Prelim Exam 1: Review of Reactions; Chemistry of Benzene; Alcohols and Phenols; Ethers (Chem 322 - Organic Chemistry) Flashcards
1
Q
aromaticity
A
stability associated with benzene and related compounds that contain a cyclic conjugated system of 4n + 2 pi electrons
2
Q
electrophilic aromatic substitution
A
an electrophile (E+) reacts with an aromatic ring and substitutes for one of the hydrogens
3
Q
halogenation
A
substitution of a hydrogen on an aromatic ring with a halogen (-Cl, -Br, -I); occurs with the use of a catalyst or oxidizing agent
4
Q
nitration
A
substitution of a hydrogen on an aromatic ring with a nitro group (-NO2); added with H2SO4; nitro-substituted product can be reduced to yield an arylamine (ArNH2)
5
Q
sulfonation
A
substitution of a hydrogen on an aromatic ring with a sulfonic acid group (-SO3H); adding with fuming sulfuric acid (mixture of H2SO4 and SO3); is readily reversible and is favored in strong acid
6
Q
hydroxylation
A
substitution of a hydrogen on an aromatic ring with a hydroxyl group (-OH); added with catalyst p-hydroxyphenylacetate-3-hydroxylase, molecular oxygen and coenzyme reduced flavin adenine dinucleotide (FADH2)
7
Q
alkylation
A
substitution of a hydrogen on an aromatic ring with an alkyl group (-R); introduction of an alkyl group onto the benzene ring
8
Q
acylation
A
substitution of a hydrogen on an aromatic ring with an acyl group (-COR)
9
Q
Friedel-Crafts Reaction
A
alkylation reaction is carried out by treating an aromatic compound with an alkyl chloride (RCl) in presence of AlCl3 to generate a carbocation electrophile (R+) that loses a H+ to yield a substituted arene
10
Q
limitations of Friedel-Crafts Alkylation
A
- Only alkyl halides can be used… 2. not functional when the aromatic ring is substituted by a strong electron-withdrawing group (such as carbonyl) or by a basic amino group that can be protonated… 3. difficult to stop reaction after a single substitution (polyalkylation is favored)… 4. skeletal rearrangement of alkyl carbocation electrophile sometimes occurs during reaction (especially when using a primary alkyl halide)
11
Q
substituent effects on electrophilic aromatic substitution
A
affect reactivity, affect orientation of reaction
12
Q
activating groups
A
donate electrons to the ring, making the ring more electron-rich, stabilizing the carbocation intermediate, and lowering the activation energy for its formation
13
Q
deactivating groups
A
withdraw electrons from ring, making the ring more electron-poor, destabilizing the carbocation intermediate, and raising the activation energy for its formation
14
Q
inductive effect
A
withdrawal/donation of electrons through sigma bond due to electronegativity (withdrawal of electrons by halogens, hydroxyl groups, carbonyl groups, cyano groups, and nitro groups) (donation of electrons by alkyl groups)
15
Q
resonance effect
A
withdrawal/donation of electrons through a pi bond due to overlap of a p orbital on substituent with a p orbital on aromatic ring (withdrawal of electrons by carbonyl groups, cyano groups, and nitro groups) (donation of electrons by halogens, hydroxyl groups, and alkoxyl -OR groups)
16
Q
orientation of EAS reaction
A
nature of substituent initially present on benzene ring determines position of second substituent
17
Q
(Substituent Effects in EAS) CH3
A
activating; ortho/para-directing; weak donating inductive effect; no resonance effect
18
Q
(Substituent Effects in EAS) OH, NH2
A
activating; ortho/para-directing; weak withdrawing inductive effect; strong donating resonance effect
19
Q
(Substituent Effects in EAS) F, Cl, Br, I
A
deactivating; ortho/para-directing; strong withdrawing inductive effect; weak donating resonance effect
20
Q
(Substituent Effects in EAS) NO2, CN, CHO, CO2R, COR, CO2H
A
deactivating; meta-directing; strong withdrawing inductive effect; strong withdrawing resonance effect
21
Q
electron donating group
