Organic Chemistry (I)

Alkyl Halides
o Alkyl halides are organic molecules containing a halogen atom bonded to
an sp3 hybridized carbon atom.

o Alkyl halides are classified as primary (1°), secondary (2°), or tertiary

Chapter 7. (3°), depending on the number of carbons bonded to the carbon with the
halogen atom.
Alkyl Halides &
o The halogen atom in halides is often denoted by the symbol “X”.
Nucleophilic
Substitution

7.1 Introduction to Alkyl Halides 2

Types of Alkyl Halides Naming Alkyl Halides: IUPAC

o Other types of organic halides include vinyl halides, aryl halides, allylic
halides, and benzylic halides. 보기
Sub Stuart로
o Vinyl halides have a halogen atom (X) bonded to a C-C double bond. or
o Aryl halides have a halogen atom bonded to a benzene ring.

o Allylic halides have X bonded to the carbon atom adjacent to a C-C

double bond. 4페닐
o Benzylic halides have X bonded to the carbon atom adjacent to a benzene
ring.
모양 정도 기억해두기
g

& c
'
c
N

7.1 Introduction to Alkyl Halides 3 7.2 Nomenclature 4

 Naming Alkyl Halides: Common Names Naming Alkyl Halides

o Common names are often used for simple alkyl halides. To assign a
common name: Prob. 7.4. Give the IUPAC name

- Name all the carbon atoms of the molecule as a single alkyl group.

Eleanor
Br
CH3
- Name the halogen bonded to the alkyl group.
H3C CH3

- Combine the names of the alkyl group and halide, separating the words H3C CH3 Br

with a space.
2-Bromo-5.int
imethylheptanetbwmo-2-mettylcydohe.ae
F

CH3
H3C
CH3

CH3

7.2 Nomenclature 5 7.2 Nomenclature 6

Physical Properties Physical Properties

o Alkyl halides are weakly polar molecules.

o They exhibit dipole-dipole interactions because of their polar C-X bond.

o Since the rest of the molecule contains only C-C and C-H bonds, they are - 액체로 로제
.

incapable of intermolecular hydrogen bonding.

mp.b.pt 높다는 걸 예측가능 .

대
polamab.tt
( 분극형성이 더 잘 됨?

7.3 Physical Properties 7 7.3 Physical Properties 8

 Simple Alkyl Halides Simple Alkyl Halides

7.4 Interesting Alkyl Halides 9 7.4 Interesting Alkyl Halides 10

Polar Carbon-Halogen Bond Nucleophilic Substitution Reactions

o The electronegative halogen atom in alkyl halides creates a polar C-X o Three components are necessary in any substitution reaction.

bond, making the carbon atom electron deficient. - R – Alkyl group containing sp3 hybridized carbon bonded to X
- X – leaving group i.e., halide anions, H2O (ROH2+), N2 (RN2+), etc
o This electron deficient carbon is a key site in the reactivity of alkyl
- :Nu– - nucleophile containing lone pair or π bond
halides.
o Necleophilic substitutions are Lewis acid-base reactions

ffhty.tl
r Lewis
base 이긴함

C에 전자를 줌
Ch 7
↑
얘가떨어지고
T2mAU
안정성 비교
( 짝산의 Ka 비교 >
p

↳ H에 전자를 Ch 8
좀

11
“Salt” is often omitted 12
7.5 The Polar Carbon-Halogen Bond 7.6 General Features of Nucleophilic Substitution
 Nucleophilic Substitution Reactions Nucleophilic Substitution Reactions
o When a neutral nucleophile is used, the substitution product bears a o The overall effect of any nucleophilic substitution is the replacement of
positive charge. the leaving group by the nucleophile.
C와 bond Ty

9 o To draw any nucleophilic substitution product:

g.

→
-
N H -

, .in
- Find the sp3 hybridized carbon with the leaving group.

depwtonizeq-Y.og_ne.cl
- Identify the nucleophile, the species with a lone pair or π bond.
o The substitution product’s positive charge is usually caused by a proton - Substitute the nucleophile for the leaving group and assign charges (if
bonded to O or N. necessary) to any atom that is involved in bond breaking or bond
o That proton is readily lost from this in a Brønsted-Lowry acid-base formation.
reaction, forming a neutral product.

