Pirkle's alcohol
Encyclopedia
Pirkle's alcohol is an off-white, crystalline solid that is stable at room temperature when protected from light and oxygen. This chiral
molecule is typically used, in nonracemic form, as a chiral shift reagent in nuclear magnetic resonance spectroscopy, in order to simultaneously determine absolute configuration
and enantiomeric purity of other chiral molecules. The molecule is named after William H. Pirkle, Professor of Chemistry at the University of Illinois whose group reported its synthesis and its application as a chiral shift reagent.
, to yield trifluoromethyl 9-anthryl ketone
. Trifluoromethyl 9-anthryl ketone may be reduced with a chiral hydride reagent prepared from lithium aluminium hydride
and (4S,5S)-(–)-2-ethyl-4-hydroxymethyl-5-phenyl-2-oxazoline to generate Pirkle’s alcohol with R absolute configuration. Alternatively, trifluoromethyl 9-anthryl ketone may be reduced with sodium borohydride
to generate racemic Pirkle’s alcohol. The enantiomers are then derivatized to diastereomeric carbamate
s using enantioenriched 1-(1-Naphthyl)ethyl isocyanate
(also developed by Pirkle). These diastereomers may be separated by column chromatography
and hydrolyzed to obtain each enantiomer of Pirkle’s alcohol in enantiopure form.
. Pirkle’s alcohol is applied to obtain this information by NMR spectroscopy
. When Pirkle’s alcohol is in solution with an ensemble of chiral molecules, short-lived diastereomeric solvates may be formed from Pirkle’s alcohol and the enantiomers of the analyte. Enantiomorphic protons of the analyte enantiomers, which without Pirkle’s alcohol are indistinguishable by NMR, become diastereomorphic when the analyte interacts with Pirkle’s alcohol, and appear as different signals in an NMR spectrum. The relative magnitude of the signals quantitatively reveals the enantiomeric purity of the analyte. Also, a model of the solvated complex may be used to deduce absolute configuration of an enantioenriched analyte.
Chirality (chemistry)
A chiral molecule is a type of molecule that lacks an internal plane of symmetry and thus has a non-superimposable mirror image. The feature that is most often the cause of chirality in molecules is the presence of an asymmetric carbon atom....
molecule is typically used, in nonracemic form, as a chiral shift reagent in nuclear magnetic resonance spectroscopy, in order to simultaneously determine absolute configuration
Absolute configuration
An absolute configuration in stereochemistry is the spatial arrangement of the atoms of a chiral molecular entity and its stereochemical description e.g. R or S....
and enantiomeric purity of other chiral molecules. The molecule is named after William H. Pirkle, Professor of Chemistry at the University of Illinois whose group reported its synthesis and its application as a chiral shift reagent.
Synthesis
Pirkle’s alcohol is synthesized by trifluoroacetylation of anthraceneAnthracene
Anthracene is a solid polycyclic aromatic hydrocarbon consisting of three fused benzene rings. It is a component of coal-tar. Anthracene is used in the production of the red dye alizarin and other dyes...
, to yield trifluoromethyl 9-anthryl ketone
Ketone
In organic chemistry, a ketone is an organic compound with the structure RCR', where R and R' can be a variety of atoms and groups of atoms. It features a carbonyl group bonded to two other carbon atoms. Many ketones are known and many are of great importance in industry and in biology...
. Trifluoromethyl 9-anthryl ketone may be reduced with a chiral hydride reagent prepared from lithium aluminium hydride
Lithium aluminium hydride
Lithium aluminium hydride, commonly abbreviated to LAH or known as LithAl, is an inorganic compound with the chemical formula LiAlH4. It was discovered by Finholt, Bond and Schlesinger in 1947. This compound is used as a reducing agent in organic synthesis, especially for the reduction of esters,...
and (4S,5S)-(–)-2-ethyl-4-hydroxymethyl-5-phenyl-2-oxazoline to generate Pirkle’s alcohol with R absolute configuration. Alternatively, trifluoromethyl 9-anthryl ketone may be reduced with sodium borohydride
Sodium borohydride
Sodium borohydride, also known as sodium tetrahydridoborate, is an inorganic compound with the formula NaBH4. This white solid, usually encountered as a powder, is a versatile reducing agent that finds wide application in chemistry, both in the laboratory and on a technical scale. Large amounts are...
to generate racemic Pirkle’s alcohol. The enantiomers are then derivatized to diastereomeric carbamate
Carbamate
Carbamates are organic compounds derived from carbamic acid . A carbamate group, carbamate ester, and carbamic acids are functional groups that are inter-related structurally and often are interconverted chemically. Carbamate esters are also called urethanes.-Synthesis:Carbamic acids are derived...
s using enantioenriched 1-(1-Naphthyl)ethyl isocyanate
Isocyanate
Isocyanate is the functional group of elements –N=C=O , not to be confused with the cyanate functional group which is arranged as –O–C≡N or with isocyanide, R-N≡C. Any organic compound which contains an isocyanate group may also be referred to in brief as an isocyanate. An isocyanate may have more...
(also developed by Pirkle). These diastereomers may be separated by column chromatography
Column chromatography
Column chromatography in chemistry is a method used to purify individual chemical compounds from mixtures of compounds. It is often used for preparative applications on scales from micrograms up to kilograms.The main advantage of column chromatography is the relatively low cost and disposability...
and hydrolyzed to obtain each enantiomer of Pirkle’s alcohol in enantiopure form.
Application
The determination of enantiomeric purity and absolute configuration is frequently necessary in organic synthesisOrganic synthesis
Organic synthesis is a special branch of chemical synthesis and is concerned with the construction of organic compounds via organic reactions. Organic molecules can often contain a higher level of complexity compared to purely inorganic compounds, so the synthesis of organic compounds has...
. Pirkle’s alcohol is applied to obtain this information by NMR spectroscopy
NMR spectroscopy
Nuclear magnetic resonance spectroscopy, most commonly known as NMR spectroscopy, is a research technique that exploits the magnetic properties of certain atomic nuclei to determine physical and chemical properties of atoms or the molecules in which they are contained...
. When Pirkle’s alcohol is in solution with an ensemble of chiral molecules, short-lived diastereomeric solvates may be formed from Pirkle’s alcohol and the enantiomers of the analyte. Enantiomorphic protons of the analyte enantiomers, which without Pirkle’s alcohol are indistinguishable by NMR, become diastereomorphic when the analyte interacts with Pirkle’s alcohol, and appear as different signals in an NMR spectrum. The relative magnitude of the signals quantitatively reveals the enantiomeric purity of the analyte. Also, a model of the solvated complex may be used to deduce absolute configuration of an enantioenriched analyte.