A
lone pairs of electrons on first atom
22
Q
electron withdrawing group
A
first atom is multiple bonded to a more electronegative atom
23
Q
electron withdrawing groups on aromatic rings
A
strong deactivators and meta directing: electron withdrawing inductive effect and electron withdrawing resonance effect
24
Q
electron donating groups (except halogens) on aromatic rings
A
strong activators and ortho/para directing: electron donating inductive effect and electron donating resonance effect
25
halogens on aromatic rings
weak deactivators and ortho/para directing: electron withdrawing inductive effect and electron donating resonance effect
26
if directing effects of two groups agree with each other
a singular aromatic substitution product is formed because further substitution is directed to same position
27
if directing effects of two groups oppose each other
a mixture of aromatic substitution products is formed, with the major product having further substitution at the point where the more powerful activating group directs it
28
further substitution between two groups in a meta-disubstituted compound
rarely occurs because of hindrance at the middle position
29
deactivating substituents on aromatic rings
prevent Friedel-Crafts alkylation/acylation
30
ortho-position is not favored
if ortho/para directing substituent is bulky (ex: NHOCH3, t-butyl group)
31
reactivity / influence on EAS of substituents on aromatic ring
strong deactivators (electron-withdrawing groups) < weak deactivators (halogens) < weak activators (aromatic ring / alkyl groups) < strong activators (electron donating groups except halogens)
32
nucleophile aromatic substitution (NAS)
a nucleophile (Nuc:-) reacts with aromatic ring and substitutes for an attached halide/leaving group; occurs only if aromatic ring has an electron-withdrawing substituent in ortho/para position to the leaving group (to stabilize the anion intermediate through resonance) and is thus favored by electron-withdrawing substituents (which activate the rings in this process, compared to electron-donating groups that activate in EAS)
33
electron-withdrawing groups in NAS
ortho/para directing
34
benzyne
a highly reactive intermediate in some nucleophilic aromatic substitutions that has a benzene ring with a formal triple bond (from removal of two hydrogens); the triple bond uses sp^2 hybridized carbons instead of sp; there is one pi bond formed from p-p overlap and one pi bond formed from sp^2-sp^2 overlap
35
oxidation of alkyl side chains on aromatic compounds
uses KMnO4, H2O... involves reaction of CH bonds at position next to aromatic ring (can only occur if benzylic hydrogens are present)
36
bromination of alkylbenzene side chains
uses NBS... only occurs at benzyllic position (no mixture of products)
37
selective reduction of alkene on side chain of aromatic compound
uses H2, Pd/C... reduces alkene only
38
hydrogenation of aromatic ring
uses Pt/C or Rh/C (most effective)... reduces aromatic compound to cyclic compound with no multiple bonds
39
reduction of aryl alkyl ketones
uses H2, Pd/C (after original Friedel-Crafts acylation reaction)... converts any alkyl ketone prepared by Friedel-Crafts acylation into an alkylbenzene, avoiding carbocation rearrangement issues from using a primary alkyl halide; not compatible with presence of NO2 because NO2 is reduced to NH2 under these reaction conditions
40
limitations of Friedel-Crafts Reactions
cannot occur on strongly deactivated rings; will not work is amine is present; polyalkylation will occur without use of excess benzene; rearrangement of alkyl groups occurs
41
Br2/FeBr3
brominating agent that introduces a bromine onto an aromatic ring
42
Cl2/FeCl3
chlorinating agent that introduces a chlorine onto an aromatic ring
43
I2/CuCl2
iodizing agent that introduces an iodine onto an aromatic ring
44
HNO3/H2SO4