Prob 7.9
이사
CH3

+ :N(CH2CH3)3
H3C ○
Br

v8

lwavirggwrp.ly
7.6 General Features of Nucleophilic Substitution 13 7.6 General Features of Nucleophilic Substitution 14

Leaving Group: What makes a good leaving group? Leaving Group: What makes a good leaving group?
o In a nucleophilic substitution reaction of R–X, the C–X bond is o The weaker the base, the better the leaving group.
heterolytically cleaved, and the leaving group departs with the electron
pair in that bond, forming X:¯. ↑

o The more stable the leaving group X:¯, the better able it is to accept an
electron pair.

o For example, H2O is a better leaving group than HO¯ because H2O is a
weaker base.

'
H싷a쬯[ 작음 → 짝염기 안정

큼 → 짝염기 불안정
HF와 牡中 HI가 강산

7.7 The Leaving Group 15 7.7 The Leaving Group 16

 Leaving Group: What makes a good leaving group? Leaving Group: What makes a good leaving group?
o All good leaving groups are weak bases with strong conjugate acids having o Conjugate bases of weaker acids are poorer leaving groups.
low pKa values.

안정성

:
:
- .
t
얘들의

↳ 그렇게 도은 teau Tag

group은 아님

7.7 The Leaving Group 17 7.7 The Leaving Group 18

Leaving Group: What makes a good leaving group? Nucleophile

o Equilibrium favors the products of nucleophilic substitution when the o Nucleophiles and bases are structurally similar: both have a lone pair or a
leaving group is a weaker base than the nucleophile. π bond.
E가 더 낮은
→ 반응물 생성물 中 o They differ in what they attack.

- Bases attack protons.

o o
v - Nucleophiles attack other electron-deficient atoms (usually carbons).
-

얘네들의 안정성이 더 영향을 크게 준다 .

19 20
7.7 The Leaving Group
정반쁘% 7.8 The Nucleophile
 Nucleophilicity vs. Basicity Nucleophilicity vs. Basicity
o Nucleophilicity parallels basicity in three instances.
o Generally it is true that strong base is a strong nucleophile.
1. For two nucleophiles with the same nucleophilic atom, the stronger base

o Although nucleophilicity and basicity are interrelated, they are is the stronger nucleophile.

fundamentally different. - The relative nucleophilicity of HO¯ and CH3COO¯, is determined by

Ka (평형을 기반) comparing the pKa values of their conjugate acids (H2O = 15.7, and
g. p
o Basicity is a measure of how readily an atom donates its electron pair to
CH3COOH = 4.8).
a proton. It is characterized by an equilibrium constant, Ka in an acid-
- HO¯ is a stronger base and stronger nucleophile than CH3COO¯.
base reaction, making it a thermodynamic property. -

↳ 열역학적 평형기반 2. A negatively charged nucleophile is always a stronger nucleophile than its
o Nucleophilicity is a measure of how readily an atom donates its electron conjugate acid.
pair to other atoms. It is characterized by a rate constant, k, making it a - HO¯ is a stronger base and stronger nucleophile than H2O.
이것도 고려해야 함
kinetic property. 두 tos .

3. Right-to-left across a row of the periodic table, nucleophilicity increases

↳ Carbon Attack 얼마나?
.
"
stt3
☐
as basicity increases:
(공간이 상대적으로 4) (공간이 상대적으로 적음 )

7.8 The Nucleophile 21 7.8 The Nucleophile 22

base-nude.pro
Nucleophilicity vs. Steric Effects 같은 coy.nl 일수 ◦ .

Nucleophilicity vs. Solvent Effects

o Nucleophilicity does not parallel basicity when steric hindrance becomes
important. o Most organic reactions are performed in a liquid solvent capable of
평형상수값은
dissolving the reactants, at least to some extent.
o Steric hindrance is a decrease in reactivity resulting from the presence 도입불가 .

of bulky groups at the site of a reaction. o Since substitution reactions involve polar starting materials, polar
o Steric hindrance decreases nucleophilicity but not basicity. solvents are used to dissolve them.

o Sterically hindered bases that are poor nucleophiles are called msn.sc#yo.hhgmbatgx
o There are two type of polar solvents: protic and aprotic.
nonnucleophilic bases.
" o Nucleophilicity can be affected by the nature of the solvent.

