Table Of ContentOxidation of Primary Alcohols
to Carboxylic Acids
BASIC REACTIONS IN ORGANIC SYNTHESIS
EDITOR-IN-CHIEF:GABRIELTOJO
DEPARTMENTOFORGANICCHEMISTRY
FACULTYOFCHEMISTRY
UNIVERSITYOFSANTIAGODECOMPOSTELA
15872-SANTIAGODECOMPOSTELASPAIN
[email protected]
OxidationofAlcoholstoAldehydesandKetones:
AGuidetoCurrentCommonPractice,byGabrielTojoandMarcosFernández
OxidationofPrimaryAlcoholstoCarboxylicAcids:
AGuidetoCurrentCommonPractice,byGabrielTojoandMarcosFernández
Oxidation of Primary
Alcohols to Carboxylic
Acids
A Guide to Current Common Practice
GABRIEL TOJO and MARCOS FERNÁNDEZ
Authors:
GabrielTojo MarcosFernández
DepartmentofOrganicChemistry DepartmentofOrganicChemistry
FacultyofChemistry FacultyofChemistry
UniversityofSantiagodeCompostela UniversityofSantiagodeCompostela
15872-SantiagodeCompostela 15872-SantiagodeCompostela
Spain Spain
Editor-in-Chief
GabrielTojo
DepartmentofOrganicChemistry
FacultyofChemistry
UniversityofSantiagodeCompostela
15872-SantiagodeCompostela
Spain
LibraryofCongressControlNumber:2006929452
ISBN-10:0-387-35431-X
ISBN-13:978-0387-35431-6
e-ISBN-10:0-387-35432-8
e-ISBN-13:978-0387-35432-3
Printedonacid-freepaper.
©2007SpringerScience+BusinessMedia,LLC
Allrightsreserved.Thisworkmaynotbetranslatedorcopiedinwholeorinpartwithoutthewritten
permissionofthepublisher(SpringerScience+BusinessMedia,LLC,233SpringStreet,NewYork,
NY10013,USA),exceptforbriefexcerptsinconnectionwithreviewsorscholarlyanalysis.Usein
connection with any form of information storage and retrieval, electronic adaptation, computer
software,orbysimilarordissimilarmethodologynowknownorhereafterdevelopedisforbidden.
The use in this publication of trade names, trademarks, service marks and similar terms, even if
theyarenotidentifiedassuch,isnottobetakenasanexpressionofopinionastowhetherornot
theyaresubjecttoproprietaryrights.
10987654321
springer.com
This book is dedicated to the thousands of scientists cited in the
references who constructed our present knowledge on the
oxidation of primary alcohols to carboxylic acids. Thanks
to their collective effort, the preparation of medicines,
pesticides, colorants, and a variety of chemicals that make life
more enjoyable, is greatly facilitated.
Preface to the Series
Thereisnaturalselectioninthesyntheticorganiclaboratory.Successfulreagents
findtheirwayintospecializedjournalsandtendtopopulateresearchers’benches.
Sometimes, old species—like active manganese dioxide in the oxidation of
unsaturated alcohols—are so well adapted to a certain reaction niche that they
remain unchallenged for a long time. On other occasions, a successful new
species—likeDessMartinperiodinane—enjoysapopulationexplosionandvery
quicklyinhabitsagreatnumberoflaboratories.Ontheotherhand,theliterature
isfilledwithpromisingnewreagentsthatfellintooblivionbecausenobodywas
able to replicate the initial results on more challenging substrates.
Thisseries,whichconsistsofacollectionofmonographsonbasicreactions
in organic synthesis, is not primarily aimed at specialized researchers interested
in the development of new reagents. Rather, it is written with the objective of
beingapracticalguideforanykindofscientist,beitachemistofwhateversort,
a pharmacologist, a biochemist, or whoever has the practical need to perform a
certainbasicsyntheticoperationinthequickestandmostreliableway.Therefore,
great emphasis is given to those reagents that are employed most often in
laboratories,becausetheirubiquityprovesthattheypossessagreaterreliability.
Reagentsappearinginonlyafewpublications,regardlessofpromisingpotential,
are only briefly mentioned. We prefer to err on the side of ignoring some good
reagents, rather than including bad reagents that would lead researchers to lose
precious time.
Thebooksfromthisseriesaremeanttobeplacednearworkingbenchesin
laboratories,ratherthanontheshelvesoflibraries.Thatiswhyfullexperimental
details for important reactions are provided. Although many of references from
the literature are facilitated, this series is written with the aim of avoiding as
muchaspossibletheneedtoconsultoriginalresearcharticles.Manyresearchers
do not have scientific libraries possessing numerous chemical journals readily
available, and, many times, although such libraries might be on hand, it is
inconvenient to leave the laboratory in order to consult some reference.
