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CHM'224'•'Organic'Chemistry'IISpring'2013,'Des'Plaines'•'Prof.'Chad'Landrie
Alcohols:•Prepara'on*by*Addi'on*of*Organometallics*(17.5,*10.6,*19.7)
•Protec'on*(17.8)•Phenols*(17.9)
Lecture'2:'January'17,'2013
© 2013, Dr. Chad L. LandrieOrganic Chemistry II (CHM 224)
Slide Lecture 2: January 17
Nucleophiles
4
Nuc E X Nuc E + X
Nucleophiles Add to Electrophiles
• nucleophiles are Lewis bases
• they contain pairs of electrons (usually lone pairs, but not always)
• donate electron pairs to form covalent bonds with electrophilic atoms other than H.
• not all Lewis bases form covalent bonds
© 2013, Dr. Chad L. LandrieOrganic Chemistry II (CHM 224)
Slide Lecture 2: January 17
Anionic.Nucleophiles
5
Nuc E X Nuc E + X
Nucleophiles Add to Electrophiles
H3C O
O
O
carboxylate alkoxide hydrogen sulfide
hydroxide cyanideazide
H S
H O N N N N C
• many nucleophiles are anionic (negative charge)
• nulceophilic atom (one forming new bond) highlighted in red
© 2013, Dr. Chad L. LandrieOrganic Chemistry II (CHM 224)
Slide Lecture 2: January 17
Anionic.Nucleophiles
6
Nuc E X Nuc E + X
Nucleophiles Add to Electrophiles
anionic nucleophiles are often used/written as their metal salts
H3C ONa
O
OK
carboxylate alkoxide hydrogen sulfide
hydroxide cyanideazide
H SNa
H ONa N N NK N CNa
© 2013, Dr. Chad L. LandrieOrganic Chemistry II (CHM 224)
Slide Lecture 2: January 17
Electrophiles
7
Nuc E X Nuc E + X
Nucleophiles Add to Electrophiles
• electrophiles are Lewis acids other than H.
• accept electron pairs to form covalent bonds with nucleophiles
• usually contain a polar covalent bond where one atom is a good leaving group
• not all Lewis acids form covalent bonds
© 2013, Dr. Chad L. LandrieOrganic Chemistry II (CHM 224)
Slide Lecture 2: January 17
Electrophiles
8
Nuc E X Nuc E + X
Nucleophiles Add to Electrophiles
E Xδ+ δ+
polar covalent bond when X is strongly
electronegative
H3C Clδ+ δ+
alkyl halides are electrophiles; C of C-X bond, specifically
– –
carbonyl carbons are electrophiles; c-atom is partially +/vely charged
C
Oδ+
δ−
C
O
CHM'224'•'Organic'Chemistry'IISpring'2013,'Des'Plaines'•'Prof.'Chad'Landrie
Sec'on*17.5,*10.6,*19.7
PreparaHon'of'Alcohols'by'AddiHon'of'Organometallics
© 2013, Dr. Chad L. LandrieOrganic Chemistry II (CHM 224)
Slide Lecture 2: January 17
Grignard.Reac1on
10
nucleophilic additionAlkoxide
protonationAlcohol
Victor Grignard1912 Nobel Prize
R MgBr CO
+ CO
R
Mg Br H3O+COH
R(diethyl ether)
O
(THF: tetrahydrofuran)
Oor
Grignard Reagent:Alkyl magnesium halide;
nucleophile
Carbonyl:Ketone, Aldehyde or Ester;
electrophile
© 2013, Dr. Chad L. LandrieOrganic Chemistry II (CHM 224)
Slide Lecture 2: January 17
Grignard.Reagents
11
Br
Cl
+ Mg0 (metal)
+ Mg0 (metal)
MgBrEt2O
MgClTHF
• magnesium metal (Mg0) added to aryl and alkyl bromides and chlorides
• ethers are used as solvents; stabilize reagent• magnesium metal coated with MgO which is unreactive; must cut
metal fresh to expose unoxidized surface
We will not discuss the mechanism. It’s a radical mechanism involving single electron transfer (SET) from Mg0 to the halide.