nitrating agent that introduces a nitro group onto an aromatic ring
45
SO3/H2SO4
sulfonating agent that introduces a sulfonic acid onto an aromatic ring
46
RCl/AlCl3
alkylating agent that introduces an alkyl group onto an aromatic ring
47
RCOCl/AlCl3
acylating agent that introduces an acyl group onto an aromatic ring
48
1. Fe, H3O+ ; 2. HO-
reducing agent that reduces a nitro group on a benzene to an amine group
49
NaOH, H2O
substitutes an aryl halide for an hydroxyl group on an activated aromatic ring
50
NaNH2, NH3
substitutes an aryl halide for an amine group (through a benzyne intermediate) on an unactivated aryl halide
51
KMnO4 (H2O) (hot, concentrated)
oxidizing agent that converts alkylbenzenes to benzoic acid derivatives (converts an alkyl group to a carboxylic acid)
52
NBS
brominates an alkylbenzene side chain (only if a benzylic hydrogen is present)
53
H2, Rh/C
catalytically hydrogenates a benzene ring to its saturated cyclohexane
54
H2, Pd/C
reducing agent that reduces an aryl alkyl ketone to a alkyl group and reduces a nitro group to an amine group
55
Zn(Hg)/HCl
reducing agent that converts a carbonyl group of an aldehyde/ketone to a methylene (CH2) group
56
where a substituent directs further substitution is dependent upon/due to
charged positions on resonance structures of benzene; due to stability of carbocation intermediates
57
H3O+
removes sulfonic acid groups from aromatic ring
58
SO3H
used as a blocking substituent when trying to direct further substitution to a specific position (then later removed)
59
Mg
addition to a benzene with a halide yields a Grignard reagent (which is a good nucleophile)
60
1. NaOH; 2. H+
converts a sulfonic acid group on a benzene to an hydroxyl group
61
bulky substituent
when substituent is branched at first point of attachment to aromatic ring
62
add blocking group
when only ONE product is desired (and not wanting to separate out mixtures)
63
alcohol
compounds that have OH bonded to a saturated, sp^3 hybridized carbon atom
64
enol
compounds that have OH bonded to a vinylic, sp^2 hybridized carbon
65
phenol
OH bonded to a carbon involved in an aromatic benzene ring
66
primary alcohol
an alcohol in which the hydroxyl (-OH) group is attached to a carbon that is attached to no more than one other carbon.
67
secondary alcohol
An alcohol in which the hydroxyl (-OH) group is attached a carbon that is attached to two other carbons.
68
tertiary alcohol
An alcohol in which the hydroxyl (-OH) group is attached to a carbon that is in turn attached to three other carbons.
69
alcohol nomenclature
1. select longest carbon chain containing hydroxyl group and derive parent name by replacing -e ending with -ol... 2. number chain beginning at end nearest to hydroxyl group... 3. number substituents according to position on chain and write the name, listing substituents in alphabetical order and identifying position to which OH is bonded
70
phenol nomenclature
"phenol" as parent name and applicable numbering of substituents when present
71
properties of alcohols and phenols
higher boiling points due to hydrogen bonding; weakly basic and weakly acidic (as weak bases, they are reversibly protonated by strong acids to yield oxonium ion ROH2+ / as weak acids, they dissociate slightly in dilute aqueous solution by donating a proton to water to yield H3O+ and alkoxide ion RO- or phenoxide ion ArO-)
72
smaller Ka/larger pKa
weaker acid
73
larger Ka/smaller pKa
stronger acid
74
the more readily the alkoxide ion is solvated by H2O then
the more stable it is, the more its formation is energetically favored, and the greater the acidity of the parent alcohol
75
electron withdrawing substituents stabilize an alkoxide ion
through inductive effect, making the alcohol more acidic
76
phenols are more acidic than alcohols
because conjugate base phenoxide ion is resonance stabilized, allowing for negative charge to be delocalized over ortho and para positions
