation rearrangement took place.
79
what is the regiochemical outcome for E2 ?
The Zaitsev product is generally favored over the Hofmann product, unless a sterically hindered base is used, in which case the Hofmann product will be favored
80
what is the regiochemical outcome for E1 ?
The Zaitsev product is always favored over the Hofmann product.
81
what is the stereochemical outcome for Sn2
The nucleophile replaces the leaving group with inversion of configuration.
82
what is the stereochemical outcome for E2
This process is stereoselective, because when applicable, a trans disubstituted alkene will be favored over a cis disubstituted alkene. This process is also stereospecific. Specifically, when the β position of the substrate has only one proton, the stereoisomeric alkene resulting from anti-periplanar elimination will be obtained (exclusively, in most cases).
83
what is the stereochemical outcome for Sn1
The nucleophile replaces the leaving group to give a nearly racemic mixture. In practice, there is generally a slight preference for inversion over retention of configuration, as a result of the effect of ion pairs.
84
what is the stereochemical outcome for E1
The process is stereoselective. When applicable, a trans disubstituted alkene will be favored over a cis disubstituted alkene.
85
Tosylates
ROTs
86
mesylates
MsOH pka = -1.9
87
triflates
TfOh ( pka = -14)
best leaving group and weak base
88
kinetic isotope effect
Kinetic Isotope Effects (KIEs) are used to determine reaction mechanisms by determining rate limiting steps and transition states and are commonly measured using NMR to detect isotope location or GC/MS to detect mass changes.
89
naming alkenes
The four steps for naming are: Identify and name the parent chain. Identify and name the substituents. Number the parent chain to give the lowest locant to the double bond and assign a locant to each substituent. Assemble the substituents alphabetically.
ex.The parent is an octene since the longest chain is 8 carbons long and has a double bond. The substituents are 1 ethyl group on C3, 3 methyl groups on C4, C5, and C6, and a double bond on C3. This gives 3-ethyl-4,5,6-trimethyloct-3-ene.
90
is DMSO polar protic or polar A protic
A protic
91
which solvent favors Sn2
a protic
92
which solvent favors Sn1
protic
( shield)
93
are alcohols polar protic or polar A protic?
Protic
94
how does steric hinderance affect rate
more steric hinderance = slower
less steric hinderance = faster
95
What is a nucleophile and electrophile
a nucleophile is an atom that
96
Polar aprotic solvents enhance the rate of an SN2 reaction by
raising the energy of the nucleophile, giving a smaller Ea. They cannot stabilize the anions and do not affect the polarizibility of the nucleophiles.