© 2013, Dr. Chad L. LandrieOrganic Chemistry II (CHM 224)
Slide Lecture 2: January 17
Grignards.are.Nucleophiles.and.Strong.Bases
12
C MgClδ+δ−
C MgCl+−
• C-Mg bond is highly polar-covalent; it is covalent though, not ionic• the electron density in the C-Mg bond lies almost entirely on C; the carbon
atom is the nucleophile in a Grignard reagent• Grignards are very basic and must be prepared in dry environments to
prevent reaction with water (Glassware and solvents must be thoroughly dried! The reaction must be protected from atmospheric moisture!)
• Grignards are not compatible with protic functional groups such as alcohols
H3C MgBr + H2O CH4 + OH—
H3C MgBr + CH3CH3OH CH4 + CH3CH2O—
+ MgBr+
+ MgBr+
© 2013, Dr. Chad L. LandrieOrganic Chemistry II (CHM 224)
Slide Lecture 2: January 17
Board.Work:.Grignard.Mechanism
13
© 2013, Dr. Chad L. LandrieOrganic Chemistry II (CHM 224)
Slide Lecture 2: January 17
Examples.of.Grignards
14
O1. CH3CH2MgBr diethyl ether
2. H3O+/H2O
OH
H
O
2. H3O+/H2O
MgBr1. HO H
H H
O
2. H3O+/H2O
1. MgClTHF OH
OCO 2. H3O+/H2O
1.THF
MgBrO
OH
ketone 3º alcohol
aldehyde 2º alcohol
formaldehyde 1º alcohol
carbon dioxide
carboxylic acid
© 2013, Dr. Chad L. LandrieOrganic Chemistry II (CHM 224)
Slide Lecture 2: January 17
Grignards.in.Synthesis
15
HO H
BrMg
O
H +O
H+MgBr
2º Alcohols by Two Pathways
OHO
O
? O
OOH
Homologation (Chain Extension) of Alcohols
O
O O
H
HMgBr
+O
O
Br
PBr3
Mg, ether
ether
© 2013, Dr. Chad L. LandrieOrganic Chemistry II (CHM 224)
Slide Lecture 2: January 17
Prepara1on.of.Propargyl.Alcohols
16
H
a. NaNH2, NH3b. then add carbonyl:
c. H3O+/H2O
H3C CH3
O OHCH3
CH3
Bases Commonly Used to Deprotonate Alkynes
N
Li+LDA: lithium
diisopropyl amide
n-butyllithium(n-BuLi)Li
NaNH2 sodium amide
Anatomy of Alkenes and Alkynes
H3C
H H
CH3
vinylic allylic homoallylic
H H
CH3H3C
H
H
acetylenic
propargylic homopropargylic
CHM'224'•'Organic'Chemistry'IISpring'2013,'Des'Plaines'•'Prof.'Chad'Landrie
17.8
ProtecHon'of'Alcohols
© 2013, Dr. Chad L. LandrieOrganic Chemistry II (CHM 224)
Slide Lecture 2: January 17
Silyl.Protec1ng.Groups
19
A protecting group is a temporary functional group that is unreactive toward the desired reactions conditions and can be easily removed to reveal the original functional group.
O BrSiHO Brtrimethylsilyl chloride (TMSCl)
or chlorotrimethylsilane
(CH3CH2)3N
(CH3)3SiCl
alcohol silyl ether
Step One: Protection
• silanes are common protecting group for alcohols• need an amine base like triethylamine (TEA) to neutralize HCl produced; HCl
would react with the silyl ether to give the alcohol back• silyl ethers are sensitive to acids and are not compatible with acidic reactions• silyl ethers are stable (do not react) under basic conditions like Grignard reaction
© 2013, Dr. Chad L. LandrieOrganic Chemistry II (CHM 224)
Slide Lecture 2: January 17
Silyl.Protec1ng.Groups
20
Step Two: Reaction
O BrSi
1. Mg, ether
2.