77
phenols are more acidic with
electron withdrawing substituents
78
phenols are less acidic with
electron donating substituents
79
1. BH3, THF
2. H2O2, -OH
converts an alkene into an alcohol through syn, non-Markovnikov addition product
80
1. Hg(OAc)2, H2O
2. NaBH4
converts an alkene into an alcohol through markovnikov addition product
81
1. OsO4, pyridine
2. NaHSO3, H2O
converts an alkene into a diol through syn addition (creating cis product)
82
1. RCO3H, CH2Cl2 [MCPBA]
2. H3O+
converts an alkene into a diol through an epoxide intermediate then anti addition (creating trans product)
83
for nucleophilic aromatic substitution
must have electron withdrawing group either ortho or para
84
priority groups in nomenclature
alcohol > alkenes, alkynes > alkyl halogens
85
highest priority group
has the ending in the name
86
reduction of aldehydes using 1. NaBH4 2. H3O+ or 1. LiAlH4 2. H3O+
produces primary alcohol
87
reduction of ketones using 1. NaBH4 2. H3O+ or 1. LiAlH4 2. H3O+
produces secondary alcohol
88
reduction of carboxylic acids or esters using 1. LiAlH4 2. H3O+
produces primary alcohol
89
reduction of carbonyl compounds using 1. RMgX 2. H3O+ (Grignard reaction)
react with formaldehyde to give primary alcohols, aldehydes to give secondary alcohols, and with ketones to give tertiary alcohols, esters to give tertiary alcohols
90
grignard reagent limitations
grignard reagent cannot be prepared from an organohalide if other functional groups are present in same molecules
91
hydrogen bond donor
molecule/ion that donates H in hydrogen bond
92
hydrogen bond acceptor
molecule/ion that binds to donated H
93
reaction of tertiary alcohol with HX through Sn1 mechanism
replaces OH with X
94
reaction of primary or secondary alcohol with SOCl2 and PBr3 through Sn2 mechanism
replaces OH with Cl or Br
95
1. p-TosCl, pyridine
reaction of alcohol with p-TosCl in pyridine solution to yield alkyl tosylates (ROTos) through Sn2 mechanism
96
reaction of tertiary alcohols with H3O+, THF through E1 reaction
follow Zaitsev's rule to yield more stable alkene
97
reaction of alcohols with POCL3, pyridine through E2 reaction
yields more stable alkene
98
reaction of 1. SOCl2 2. alcohol with carboxylic acids
yields esters
99
DMP with primary alcohol
yields aldehyde
100
DMP with secondary alcohol
yields ketone
101
CrO3, H3O+ with primary alcohol
yields carboxylic acid
102
Na2Cr2O7 with secondary alcohol
yields ketone
103
hydride (H:-) reagents
lithium aluminum hydride LiAlH4 -- more reactive; sodium borohydride NaBH4 -- less reactive
104
R:- reagent
RMgX (grignard reagent)
105
alcohols are good solvents
due to low reactivity properties
106
alcohol reactivity can be increased by
protonation so that the ROH becomes ROH2 and thus OH2 is a leaving group; deprotonation so that ROH becomes RO- and a good nucleophile
107
protecting interfering functional group
1. introduce a protecting group to block interfering function... 2. carry out desired reaction... 3. remove protecting group
108
protecting alcohol in grignard reaction using protecting route
1. protect alcohol by adding (CH3)3SiCl, (CH3CH2)3N to yield TMS ether... 2. form grignard reagent... 3. do grignard reaction... 4. remove protecting group by adding H3O+
109
oxidizing agents converting primary alcohols to aldehydes
PCC, DMP
110
oxidizing agents converting primary alcohols to carboxylic acids
KMnO4, CrO3, Na2Cr2O7, or HNO3
111
oxidizing agents converting secondary alcohols to ketones
PCC, DMP, KMnO4, CrO3, Na2Cr2O7, or HNO3
112
oxidation of tertiary alcohol
CANNOT OCCUR, no reaction
113
electrophilic aromatic substitution reactions of phenols
hydroxyl group is strongly activating and ortho/para directing; highly reactive substrates for electrophilic halogenation/nitration/sulfonation/Friedel-Crafts reactions
114
oxidation of phenols to quinones
Na2Cr2O7, H2O
115
infrared spectroscopy of alcohols
