Dr.

Manashi Chatterjee Recitation-Week-1-KEY

Chem 224

Review:
Addition reaction of Alkene (hydration, oxidation, reduction)
and Alkynes (selective reduction to alkenes)
Synthesis of Alkenes: E-1 (Dehydration of alcohols) and E-2 (Base catalyzed elimination
of alkyl halides or tosylates) and Reduction of alkynes
Synthesis of Alkynes: SN2 (using salts of alkynes and primary alkyl halides or tosylates);
double elimination of dihalides
Synthesis of salts of Alkynes and Alcohols (alkoxides): using appropriate bases (acid-
base reaction concepts); Understanding salts of alkynes and alkoxides can act as
nucleophile or bases and under go SN2 or E-2 depending on nature of leaving group
and solvent
Use of bulky alkoxides for Elimination: Hoffman product
Epoxide opening: with strong nucleophiles
Substitution reactions (SN2 and SN1)
Synthesis of alkyl halides: Radical reactions: using Br2/ light and NBS / light
OR addition of HBr to alkenes
OR Using Alcohols and HBr or PBr3 or SOCl2
Synthesis of Ethers: Using SN2 using primary alkyl halide and non bulky alkoxide OR
addition of alcohols to alkenes (acid catalyzed or Hg salt catalyzed)
Synthesis of epoxides, aldehydes, ketones, acids, diols by oxidation of alkenes and
alkynes

1. Provide the missing Reagents (Carbene reactions were not covered)

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Dr. Manashi Chatterjee Recitation-Week-1-KEY
Chem 224

Answer is E

Give the correct order of reagents

Br
OH

1) MCPBA
A. 2) H3O+ E. Br2 I. NaOMe

B. OsO4 (catalytic), NMO F. H2/Pt J. HBr

1) Hg(OAc)2, H2O
C. 2) NaBH4 G. Br2/H2O K. TsCl/pyridine

1) BH3.THF
D. 2) H2O2, NaOH
H. L. HBr/H2O2
O-

Answer is H and then C

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Dr. Manashi Chatterjee Recitation-Week-1-KEY
Chem 224

3. Provide the missing reagents

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Dr. Manashi Chatterjee Recitation-Week-1-KEY
Chem 224

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Dr. Manashi Chatterjee Recitation-Week-1-KEY
Chem 224

4. Provide the missing Reagents

5. Show how to synthesize (Z)-3-heptene from acetylene as one of the starting

material

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Dr. Manashi Chatterjee Recitation-Week-1-KEY
Chem 224

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Dr. Manashi Chatterjee Recitation-Week-1-KEY
Chem 224

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Dr. Manashi Chatterjee Recitation-Week-1-KEY
Chem 224

Summary of important reagents and reactions:

I: To add Br (make alkyl halides)

a. Alkene and Br2/CCl4 (adds 2 Br; anti addition): Trans symmetric alkene: check for
Meso
b. Alkene and Br2/H2O (adds Br and OH; anti addition)
c. Alkene and HBr (adds one Br, migration and rearrangement possible; Markovnikov
addition)
d. Alkene and HBr in presence of peroxides and light or heat (Anti-Markovnikov
addition)
e. Alkyne and HBr (2 equivalents): Both Br goes to the same Carbon
f. Alkene and NBS in presence of peroxides and light or heat (Allylic bromination)
h. Alkane and Br2 and light or heat
(Note benzene ring is not alkene)
i. tertiary alcohol and HBr/HCl

II: To make alcohols

a. Alkene+ H2O/H2SO4 (not good for tertiary alcohols, also rearrangement possible;
Markovnikov addition)
b. Alkene+ Hg(OAc)2;H2O followed by NaBH4 (Markovnikov addition; no migration)
c. Alkene+BH3.THF followed by H2O2/NaOH (Anti-Markovnikov addition)
d. Alkyl halide and Base to alkene and then the above reactions
e. primary alkyl halides and NaOH
f. Anions of terminal alkynes opening epoxides and carbonyl
g. Alkyne can be selectively reduced to alkene and the hydration (one of the 3 hydrations)

III: To make aldehydes and ketones and acids

a. Alkene can be cleaved by O3 / (CH3)2S to aldehydes and Ketone (reducing condition)
b. Alkenes to cis diols and cleavage by HIO4 or cold KMnO4 to aldehyes and ketones
c. Alkene to diols and Warm KMnO4 to acids
d. Alkynes and warm KMnO4 give acids
e. Pinacol reactions (diols and conc acids)