→
용매 속에서 안정하게 존재할 수 있는 경우 0
Memphis 공격하지 않고도

7.8 The Nucleophile 23 7.8 The Nucleophile 24

 Nucleophilicity vs. Solvent Effects Nucleophilicity vs. Solvent Effects
o Polar protic solvents are capable of intermolecular hydrogen bonding, because
o In polar protic solvents, nucleophilicity increases down a column of the
they contain an O-H or N-H bond.
periodic table as the size of the anion increases. This is the opposite of
o Polar protic solvents solvate both cations and anions well. ! basicity.

Zone수고결합은
아닌가
- Cations are solvated by ion-dipole interaction. o Smaller, more electronegative anions are solvated more strongly, effectively
wo.it#.
- Anions are solvated by hydrogen bonding. shielding them from reaction.
o If the salt NaBr is used as a source of the nucleophile Br¯ in H2O: 안정한 앤데

ET
mdeyhik.ee
여기선 강란
- The Na+ cations are solvated by ion-dipole interactions with H2O molecules.
hs 공간이 더 많아서
- The Br¯ anions are solvated by strong hydrogen bonding interactions.
역전
좀 더 반응하기 쉬움
p沁땍
.

m.de

Examples of polar protic solvents

7.8 The Nucleophile 25 7.8 The Nucleophile 26

일반라 시키기에는 약간 무리 ?
Nucleophilicity vs. Solvent Effects Nucleophilicity vs. Solvent Effects
. .

o Polar aprotic solvents exhibit dipole-dipole interactions, but are incapable of o Anions are not well solvated in polar aprotic solvents, there is no need to
hydrogen bonding (i.e., no O-H or N-H bond). consider if solvent molecules more effectively hide one anion than other.

o Polar aprotic solvents solvate only cations well. o In polar aprotic solvents, nucleophilicity parallels basicity, and the stronger

- Cations are solvated by ion-dipole interaction. base is the stronger nucleophile.

- Anions are not well solvated because the solvent cannot hydrogen bond. o Because basicity decreases as size increases down a column, nucleophilicity
decreases as well. Radar ✗
o If the salt NaBr is dissolved in acetone:
or gap
- The Na+ cations are solvated by ion-dipole interactions with acetone.
- The Br¯ anions are not well solvated, and called naked anions.
☐
Examples of
polar aprotic solvents

7.8 The Nucleophile 27 7.8 The Nucleophile 28

 Nucleophilicity Nucleophilicity
o Central relationship between nucleophilicity and basicity:
Prob 7.16 Rank the nucleophilies in in order of increasing nucleophilicity.
1. It is generally true that the stronger base is the stronger nucleophiles
(a) –OH, –NH2, H2O
2. In polar protic solvents, however, nucleophilicity increases with increasing
size of an anion (opposite to basicity).
(b) –OH, Br–, F– (polar aprotic solvent)
3. Steric hindrance decreases nucleophilicity without decreasing basicity,
making (CH3)3CO– a stronger base but a weaker nucleophile than CH3CH2O–.
(c) H2O, –OH, CH3COO–

7.8 The Nucleophile 29 7.8 The Nucleophile 30

Mechanisms for Nucleophilic Substitution Mechanisms for Nucleophilic Substitution

Possibility 1.
-

o Nucleophilic substitution involves two σ bonds: -

o Bond making and bond breaking occur at the same time.

1. Bond to leaving group
o The mechanism is comprised of one step.
2. Bond to nucleophile
o In such a bimolecular reaction, the rate depends upon the
o To understand the mechanism of the reaction, we must know the timing of
concentration of both reactants.
these two events.
o The rate equation is second order.
o “What is the order of bond breaking and bond making?”

2차반응

State)
Na - - -
R .
. .

x (Transiton
7.9 Possible Mechanisms for Nucleophilic Substitution 31 7.9 Possible Mechanisms for Nucleophilic Substitution 32
 Mechanisms for Nucleophilic Substitution Mechanisms for Nucleophilic Substitution
Possibility 2. Possibility 3.

o Bond breaking occurs before bond making. o Bond making occurs before bond breaking.

o The mechanism has two steps and a carbocation is formed as an o This mechanism has an inherent problem.
intermediate. R Na + x
-

RX-1Mi
-

→
o The intermediate generated in the first step has 10 electrons around
o The first step is rate-determining. 杜乂一 + Nci carbon, violating the octet rule.

o The rate depends on the concentration of RX only. o Because two other mechanistic possibilities do not violate a
fundamental rule, this last possibility can be disregarded.
o The rate equation is first order.