3. H3O+/H2O
H
O
OSiOH
If a strong enough acid is used in the third step, the silyl group may be removed here at the same time as protonation of the alkoxide intermediate
Step Three: Deprotection
OSiOH H3O+/H2O
or commonly fluoride (F–) reagents:e.g., tetrabutyl ammonium fluoride (TBAF)
HO
OH
• F and Si form very strong bonds, strong than O and Si• fluoride undergoes SN2 on Si to break Si-O bond
CHM'224'•'Organic'Chemistry'IISpring'2013,'Des'Plaines'•'Prof.'Chad'Landrie
17.9
Phenols'and'Their'Uses
© 2013, Dr. Chad L. LandrieOrganic Chemistry II (CHM 224)
Slide Lecture 2: January 17
Phenols
22
∆9-tetrahydrocannibol (THC)psychoactive component of marijuana
cannabis sativa
© 2013, Dr. Chad L. LandrieOrganic Chemistry II (CHM 224)
Slide Lecture 2: January 17
Naturally.Occurring.&.Synthe1c.Phenols
23
morphine(analgesic)
serotonin(neurotransmitter)
dopamine(neurotransmitter)
∆9-tetrahydrocannibol (THC)psychoactive component of marijuana
© 2013, Dr. Chad L. LandrieOrganic Chemistry II (CHM 224)
Slide Lecture 2: January 17
Phenols.in.the.Lab:.Phenophthalein
24
• conjugated π-systems are often chromophores
• chromophores can absorb visible light and promote a π-electron to an excited state
• basic solutions deprotonate phenolphthalein, creating a fully conjugated π-system that absorbs blue light (red more visible)
all π-systems not fully conjugatedoes not absorb visible light (colorless)
π-systems are fully conjugateabsorbs blue light (pink)
pH = 0-8.2 pH = 8.2-12
© 2013, Dr. Chad L. LandrieOrganic Chemistry II (CHM 224)
Slide Lecture 2: January 17
Phenols.in.Synthesis
25
OCH3
OHOCH3
HO
HO
combretastatin A4combretastatin A1
OCH3
OHOCH3
HO
HO
OH
Combretum caffrumAfrican bush willow
Biological Activity
• tubulin inhibitors = tumor cell occlusion
• selective vascular-disrupting agents = hypoxia of tumor cells
• cytotoxicity against human cancer cell lines
• nitrogen analogues may be significantly more potent
© 2013, Dr. Chad L. LandrieOrganic Chemistry II (CHM 224)
Slide Lecture 2: January 17
Phenols.in.Synthesis
26
O
1. n-BuLi, Ti(OPri)4 THF, 50 ºC, 48 h 2. H2O
O
PSDVB
HOCl
PSDVB +
immobilization
Merrifield Resin 4-(phenylethynyl)phenol (PEP)
combretastatin A1
OCH3
OHOCH3
HO
HO
OH
PSDVB
Landrie, C.L. et al. Reduction of Solid-Supported Olefins and Alkynes. J. Org. Chem. 74, 9535-9538 (2009).
Stereoselective Reduction of An Alkyne to a cis-Alkene(Research conducted by undergraduate students)
© 2013, Dr. Chad L. LandrieOrganic Chemistry II (CHM 224)
Slide Lecture 2: January 17
Nomenclature
27
• Historical name for benzene was phene.• Phenol is the preferred IUPAC & 2004 parent name for hydroxybenzene
derivatives• Substituents listed in alphabetical order; C-1 bears hydroxyl group.• Follow first point of difference rule when two sets of locants are possible.• Do not use CIP rules to determine locants for aromatic systems.
© 2013, Dr. Chad L. LandrieOrganic Chemistry II (CHM 224)
Slide Lecture 2: January 17
Choose the locant set with the lowest value at the first point of difference.
Nomenclature
28
1
4-bromo-2-ethyl-6-isopropyl
4-bromo-6-ethyl-2-isopropyl
X
√
OH
Br4
Remember: Substituents must be listed in increasing alphabetical order
© 2013, Dr. Chad L. LandrieOrganic Chemistry II (CHM 224)
Slide Lecture 2: January 17
Nomenclature
29
Common Names for Benzenediols
© 2013, Dr. Chad L. LandrieOrganic Chemistry II (CHM 224)
Slide Lecture 2: January 17
Quick.Review:.Benzene
30
C–C bond length: 150 pmC=C bond length: 134 pm
All bonds = 140 pm
H
H
HH
HH H
H
HH
H
H
Predicted Actual
Instead of alternating single and double bonds, all of the C-C bonds in benzene are the same length.
© 2013, Dr. Chad L. LandrieOrganic Chemistry II (CHM 224)
Slide Lecture 2: January 17
Resonance.Formula1on.of.Benzene
31
The structure of benzene is best represented, not as an equilibrium between two isomers, but as a resonance hybrid of two Lewis
structures.
