Download Synthesis of 2º Alcohols Grignard + aldehyde yields a secondary alcohol. =>
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Download Download Synthesis of 2º Alcohols Grignard + aldehyde yields a secondary alcohol. =>...
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Synthesis of 2º Alcohols Grignard + aldehyde yields a secondary alcohol. CH3 H3C C CH2
C
H
H
CH3
H3C
H MgBr
C O
CH3
CH CH2
CH3 CH2
H
MgBr
H
CH3 CH3
C O
CH CH2
CH3 CH2
HOH
C O H H
=>
Synthesis of 3º Alcohols Grignard + ketone yields a tertiary alcohol. CH3 H3C C CH2
C
H
H
CH3
H3C
H MgBr
C O
CH3
CH CH2
CH3 CH2
H3C
MgBr
CH3
CH3 CH3
C O
CH CH2
CH3 CH2
HOH
C O H CH3
=>
How would you synthesize… OH
CH2OH
CH3CH2CHCH2CH2CH3
OH
OH
CH3
C CH3 CH2CH3
=>
Grignard Reactions with Acid Chlorides and Esters • Use two moles of Grignard reagent. • The product is a tertiary alcohol with two identical alkyl groups. • Reaction with one mole of Grignard reagent produces a ketone intermediate, which reacts with the second mole of Grignard reagent. =>
Grignard + Acid Chloride (1) • Grignard attacks the carbonyl. • Chloride ion leaves. CH3
H3C R
MgBr
C O Cl
CH3 R C O Cl
R C O
MgBr
Cl CH3
MgBr
R C
+
MgBrCl
O
Ketone intermediate
=>
Grignard and Ester (1) • Grignard attacks the carbonyl. • Alkoxide ion leaves! ? ! CH3
H3C R
MgBr
C O CH3O
CH3 R C O OCH3
R C O
MgBr
OCH3 CH3
MgBr
R C
+ O
MgBrOCH3
Ketone intermediate
=>
Second step of reaction • Second mole of Grignard reacts with the ketone intermediate to form an alkoxide ion. • Alkoxide ion is protonated with dilute acid. CH3
CH3 R
MgBr
+
R C
R C O O
MgBr
R
HOH CH3 R C OH R
=>
How would you synthesize... Using an acid chloride or ester.
OH
CH3
CH3CH2CCH3
C
CH3
OH
OH CH3CH2CHCH2CH3
=>
Grignard Reagent + Ethylene Oxide • Epoxides are unusually reactive ethers. • Product is a 1º alcohol with 2 additional carbons. O
O MgBr
+
CH2
CH2CH2
CH2
HOH O H CH2CH2
=>
MgBr
Limitations of Grignard • No water or other acidic protons like O-H, N-H, S-H, or -C—C-H. Grignard reagent is destroyed, becomes an alkane. • No other electrophilic multiple bonds, like C=N, C—N, S=O, or N=O. =>
Reduction of Carbonyl • Reduction of aldehyde yields 1º alcohol. • Reduction of ketone yields 2º alcohol. • Reagents: – Sodium borohydride, NaBH4 – Lithium aluminum hydride, LiAlH4 – Raney nickel
=>
Sodium Borohydride • Hydride ion, H , attacks the carbonyl carbon, forming an alkoxide ion. • Then the alkoxide ion is protonated by dilute acid. • Only reacts with carbonyl of aldehyde or ketone, not with carbonyls of esters or carboxylic acids. O C H
H
H C
H
O +
H
H3O
O H
C
H
=>
Lithium Aluminum Hydride • Stronger reducing agent than sodium borohydride, but dangerous to work with. • Converts esters and acids to 1º alcohols. O C
OCH3
H LAH
H3O+
C
O H H
=>
Comparison of Reducing Agents • LiAlH4 is stronger. • LiAlH4 reduces more stable compounds which are resistant to reduction. =>
Catalytic Hydrogenation • Add H2 with Raney nickel catalyst. • Also reduces any C=C bonds. OH
O
NaBH4
OH H2, Raney Ni
=>
Thiols (Mercaptans) • • • • •
Sulfur analogues of alcohols, -SH. Named by adding -thiol to alkane name. The -SH group is called mercapto. Complex with heavy metals: Hg, As, Au. More acidic than alcohols, react with NaOH to form thiolate ion. Stinks! => •
Thiol Synthesis Use a large excess of sodium hydrosulfide with unhindered alkyl halide to prevent dialkylation to R-S-R. _ H S
_ R X
R
SH
+ X
=>
Thiol Oxidation • Easily oxidized to disulfides, an important feature of protein structure. Br2 R
SH
+ HS
R
R
S
S
R +
2 HBr
Zn, HCl
Vigorous oxidation with KMnO4, HNO3, or NaOCl, produces sulfonic acids. •
SH
HNO3 boil
O S O
OH
=>
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