7.9 Possible Mechanisms for Nucleophilic Substitution 33 7.9 Possible Mechanisms for Nucleophilic Substitution 34

Two Mechanisms for Nucleophilic Substitution Two Mechanisms for Nucleophilic Substitution
o One-step reaction (2nd order) or Two-step reaction (1st order)? o One-step reaction (2nd order) or Two-step reaction (1st order)?

o Kinetic data show that the rate of reaction 1 depends on the concentration of o Kinetic data show that the rate of reaction 2 depends on the concentration of
both reactants (thus 2nd order reaction), which suggests a bimolecular only the alkyl halide (thus, 1st order reaction).
reaction with a one-step mechanism. o This suggests a two-step mechanism in which the rate-determining step
o This is an example of an SN2 (substitution nucleophilic bimolecular) mechanism. involves the alkyl halide only.
o This is an example of an SN1 (substitution nucleophilic unimolecular)
mechanism.

7.10 Two Mechanisms for Nucleophilic Substitution 35 7.10 Two Mechanisms for Nucleophilic Substitution 36
 Two Mechanisms for Nucleophilic Substitution SN2 Reaction: kinetics
o SN2 reaction exhibits second-order kinetics: one-step mechanism
o Two well known mechanisms for nucelophilic substitution at an sp3
o Concerted reaction: bond breaking and bond making occur at the SAME time
hybridized carbon:

- SN2 mechanism (subsitution nucleophilic bimolecular)

- SN1 mechanism (subsitution nucleophilic unimolecular)

7.10 Two Mechanisms for Nucleophilic Substitution 37 7.11 The SN2 Mechanism 38

SN2 Reaction: stereochemistry SN2 Reaction: stereochemistry

o ALL SN2 reactions proceed with backside attack of the nucleophile, resulting
in inversion of configuration at a stereogenic center.
o The transition state always has partial bonds to the nucleophile and the
leaving group: partial charges on the nucleophile and/or leaving group.

7.11 The SN2 Mechanism 39 7.11 The SN2 Mechanism 40

 SN2 Reaction: R group SN2 Reaction: R group
o As the number of R groups on the carbon with the leaving group increases, the o The higher the Ea, the slower the reaction rate.
rate of an SN2 reaction decreases. (o Thus, any factor that increases E decreases the reaction rate.

1빤 )
이에 안감 '
a

SN2

o Methyl and 1º alkyl halides undergo SN2 reactions with ease.

o 2º Alkyl halides react more slowly.
o 3º Alkyl halides do not undergo SN2 reactions due to steric effects.
o Bulky R groups near the reaction site make nucleophilic attack from the
backside more difficult, slowing the reaction rate.
카본주변의 울퉁불퉁하면
할수록 잔 와가
1

7.11 The SN2 Mechanism 41 7.11 The SN2 Mechanism 42

SN2 Reaction: R group SN1 Reaction: kinetics

o Increasing the number of R groups on the carbon with the leaving group
o SN1 reaction exhibits first-order kinetics: more than one-step mechanism

i)
increases crowding in the transition state, thereby decreasing the rxn rate.
o The SN2 reaction is fastest with unhindered halides o The slow step, called rate-determining step, is unimolecular.

o Bond breaking occurs before bond making.

o Carbocations are formed as reactive intermediates.

하지만
불안정하긴 로자
0th 자연상에
안정)
☐t (
어느정도는

7.11 The SN2 Mechanism 43 7.13 The SN1 Mechanism 44

 "

SN1 Reaction: kinetics SN1 Reaction: stereochemistry

成飜汪f)
봄ft
얘가내려가는정도정

얘가蜈一
o Carbocation is sp2 hybridized and trigonal planar, and contains a vacant p
orbital extending above and below the plane.

M4의 門幽아래
ro
v
모두7상)
•

T. t n
ceodefii.at)

o There is no preference for nucleophilic attack from either direction, an equal

amount of the two enantiomers is formed—a racemic mixture.
빟 ↳ 결과
o This process is called racemization.