These are also methods but we have not covered them

a. primary Alcohol and PCC/CH2Cl2: Aldehyde (Oxidation)
b. primary alcohol and Jones (H2CrO4) or KMnO4: Acids
c. secondary alcohol and Jones or PCC: Ketone
d. tertiary alcohol: no reaction
e. Alkynes hydration with H2SO4/HgSO4; provides methyl ketones or other ketones
f. Terminal Alkynes hydration with (sia)2BH, H2O2/NaOH: Aldehydes

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Dr. Manashi Chatterjee Recitation-Week-1-KEY
Chem 224

IV. Bases for deprotonating terminal alkynes (method to increase carbon chain)
NaH, NaNH2, BuLi, LDA (can not use NaOH, NaOEt or tert-BuO K; NH3 or Et3N;
NaHCO3 or Na2CO3)
check the pka of alkyne and the conjugate acid that is formed

V. Hydrogenation reagents
a. Alkene /Alkyne to alkane (H2; Pd/Ni)
b. Alkyne to Cis alkene (Lindlar, H2) (alkenes can then be converted to alcohols and
carbonyl compounds)
c. Alkyne to trans alkene (Na/ liquid NH3) (alkenes can then be converted to alcohols and
carbonyl compounds)

VI. Epoxide forming reactions and reactions of epoxides

a. RCO3H; peroxy acids
b. Alkene with Br2/H2O; followed by base (NaOH)
(epoxides can be opened with strong nucleophiles (amines, OH-, OR-) at less hindered
site SN2; and with weak nucleophiles in presence of acids)

VII. Diol formation

a. Alkene+OsO4 followed by NaHSO3
b. Opening of epoxides with bases (NaOH); trans diols

VII. Formation of alkoxides (RO-) or (PhO-)

a. Alcohol+ Na metal or K metal
b. Alcohol+ NaH or NaNH2 or BuLi or LDA
(can not use NaOH, NaOEt or tert-BuO K; NH3 or Et3N; NaHCO3 or Na2CO3)

-
NaOH, NaOEt or tert-BuOK can deprotonate PhOH (phenols) to make PhO (phenoxide)
-
ond RSH (thiols) RS

Ether forming reactions

a. Williamsons synthesis: Primary alkyl halide and alkoxides (Alkoxides are also bases so
sec and tert alkyl halides will give major elimination product)
b. Alkene and H2SO4/alcohol or Alkene and Hg(OAc)2 / ROH followed by NaBH4

Alkene formation

a. Primary Alkyl halide and Bases (tert-BuO-Na+, bulky base; other bases (NaOEt,
NaOMe will form ethers )
b. Sec and tert alkyl halides+ NaOEt or tert-BuO-Na+

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Chem 224

c. Alcohol dehydration (H2SO4/H2O or H3PO4/H2SO4)

d. Alcohols convered to alkylsulfonates or Mesylates or alkyl halides (with HX)and
treated with base

Nucleophilic substitution reactions:

a. Alkyl halides and Nu (weak or strong)
b. Alkyl sulfonates (ROTs/ROMs) with Nucleophiles

Nucleophiles (Substitution reactions)

Strong: NaCN, NaOAc, NaN3, NaSH, NaSCH3, acetylide ions (terminal alkyne and
strong base),
Amines (primary and sec)
Weak: H2O, CH3OH, CH3SH, CH3COOH

(NaOCH3, NaOPh, NaOEt, acetylide ions) act as nucleophile only when leaving group is
on primary carbon. If leaving group is on secondary or tertiary these will act as bases ,
pick the beta hydrogen and give alkenes

Bases: Conjugate acids have a pKa > 15

Tertiary amines: Et3N, Pyridine (used in acid base reaction)

Strong bases: NaH, NaNH2, BuLi (not used as nucleophiles with halides and Tosylates)
tert-BuO-Na+ is used to convert alkyl halides or Tosylates to alkenes
NaOEt and NaOCH3 (in alcohol solvent and heat) is used to convert sec and tert alkyl
halides or tosylates to alkenes
Very mild base: NaHCO3 (sodium bicarbonate; conjugate acid is H2CO3: pKa= 6.6) can
react with carboxylic acids (pKa= 4) but not with phenols (pKa=9) or alcohols or RSH
For acid base reactions equilibrium moves towards direction of weak acid (higher pKa)

To add Carbons:

1. Think epoxides opening with CN or salt of alkyne

2. CN can add one Carbon to R-X or R-OTs
4. Anions of terminal Alkynes reacting primary alkyl halides or open epoxides

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