characteristic C-O absorption at 1500 cm^-1; characteristic OH absorption 3300-3600 cm^-1
116
infrared spectroscopy of phenols
characteristic broad absorption 3500 cm^-1 due to OH; absorption at 1500-1600 cm^-1 for aromatic
117
NMR spectroscopy of alcohols
3.4-4.5 delta chemical shifts (C-O)
118
NMR spectroscopy of phenols
7-8 delta chemical shifts (aromatic ring); 3-8 delta chemical shifts (phenol OH)
119
1. NaBH4 (or LiAlH4) 2. H3O+
synthesis of alcohols from aldehydes or ketones
120
1. LiAlH4 2. H3O+
synthesis of alcohols from esters or carboxylic acids
121
1. RMgX 2. H3O+
synthesis of alcohol from aldehydes, ketones, or esters
122
dehydration with H3O+
converts tertiary alcohols to alkene
123
dehydration with POCl3, pyridine
converts secondary and tertiary alcohols to alkene
124
DMP or CrO3
oxidation of primary alcohols to aldehyde or carboxylic acid (respectively)
125
DMP
oxidation of secondary alcohol to ketone
126
Na2Cr2O7, H2O
oxidation of phenol to quinone
127
primary alcohols cannot be dehydrated to form alkene
because they undergo substitution
128
add -CH2-CH2-O in one step of synthesis
use an epoxide ring with grignard reagent and H3O+; can only be used if desired product has OH attached to -CH2-CH2- without branching on any of the CH2
129
1. ethylene oxide 2. H3O+
adds CH2-CH2-O to grignard reagent
130
grignard limitation
cannot have OH or NH present with grignard
131
1. TMSCl, N(CH2CH3)3 2. H3O+
provides alcohol protection through conversion of the alcohol into TMS ether, then deprotected using H3O+
132
double ended grignard reagent
cannot be smaller than a two carbon chain between grignard reagent ends
133
ethers (ROR)
organic derivatives of water with two organic groups bonded to the same oxygen atom, with the organic groups being either alkyl, aryl, or vinylic and the oxygen atom being in an open chain or a ring
134
thiols (RSH)/sulfides (RSR)
sulfur analogs of alcohols and ethers
135
ether nomenclature
simple ethers with no functional groups are named by identifying organic substituents and adding word "ether"; if other functional groups are present then the ether part is considered an alkoxy substituent
136
properties of ethers
have nearly the same geometry as water: approximately a tetrahedral bond angle and oxygen is sp^3 hybridized; electronegative oxygen gives compound a slight dipole moment so boiling points are often slightly higher than alkane counterparts; relatively stable and unreactive; can react slowly with oxygen in air to give peroxides (compounds with O-O bond)
137
williamson ether synthesis
alkoxide ion reacts with a primary alkyl halide to tosylate in an Sn2 reaction; unsymmetrical ethers should be synthesized from reaction between more hindered alkoxide partner and less hindered halide partner; primary halides and tosylates work best because E2 competition can occur with more hindered substrates; reagents: 1. NaH, THF 2. RX
138
alkoxymercuration of alkenes
alkene is treated with alcohol in presence of mercuric acetate or (CF3CO2)2Hg, followed by reaction with NaBH4 to yield ether; markovnikov addition of alcohol to alkene; primary/secondary/tertiary alcohols react well but ditertiary ethers cannot be prepared due to steric hindrance; reagents: 1. (CF3CO2)2Hg, alcohol 2. NaBH4
139
naming ethers
alkyl alkyl ether or alkoxyalkane
140
tetrahydrofuran (THF)
polar aprotic solvent (has a dipole moment)
141
H2SO4
forms ethers from primary alcohols
142
(williamson ether synthesis) more sterically hindered part of ether
the alkoxide part
143
(williamson ether synthesis) less sterically hindered part of ether
the alkyl halide part
144
(alkoxymercuration) more sterically hindered part of ether
the alkene part
145
(alkoxymercuration) less sterically hindered part of ether
the alcohol part
146
acidity increases if negative charge of conjugate base
can be spread out/delocalized (which is better with electron-withdrawing groups)