Our aim is to facilitate practical help for anybody preparing new organic
compounds.
vii
Preface
There is a common view among organic chemists that simple functional group
transformations are a mature technology away from the forefront in the Art
of Organic Synthesis. This is undoubtedly not the case in the conversion of
primaryalcoholsintocarboxylicacids.Anidealreagentforsuchtransformation
should be (1) reliable and efficient with regard to all molecules, including
complex structures possessing oxidation-sensitive functional groups, (2) cheap,
and (3) environmentally friendly. There is no such reagent, even if we limit
ourselvestothemoremundaneneedofanythingabletoprovideacertainmuch-
needed carboxylic acid, regardless of price and ecology. This state of affairs is
highlighted by the fact that in forty percent of cases the oxidation of primary
alcoholstoacidsisperformedusingatwo-stepprocedureviathecorresponding
aldehydes;somethingthatprovesthattheoxidationofalcoholstoaldehydesisa
muchmorematuretechnologythantheoxidationofalcoholstocarboxylicacids.
This monograph is a laboratory guide for the transformation of primary
alcohols into carboxylic acids. It displays a panorama of the state of the art
for this functional group transformation, highlighting the weaponry currently
availableforscientistsandareaswherefurtherprogressisneeded.Inconformity
with the rest of the series, a selection is made to include those procedures that
have proved more reliable in many laboratories around the globe.
ix
Abbreviations
Ac acetyl Me methyl
Alloc allyloxycarbonyl MEM (2-methoxyethoxy)methyl
BAIB bis(acetoxy)iodobenzene min. minute
Bn benzyl MOM methoxymethyl
Boc t-butoxycarbonyl MS molecular sieves
b.p. boiling point MTBE methyl t-butyl ether
Bu n-butyl MW molecular weight
t-Bu tert-butyl NCS N-chlorosuccinimide
Bz benzoyl NMO N-methylmorpholine
ca. circa N-oxide
CA Chemical Abstracts NMR nuclear magnetic
cat. catalytic resonance
Cbz benzyloxycarbonyl PCC pyridinium
DCAA dichloroacetic acid chlorochromate
DCC N(cid:2)N(cid:2)-dicyclohexyl PDC pyridinium dichromate
carbodiimide Ph phenyl
DMF dimethylformamide PhF 9-phenylfluorenyl
DMP Dess-Martin periodinane Pht phthaloyl
DMSO dimethyl sulfoxide PMB p-methoxybenzyl
ee enantiomeric excess ppm parts per million
EE 1-ethoxyethyl Pr propyl
eq. equivalent Py pyridine
Et ethyl ref. reflux
Fmoc 9-fluorenyl r.t. room temperature
methoxycarbonyl sat. saturated
g gram T temperature
h hour TBDPS t-butyldiphenylsilyl
i-Pr isopropyl TBS t-butyldimethylsilyl
L liter TEMPO 2,2,6,6-tetramethyl-
m multiplet 1-piperidinyloxy free
M mol/L radical
MCPBA m-chloroperoxybenzoic TFA trifluoroacetic acid
acid TFAA trifluoroacetic anhydride
xi
xii Abbreviations
THF tetrahydrofuran TPAP tetrapropylammonium
THP tetrahydropyran-2-yl perruthenate
T internal temperature v volume
i
TIPS triisopropylsilyl w weight
TMS trimethylsilyl Z benzyloxycarbonyl
Contents
1. Permanganate..................................................... 1
1.1.Introduction.................................................... 1
1.2.General Procedure for Oxidation of Primary Alcohols to Carboxylic
Acids with Potassium Permanganate ............................. 5
1.3.Functional Group and Protecting Group Sensitivity to Potassium
Permanganate.................................................. 7
1.4.Side Reactions................................................. 9
1.5.References..................................................... 10
2. Jones and Other CrO -Based Oxidations........................... 13
3
2.1.Introduction.................................................... 13
Mechanism..................................................... 13
Inverse Addition................................................ 15
Solvent........................................................ 16
Acidity........................................................ 17
Zhao’s Catalytic CrO Oxidation................................. 18
3
2.2.General Procedure for Oxidation of Primary Alcohols
to Carboxylic Acids with Jones Reagent.......................... 19
2.3.Functional Group and Protecting Group Sensitivity to Jones
Oxidation...................................................... 21
2.4.Side Reactions................................................. 25
2.5.References..................................................... 28
3. Pyridinium Dichromate (PDC) in Dimethylformamide.
The Method of Corey and Schmidt................................. 33
3.1.Introduction.................................................... 33
3.2.General Procedure for Oxidation of Aliphatic Primary Alcohols to
Carboxylic Acids with Pyridinium Dichromate
in Dimethylformamide. Method of Corey and Schmidt............. 34
3.3.Functional Group and Protecting Group Sensitivity to PDC in DMF 36
3.4.Side Reactions................................................. 38
3.5.References..................................................... 39
xiii