HH
HH
H
HH
H
HH
H
H
Electrons are not localized in alternating single and double bonds, but are delocalized over all six ring carbon atoms.
© 2013, Dr. Chad L. LandrieOrganic Chemistry II (CHM 224)
Slide Lecture 2: January 17
Structure.&.Bonding.in.Phenol
32
• Phenol is planar• Bond angles around oxygen are nearly tetrahedral• The C–O bond in phenol is shorter than in methanol.• Why?
© 2013, Dr. Chad L. LandrieOrganic Chemistry II (CHM 224)
Slide Lecture 2: January 17
Structure.&.Bonding.in.Phenol
33
Q: Why is the C–O bond in phenol shorter than the C–O bond in methanol?
A1: The carbon in phenol is sp2-hybridized and has more s-character than the sp3-hybridized carbon in methanol. An orbital with more s-character exhibits better overlap and gives stronger σ-bonds.
sp2 sp3
© 2013, Dr. Chad L. LandrieOrganic Chemistry II (CHM 224)
Slide Lecture 2: January 17
Hybridiza1on.Effects.Degree.of.Orbital.Overlap
34
pure p
sp3
sp2
sp
pure s
• Electrons are diffuse, spreadout throughout the molecular orbital.
• As s-character increases, the percentage of overlap compared to the rest of the MO increases.
• A greater percentage of overlap means greater electron density between the atoms.
• More electron density between the two nuclei = stronger bond.
overlap
© 2013, Dr. Chad L. LandrieOrganic Chemistry II (CHM 224)
Slide Lecture 2: January 17
Structure.&.Bonding.in.Phenol
35
Q: Why is the C–O bond in phenol shorter than the C–O bond in methanol?
A2: Resonance delocalization of oxygen’s lone-pair with the aromatic π-system leads to partial double-bond character for the C-O bond. This bond is thus stronger and shorter.
© 2013, Dr. Chad L. LandrieOrganic Chemistry II (CHM 224)
Slide Lecture 2: January 17
Structure.&.Bonding.in.Phenol
36
• These structural features are responsible for the physical and chemical properties of phenol.
• The phenol oxygen is less basic than in alcohols.• Phenols are more acidic than alcohols.• SArE is faster, especially at ortho and para positions due to electron
donation by the hydroxyl group.
CHM'224'•'Organic'Chemistry'IISpring'2013,'Des'Plaines'•'Prof.'Chad'Landrie
17.9;*Review*Ch.*2
Physical'and'AcidMBase'ProperHes'of'Phenols
© 2013, Dr. Chad L. LandrieOrganic Chemistry II (CHM 224)
Slide Lecture 2: January 17
Physical.Proper1es
38
Phenols have:• higher m.p.s• higher b.p.s• higher water
solubility
© 2013, Dr. Chad L. LandrieOrganic Chemistry II (CHM 224)
Slide Lecture 2: January 17
Physical.Proper1es
39
Each trend explained by hydrogen bonding:
• increased intermolecular H-bonding = higher crystal lattice energy (m.p.)
• = lower Pº = higher b.p.
• increased intermolecular H-bonding with water = increased solubility
© 2013, Dr. Chad L. LandrieOrganic Chemistry II (CHM 224)
Slide Lecture 2: January 17
Physical.Proper1es
40
Ortho-nitro substituted phenols generally have lower melting and boiling points than meta and para substituted phenols.
m.p. = 46 ºCb.p. = 215 ºC(@ 760 Torr)
m.p. = 97 ºCb.p. = 194 ºC(@ 70 Torr!)
• increased intramolecular H-bonding in ortho =
• decreased intermolecular bonding
• = lower crystal lattice energy
• = higher Pº
© 2013, Dr. Chad L. LandrieOrganic Chemistry II (CHM 224)
Slide Lecture 2: January 17
Physical.Proper1es:.Acidity
41
• Phenols are more acidic than alcohols but less acidic than carboxylic acids.• Electron delocalization stabilizes the phenoxide conjugate base.
pKa = 4.7+ +
Res
onan
ce
Stab
iliza
tion
© 2013, Dr. Chad L. LandrieOrganic Chemistry II (CHM 224)
Slide Lecture 2: January 17
Physical.Proper1es:.Acidity
42
• Phenols are more acidic than alcohols but less acidic than carboxylic acids.• Electron delocalization stabilizes the phenoxide conjugate base.