147
alcohol acidity increases if additional electronegative atoms are present because
they delocalize the negative charge by induction
148
alcohols with the electron withdrawing group closer to the OH group
have increased acidity
149
alcohols with more electron withdrawing groups
have increased acidity
150
alcohols with the more electronegative electron withdrawing group
have increased acidity
151
electron withdrawing group on phenol
increases ring's ability to delocalize the negative charge, making the phenol more acidic
152
electron donating group on phenol
decreases ring's ability to delocalize the negative charge, making the phenol less acidic
153
electron withdrawing group is ortho/para to OH group on phenol
the phenoxide negative charge is further delocalized in an additional resonance structure, further increasing the phenol's acidity
154
electron donating by induction
alkyl groups
155
electron withdrawing by induction, electron donating by resonance
electron donating groups (groups with lone pair of electrons on first atom) and halogens
156
electron withdrawing by induction, electron withdrawing by resonance
electron withdrawing groups (groups where the first atom is multiple bonded to a more electronegative atom, no lone pairs on first atom)
157
pi bond breaks in step 1
EAS (electrophilic aromatic substitution) and EA (electrophilic addition)
158
sigma bond breaks in step 2
EAS (electrophilic aromatic substitution)
159
nucleophile adds to a pi bond in step 1
neither Sn1, EAS, or EA
160
reaction passes through a carbocation intermediate
Sn1, EAS, and EA
161
reducing SO3H to OH
H2, Pd
162
reducing carbonyl group to alkyl group
1) -OH 2) H3O+
163
carboxylic acid substituent on phenol
makes phenol more acidic; is the most acidic substituent possible
164
least nucleophilic aromatic ring
the ring that has an electron withdrawing group (that is strongly deactivating)
165
alkoxymercuration to yield ethers
the alcohol attacks the most substituted end of the starting alkene
166
when adding a primary group from friedel-crafts
the primary carbocation will rearrange to form the more stable secondary/tertiary carbocation if possible
167
ether properties
not an acid; weak base; poor nucleophile; poor electrophile
168
epoxide
three membered rings with one oxygen and two carbons to make a cyclic ether
169
preparation of epoxide
MCPBA
170
acid-catalyzed epoxide opening using H3O+ or HX
if a tertiary epoxide carbon is present, nucleophilic attack occurs primarily at the tertiary position in Sn1 manner; if no tertiary epoxide carbon, nucleophile attack occurs at least hindered site (primary) in Sn2 manner
171
base-catalyzed epoxide opening using -OH, -OR, R2NH, RMgX
if a tertiary epoxide carbon is present, nucleophilic attack occurs primarily at the tertiary position in Sn1 manner; if no tertiary epoxide carbon, nucleophile attack occurs at least hindered site (primary) in Sn2 manner
172
ether cleavage using HBr or HI
Sn2: if no tertiary, allylic, or benzylic carbons are attached to oxygen, attack occurs at least hindered carbon (methyl, primary, or secondary) [yields methyl/primary/secondary alkyl halide and primary/secondary alcohol]; Sn1: if tertiary, allylic, or benzylic carbons are attached to oxygen, attack occurs at more hindered carbon [yields tertiary/allylic/benzylic alkyl halide and primary/secondary/methyl alcohol]
173
the closer the substituent position
the stronger inductive effects (the stronger the acid)
174
alcohol protection
1. TMSCl 2. "reaction" 3. H3O+ to remove TMS group
175
more nucleophile benzene substituent
stronger activator
176
least nucleophile benzene substituent
stronger deactivator
177
benzoic acid
COOH on benzene
178
benzaldehyde
benzene with aldehyde
179
aniline
benzene with NH2
180
nitrobenzene
Benzene NO2
181
toluene
benzene with CH3
182
halobenzene
Benzene ring w/ an halide attached
