Chemistry 125: Lecture 67April 12, 2010

Oxidizing/Reducing AlcoholsGrignard ReactionsGreen Chemistry

This

For copyright notice see final page of this file

(Loudon)

Alcohol Oxidation (sec. 16.14)

Stopping at Aldehyde (p. 805-6)

Vicinal Diol Cleavage by IO4- (sec. 16.14b)

Pyridinium Chlorochromate (Cl-CrO2O-)

“In practice the chromium byproduct deposits with pyridine as a sticky black tar, which can complicate matters.” (Wikipedia)

no water; no diol; no

overoxidation

0:49-11:35

Good Practice to Fill in Reagents

Alcohol (retro)Synthesis(secs. 16.13, 16.15)

Hydride Reduction (sec. 16.13 p. 802)

O

“Versatility” of Grignard Reagent

R-OH R-Br R-MgBrPBr3 Mg

O

CH2

O

CH

O

C

Is there a preferred order?

O

C

nucleophiliccarbon?

from alkene

(3 steps from CH3OH)

or

(1 step from CH3OH)

“Versatility” of Grignard Reagent

1) CH3MgBrO

OH

CH3

95%

2) H+ / H2O MgBr

OH

t-Bu

0%

1) t-BuMgBr

2) H+ / H2OO

1) t-BuCH2MgBr

2) H+ / H2OO

OH

CH2-t-Bu

4%

OMgBrH

H

OH

65%

H- reduction

H-CH2-t-Bu

H

H-t-Bu+ ketone

35%

H+

+ enolate ketone90%

from Roberts & Caserio (1965)

Cf. 2 t-Bu t-Bu-H

+

no H

avoid steric hindrance

H

:-(

+

“Versatility” of Grignard Reagent

from Roberts & Caserio (1965)

Risk of Reduction

H

and steric

hindrance

Wittig Reaction (sec. 16.17)

Ph3P is good at taking up O to form strong Ph3P=O bond.

Biological Oxidation

NAD+ , NADH revisited (sec. 16.18)

“Lithium aluminum hydride, having a molecular weight of 38 and four hydrides per molecule, has the highest hydride density and is frequently

used, even though it cogenerates an inorganic by-product which is difficult to separate from the product…slow filtration and product loss

through occclusion or adsorption are typical problems…”

Pharmaceuticals generate < 0.2% of the chemical industry’s product mass, but some 25% of its $ value,

and >50% of its chemical waste.

Table 1 Reactions companies use now but would strongly prefer better reagents

Amide formation avoiding poor atom economy reagents 6 votes

OH activation for nucleophilic substitution 5 votes

Reduction of amides without hydride reagents 4 votes

Oxidation/Epoxidation methods without the use of chlorinated solvents 4 votes

Safer and more environmentally friendly Mitsunobu reactions 3 votes

Friedel-Crafts reaction on unactivated systems 2 votes

Nitrations 2 votes

“Key green chemistry research areas - a perspective from pharmaceutical manufacturers” Green Chemistry, 2007, 9, 411-420

Pharmaceuticals generate < 0.2% of the chemical industry’s product mass, but some 25% of its $ value,

and >50% of its chemical waste.

Research AreaNumber of roundtable companies voting for this research area as a priority area

“…the use of stoichiometric high-valent metals (Mn, Os, Cr) have virtually been eliminated

from pharmaceutical processes…”

End of Lecture 67April 12, 2010

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