Mosher acid

Structural formula
	( R ) -Mosher acid (left) and ( S ) -Mosher acid (right)
General
Surname	Mosher acid
other names	3,3,3-trifluoro-2-methoxy-2-phenylpropanoic acid ( IUPAC ); MTPA; α-methoxy-α-trifluoromethylphenylacetic acid;
Molecular formula	C 10 H 9 F 3 O 3
External identifiers / databases
EC number	625-074-7
ECHA InfoCard	100.153.604
PubChem	86531
ChemSpider	78043
Wikidata	Q408407
properties
Molar mass	234.17 g mol −1
density	1.303 g cm −3
Melting point	40-45 ° C ( racemate ) ; 46–49 ° C [( R ) -form or ( S ) -form] ;
boiling point	95-97 ° C (0.05 mmHg)
safety instructions
GHS labeling of hazardous substances Caution
H and P phrases	H: 315-319-335
	P: 261-305 + 351 + 338
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

The Mosher acid (abbreviated as MTPA from the English α-methoxy-α-trifluoromethylphenylacetic acid) is a chiral carboxylic acid that was introduced by Harry S. Mosher (1915-2001) to convert chiral compounds such as alcohols or amines into the corresponding diastereomeric esters or to convert amides . Both enantiomers [the ( S ) or the ( R ) form] of the chiral Mosher acid can be used for this purpose. Because of its much higher reactivity, acid chloride is also often used.

application

The enantiomerically pure Mosher acid is used as a chiral derivatizing reagent of alcohols or amines in order to convert a chiral compound into a diastereomer. The implementation of the reaction of racemic amphetamine with enantiomerically pure ( R ) -Mosher acid is shown schematically. While the enantiomers ( R ) - and ( S ) -amphetamine show identical NMR spectra, the diastereomers ( RS ) and ( RR ) differ from one another in the NMR.

Depending on the response, shifts of up to 47 Hertz are possible.

With the help of the diastereomers, the enantiomeric excess of a stereospecific reaction can be determined or the absolute stereochemistry of a product can be determined. ¹ H and ¹⁹ F NMR spectroscopy are used to determine the absolute configuration .

Individual evidence

↑ ^a ^b ^c Data sheet (S) - (-) - α-Methoxy-α- (trifluoromethyl) phenylacetic acid, ≥99% from Sigma-Aldrich , accessed on December 1, 2019 ( PDF ).
↑ ^a ^b ^c data sheet (±) -α-Methoxy-α-trifluoromethylphenylacetic acid, for GC derivatization, LiChropur at Sigma-Aldrich , accessed on December 1, 2019 ( PDF ).
↑ JA Dale, DL Dull, HS Mosher: α-Methoxy-α-trifluoromethylphenylacetic acid, a versatile reagent for the determination of enantiomeric composition of alcohols and amines. In: Journal of Organic Chemistry 1969 , 34 , pp. 2543-2549 doi : 10.1021 / jo01261a013 .
↑ JA Dale, HS Mosher: Nuclear magnetic resonance enantiomer regents. Configurational correlations via nuclear magnetic resonance chemical shifts of diastereomeric mandelate, O-methylmandelate, and α-methoxy-α-trifluoromethylphenylacetate (MTPA) esters. In: Journal of the American Chemical Society 1973 , 95 , pp. 512-519 doi : 10.1021 / ja00783a034 .
^ Y. Goldberg, H. Alper: A new and simple synthesis of Mosher's acid. In: Journal of Organic Chemistry 1992 , 57 , pp. 3731-3732 doi : 10.1021 / jo00039a043 .
↑ DL Dull, HS Mosher: Aberrant rotatory dispersion curves of α-hydroxy- and α-methoxy-α-trifluoromethylphenylacetic acids. In: Journal of the American Chemical Society 1967 , 89 , pp. 4230-4230 doi : 10.1021 / ja00992a053 .
^ DE Ward, CK Rhee: A simple method for the microscale preparation of Mosher's acid chloride. In: Tetrahedron Letters 1991 , 32 , pp. 7165-7166 doi : 10.1016 / 0040-4039 (91) 80466-J .
↑ D. Parker: NMR determination of enantiomeric purity . In: Chem Rev.. . 91, No. 7, 1991, pp. 1441-1457. doi : 10.1021 / cr00007a009 .
↑ Allen, Damian A .; Tomaso, Anthony E., Jr .; Priest, Owen P .; Hindson, David F .; Hurlburt, Jamie L .: Mosher Amides: Determining the Absolute Stereochemistry of Optically-Active Amines. In: J. Chem. Educ. 2008 , 85 , p. 698. doi : 10.1021 / ed085p698 .

[aldrich-s-1] Data sheet (S) - (-) - α-Methoxy-α- (trifluoromethyl) phenylacetic acid, ≥99% from Sigma-Aldrich , accessed on December 1, 2019 ( PDF ).

[aldrich-rac-2] ta sheet (±) -α-Methoxy-α-trifluoromethylphenylacetic acid, for GC derivatization, LiChropur at Sigma-Aldrich , accessed on December 1, 2019 ( PDF ).

[3] JA Dale, DL Dull, HS Mosher: α-Methoxy-α-trifluoromethylphenylacetic acid, a versatile reagent for the determination of enantiomeric composition of alcohols and amines. In: Journal of Organic Chemistry 1969 , 34 , pp. 2543-2549 doi : 10.1021 / jo01261a013 .

[4] JA Dale, HS Mosher: Nuclear magnetic resonance enantiomer regents. Configurational correlations via nuclear magnetic resonance chemical shifts of diastereomeric mandelate, O-methylmandelate, and α-methoxy-α-trifluoromethylphenylacetate (MTPA) esters. In: Journal of the American Chemical Society 1973 , 95 , pp. 512-519 doi : 10.1021 / ja00783a034 .

[5] Y. Goldberg, H. Alper: A new and simple synthesis of Mosher's acid. In: Journal of Organic Chemistry 1992 , 57 , pp. 3731-3732 doi : 10.1021 / jo00039a043 .

[6] DL Dull, HS Mosher: Aberrant rotatory dispersion curves of α-hydroxy- and α-methoxy-α-trifluoromethylphenylacetic acids. In: Journal of the American Chemical Society 1967 , 89 , pp. 4230-4230 doi : 10.1021 / ja00992a053 .

[7] DE Ward, CK Rhee: A simple method for the microscale preparation of Mosher's acid chloride. In: Tetrahedron Letters 1991 , 32 , pp. 7165-7166 doi : 10.1016 / 0040-4039 (91) 80466-J .

[8] D. Parker: NMR determination of enantiomeric purity . In: Chem Rev.. . 91, No. 7, 1991, pp. 1441-1457. doi : 10.1021 / cr00007a009 .

[9] Allen, Damian A .; Tomaso, Anthony E., Jr .; Priest, Owen P .; Hindson, David F .; Hurlburt, Jamie L .: Mosher Amides: Determining the Absolute Stereochemistry of Optically-Active Amines. In: J. Chem. Educ. 2008 , 85 , p. 698. doi : 10.1021 / ed085p698 .