.si?Eiif
achiral

7.13 The SN1 Mechanism 45 7.13 The SN1 Mechanism 46

SN1 Reaction: stereochemistry SN1 Reaction: R group

o As the number of R group on the carbon with the leaving group increases, the
rate of an SN1 reaction increases.
o This trend is exactly opposite to that observed for the SN2 mechanism.
o This should be related to the stability of carbonation in the rate-determining
step.

7.13 The SN1 Mechanism 47 7.13 The SN1 Mechanism 48

 SN1 Reaction: Carbocation Stability
o The effect of the type of alkyl halide on SN1 reaction rates can be explained
by considering carbocation stability.
o Carbocations are classified as primary (1º), secondary (2º), or tertiary (3º),
based on the number of R groups bonded to the charged carbon atom.
SN1 Reaction: Carbocation Stability
o Inductive effects occur by the pull of electron density through σ bonds
caused by electronegativity differences between atoms.
따져뵈야람
ftp.leketonegativity
o Alkyl groups are electron donor groups that stabilize a positive charge
because they contain several σ bonds, each containing electron density.

o As the number of R groups increases, carbocation stability increases. o Alkyl groups are more polarizable than a hydrogen atom, and better able to
donate electron density.
o This really means relative stability.

t.me
안정화
r o In general, the more alkyl groups attached to a carbon with a positive charge,
o Two effects: inductive effects and hyperconjugation.
the more stable the cation will be. I 그룹 ↑ → ahoa.tn 안정

7.14 Carbocation Stability 49 7.14 Carbocation Stability 50

about.in 주위 metyd.IN
SN1 Reaction: Carbocation Stability 안정성 SN1 and SN2 Mechanisms
o Hyperconjugation is the spreading out of charge by the overlap of an empty p
orbital with an adjacent σ bond.

o This overlap delocalizes the positive charge on the carbocation over a larger
volume, thus stabilizing it.

o For example, (CH3)2CH+ can be stabilized by hyperconjugation, but CH3+

cannot .

7.14 Carbocation Stability ✗ 안정성에

51 7.14 Carbocation Stability 52
대한 이야기
 E가 비슷한 쪽의 구조를 따라간다
Hammond Postulate 중간전이상태의 구조는 Hammond Postulate: Endothermic Reaction
.

o The Hammond postulate relates reaction rate to stability.
o It provides a quantitative estimate of the energy of a transition state.
o The Hammond postulate states that the transition state of a reaction
resembles the structure of the species (reactant or product) to which it is
closer in energy.
o In an endothermic reaction, the transition state resembles the products more
than the reactants.
o Lowering the energy of the transition state decreases Ea, which increases the
reaction rate.
o In an endothermic reaction, the more stable product forms faster.

89얘도
바뀜

얘한테는 빋颱s
○
↳ Eled 바뀌면
영향을
거의

7.15 The Hammond Postulate 53 7.15 The Hammond Postulate 54

Hammond Postulate: Exothermic Reaction Hammond Postulate: SN1 Reaction

o In an exothermic reaction, the transition state resembles the reactants more
than the products.
o Lowering the energy of the product state has little or no effect on the
energy of the transition state, and thus the reaction rate is unaffected.
o In an exothermic reaction, the more stable product may or may not form
faster, since Ea is similar for both products.
o In the SN1 reaction, the rate determining step is the formation of the
carbocation, an endothermic process.
o According to the Hammond postulate, the stability of the carbocation
determines the rate of its formation.

7.15 The Hammond Postulate 55 7.15 The Hammond Postulate 56

 SN1 or SN2 ? SN1 or SN2 ?: Alkyl Halide
o The most important factor is the identity of the alkyl halide.

o Four factors are relevant in predicting whether a given reaction

is likely to proceed by an SN1 or an SN2 mechanism:

1. The alkyl halide—CH3X, RCH2X, R2CHX or R3CX

2. The nucleophile—strong or weak

3. The leaving group—good or poor

4. The solvent—protic or aprotic

7.17 When is the Mechanism SN1 or SN2? 57 7.17 When is the Mechanism SN1 or SN2? 58

SN1 or SN2 ?: Nucleophiles SN1 or SN2 ?: Nucleophiles

o The rate of the SN1 reaction is unaffected by the identity of nucleophiles. o The strong nucleophile favors an SN2 mechanism.
o The rate of the SN2 reaction is significantly affected by nucleophiles. "

o Strong nucleophiles (which usually bear a negative charge) present in high .is
ri
concentrations favor SN2 reactions.
o Weak nucleophiles, such as H2O and ROH favor SN1 reactions by decreasing
the rate of any competing SN2 reaction.
o The weak nucleophile favors an SN1 mechanism.
o Consider what happens when the 2º alkyl halide, which can react by either
mechanism, is treated with either the strong nucleophile HO¯ or the weak
nucleophile H2O. ⊖
있퍒 ↑
)
SN2로 갈수 얊뒤 雎站
.모든가능
SE
선호 ✗
I. 반응

7.17 When is the Mechanism SN1 or SN2? 59 7.17 When is the Mechanism SN1 or SN2? 60
 SN1 or SN2 ?: Leaving group SN1 or SN2 ?: Solvent

dngenbondingortlydwgenbondingxflbetg oap.in
o A better leaving group increases the rate of both SN1 and SN2 reactions.
나)
o Polar protic solvents like H2O and ROH favor SN1 reactions because the ionic
intermediates (both cations and anions) are stabilized by solvation.

o Polar aprotic solvents favor SN2 reactions because nucleophiles are not well
solvated, and therefore, are more nucleophilic.

Prob 7.39. Determine substitution mechanism, and solvent that affords the
faster reactions

H2O or
(CH3)3CBr + H2O → (CH3)3COH + HBr
(CH3)2C=O
di aw
)
(짝산의 pk걊
H2O or
+ –OH → + Br–
Br OH
H3 C H3 C
DMF

7.17 When is the Mechanism SN1 or SN2? 61 7.17 When is the Mechanism SN1 or SN2? 62

- 2쯰 '

SN1 or SN2 ? Vinyl and Aryl Halides

o SN1 or SN2 reactions occur only at sp3 hybridized carbons.

o Vinyl and aryl halides, which have a halogen attached to a sp2 hybridized
carbon, do not undergo SN1 or SN2 reactions.

o SN2: The higher s-character in sp2 hybrid orbital makes the bond shorter and
stronger.

o SN1: Heterolysis of the C-X bond would form a highly unstable vinyl or aryl
cation.

7.17 When is the Mechanism SN1 or SN2? 63 7.18 Vinyl Halides and Aryl Halides 64
 물질
물질의 전단계
Target
.

Organic Synthesis ㅎ
(역방향으로 가서 Organic Synthesis
전단계 )
↓ 시작물질을 찾기
전단계
:
o Organic synthesis is the systematic preparation of a compound from a readily
available starting material by one or many steps.

o Nucleophilic substitution reactions, especially SN2, are used to introduce a

wide variety of functional groups into a molecule, depending on the nucleophile.

o Organic synthesis has produced many useful compounds (e.g., pharmaceuticals,

pesticides, and polymers used in everyday life).

o Chemists may rely on synthesis to prepare useful substances such as a natural

product produced by organisms, but in only minute amounts (e.g., Taxol used in
cancer treatment).

7.19 Organic Synthesis 65 7.19 Organic Synthesis 66

Organic Synthesis Organic Synthesis

o To carry out the synthesis of a particular compound, we must think backwards,
and ask ourselves the question:
o “What starting material and reagents are needed to make it?”
o If a nucleophilic substitution is being used, determine what alkyl halide and
what nucleophile can be used to form a specific product.
o To determine the two components needed for synthesis, remember that the
carbon atoms come from the organic starting material, in this case, a 1° alkyl
halide.
o The functional group comes from the nucleophile, HO¯ in this case.
o With these two components, we can “fill in the boxes” to complete the
synthesis.

7.19 Organic Synthesis 67 7.19 Organic Synthesis 68

Summary of Ch 7
o General Feature of Alkyl Halides

o Nucleophilic Substitution: SN1 and SN2

- Mechanism (Kinetics)

- Alkyl Halides

- Stereochemistry

- Nucleophiles

- Leaving group

- Solvent

o Problems : 41, 44, 45, 47, 52, 55, 56, 59, 62, 64, 66, 70, 73, 74, 76, 77, 79
69