Electron density is delocalized onto the ortho and para carbons only.
© 2013, Dr. Chad L. LandrieOrganic Chemistry II (CHM 224)
Slide Lecture 2: January 17
Physical.Proper1es:.Acidity
43
Conjugate bases stronger than phenoxide (whose conjugate acids are weaker than phenol) react nearly completely with phenols.
© 2013, Dr. Chad L. LandrieOrganic Chemistry II (CHM 224)
Slide Lecture 2: January 17
AcidPBase.Equilibria:.Determining.the.Direc1on.of.AcidPBase.Reac1ons
44
You must identify the ACID on each side of the equilibrium:pKeq = pKa (acid left) - pKa (acid right)
Keq = 10-[pKa (acid left) - pKa (acid right)]
• remember: p = -log10
• this equation works for any acid-base reaction; doesn’t matter which way equilibrium is written
Keq = 10-[10 - 15.7] = 10-[-5.7] =105.7
Example:
Acid-base equilibria always lie to the side with weaker conjugate acids and bases.
© 2013, Dr. Chad L. LandrieOrganic Chemistry II (CHM 224)
Slide Lecture 2: January 17
Physical.Proper1es:.Acidity
45
Conjugate bases weaker than phenoxide (whose conjugate acids are stronger than phenol) do not react significantly with phenols.
Keq = 10 -[10 - 6.4] = 10 -[3.6] =10–3.6
Acid-base equilibria always lie to the side with weaker conjugate acids and bases.
© 2013, Dr. Chad L. LandrieOrganic Chemistry II (CHM 224)
Slide Lecture 2: January 17
Physical.Proper1es:.Acidity
46
Acid pKa FormulaConjugate base
(CB)Conjugate base
(CB) Keq
PhOH + CB
hydrogen chloride –3.9 HCl Cl– chloride 10 –13.9
hydronium ion -1.7 H3O+ H2O water 10 –11.7
acetic acid 4.7 CH3COOH CH3COO– acetate 10 –5.3
carbonic acid 6.4 H2CO3 HCO3– bicarbonate 10 –3.6
phenol 10 C6H5OH C6H5O– phenoxide –
methyl ammonium 10.7 CH3NH3+ CH3NH2 methyl amine 10 0.7
water 15.7 H2O OH– hydroxide 10 5.7
ethanol 16 CH3CH2OH CH3CH2O– ethoxide 10 6
acetylene 26 HC≡CH HC≡C– acetylide 10 16
diisopropylamine 36 [(CH3)2CH2]2NH [(CH3)2CH2]2N– diisopropyl amide 10 26
methane 60 CH4 CH3– 10 50
completedeprotonation
PhOH + CB– ➞ PhO– + HCB
© 2013, Dr. Chad L. LandrieOrganic Chemistry II (CHM 224)
Slide Lecture 2: January 17
Aqueous.Extrac1on
47
R
O
O HR
O
OOH+ + H2O
carboxylic acid(conjugate acid)
carboxylate anion(conjugate base)
OOH H2O
phenol(conjugate acid)
phenoxide anion(conjugate base)
O+ +
H2O
amine(conjugate base)
ammonium cation(conjugate acid)
+ +R NH2
H
H OH2
deprotonation
deprotonation
protonationR NH3
R R
When R is small (generally ≤8 carbons; although exceptions) these ions are soluble in water.
© 2013, Dr. Chad L. LandrieOrganic Chemistry II (CHM 224)
Slide Lecture 2: January 17
Separa1on.of.Phenol.from.Mixtures.by.Alkanline,.Aqueous.Extrac1on
48
© 2013, Dr. Chad L. LandrieOrganic Chemistry II (CHM 224)
Slide Lecture 2: January 17
Subs1tuent.Effects.on.Phenol.Acidity
49
1. Alkyl substituents have negligible effects on acidities. When they do, they are slightly electron donating; thus, they may increase the electron density on the phenoxide oxygen and make the phenol less acidic.
p-cresol(pKa = 10.2)
phenol(pKa = 10.0)
© 2013, Dr. Chad L. LandrieOrganic Chemistry II (CHM 224)
Slide Lecture 2: January 17
Subs1tuent.Effects.on.Phenol.Acidity
50
2. Weakly electronwithdrawing substituents have negligible effects on acidities. When they do, they may decrease the electron density on the phenoxide oxygen and make the phenol more acidic.
p-chlorophenol(pKa = 9.4)
phenol(pKa = 10.0)
© 2013, Dr. Chad L. LandrieOrganic Chemistry II (CHM 224)
Slide Lecture 2: January 17
Subs1tuent.Effects.on.Phenol.Acidity
51
3. Nitro substituents have significatnt effects on acidities, particularly at ortho & para positions. They decrease the electron density on the phenoxide oxygen (stabilize the conjugate base) inductively and through resonance and make the phenol more acidic.
o-nitrophenol(pKa = 9.2)
p-nitrophenol(pKa = 9.2)
CHM'224'•'Organic'Chemistry'IISpring'2013,'Des'Plaines'•'Prof.'Chad'Landrie
Reac'ons*of*phenols*(17.9;*Ch.*16)Ethers*and*Epoxides*(18.1M18.4)
Next'Lecture.'.'.
CHM'224'•'Organic'Chemistry'IISpring'2013,'Des'Plaines'•'Prof.'Chad'Landrie
Exp.'33:'ProperHes'and'IdenHficaHon'of'Alcohols
© 2013, Dr. Chad L. LandrieOrganic Chemistry II (CHM 224)
Slide Lecture 2: January 17
Ceric.Ammonium.Nitrate.Test
55
(NH4)2Ce(NO3)6 R-OH (NH4)2Ce(NO3)5
OR+ HNO3+
ceric ammonium nitrate (CAN);
orange
R = alkyl (red)R = aryl (brown)
OHOH
OH
O O
1-butanol phenol diethyl ether butanal 2-butanone
color?
•Based on your results, what class of nucleophilic oxygen atoms form complexes with CAN?•What other functional groups might form similar complexes?
© 2013, Dr. Chad L. LandrieOrganic Chemistry II (CHM 224)
Slide Lecture 2: January 17
Solubility.Tests
56
OH OH OH OH
OH OH
Cl
ethanol 1-butanol 1-hexanol 1-octanol phenol p-chloropehnol
water solubility (s: solubleps: partiallyin: insoluble)
1.0 M NaOH solubility
•Why are some alcohols soluble and some not if all do H-bonding? Use VWFs to explain.•Which insoluble alcohols can be made soluble by NaOH? Why?
© 2013, Dr. Chad L. LandrieOrganic Chemistry II (CHM 224)
Slide Lecture 2: January 17
Jones.Oxida1on.(Chromic.Acid).Test
57
OH OHOH OH OH
1-butanol 1-hexanol 2-butanol cyclohexanol 2-methyl-2-propanol unknown
?
substitution(3º, 2º, 1º)
color change
•Which alcohol(s) did not undergo oxidation? Why?•What is the mechanism for this reaction?
OH
Cr
O
OO+H2SO4 H2O + Cr
O O
HO OH
OCr
O O
OH+
Cr(VI)orange-brown
Cr(II/III)blue-green
© 2013, Dr. Chad L. LandrieOrganic Chemistry II (CHM 224)
Slide Lecture 2: January 17
Lucas.Test
58
OH OHOH OH OH
1-butanol 1-hexanol 2-butanol cyclohexanol 2-methyl-2-propanol unknown
?
substitution(3º, 2º, 1º)
observation
•What is the mechanism for this reaction? What is the intermediate?•Rank the substitution of alcohols in order increasing rate of reaction with Lucas reagent.•Why does the solution become cloudy or form two layers upon reaction?
OH
+ HClZnCl2Cl
homogeneous (one layer) cloudy or two layers
© 2013, Dr. Chad L. LandrieOrganic Chemistry II (CHM 224)
Slide Lecture 2: January 17
Single.Displacement.Redox.of.Alkali.Metals
59
2Na(s) + 2H2O(l) → 2NaOH(s) + H2(g)0 +1 –2 +1 +1–2 0
2Na(s) + CH3OH(l) → 2NaOCH3(s) + H2(g)
•Why is the sodium metal washed with hexanes first?•Why is the sodium metal cut before it’s placed in the alcohol?•What does phenolphthalein indicate? Why should it be added last and not first?
Br CH3ONa+ OCH3
Alkoxides can be formed this way and used in the Williamson Ether Synthesis.