Polarimetry optical rotation techniques

Part—IV has been entirely devoted to various Optical Methods that find their legitimate recognition in the arsenal of pharmaceutical analytical techniques and have been spread over nine chapters. Refractometry (Chapter 18) deals with refractive index, refractivity, critical micelle concentration (CMC) of various important substances. Polarimetry (Chapter 19) describes optical rotation and specific optical rotation of important pharmaceutical substances. Nephelometry and turbidimetry (Chapter 20) have been treated with sufficient detail with typical examples of chloroetracyclin, sulphate and phosphate ions. Ultraviolet and absorption spectrophotometry (Chapter 21) have been discussed with adequate depth and with regard to various vital theoretical considerations, single-beam and double-beam spectrophotometers besides typical examples amoxycillin trihydrate, folic acid, glyceryl trinitrate tablets and stilbosterol. Infrared spectrophotometry (IR) (Chapter 22) essentially deals with a brief introduction of group-frequency... 

Light scattering techniques Optical rotation-polarimetry Refractive index Infrared spectro-photometry Infrared process analyzers Microwave spectroscopy Gamma ray spectroscopy Nuclear quadrupole moment... 

Polarimetry With the help of the instructor or assistant, obtain the observed optical rotation a of the pure (+)-carvone and (—)-carvone samples. These are provided in prefilled polarimeter tubes. The specific rotation [a]p is calculated from the relationship given in Technique 23, Section 23.2. The concentration c will equal the density of the substances analyzed at 20°C. The values, obtained from actual commercial samples, are 0.9608 g/mL for (+)-carvone and 0.9593 g/mL for (—)-carvone. The literature values for the specific rotations are as follows = +61.7° for (+)-carvone... 

The second approach, the so-called direct method, consists of the direct determination of enantiomers immersed in a chiral environment. A diversity of techniques has been used to determine enantiomeric composition in samples. Polarimetry, NMR using chiral solvating agents (CSAs), or the different chromatographic and related techniques are the most popular. Polarimetry is still broadly applied in organic chemistry laboratories at least as a semiquantitative method. The general, easy-to-perform, and nondestructive characteristics of polarimetry are properties that justify its use. However, limitations such as the need to know the specific optical rotation for the compound of interest, the inherent low sensitivity, and the possible inaccuracies related to the presence of impurities or to the low specific rotation of certain compounds cannot be overlooked. 

The interaction of polarized light with chiral compounds is of great interest since chiroptical techniques are extremely useful as methods of characterization. It is equally true that although most scientists are aware that enantiomerically rich solutions will rotate the plane of linearly polarized light, the origins of this effect are not as simple as might be imagined. In this first article, the phenomena of polarimetry and optical rotatory dispersion will be discussed. A subsequent note will concern the related phenomenon of circular dichroism. 

The fundamental requirement for the existence of molecular dissymmetry is that the molecule cannot possess any improper axes of rofation, the minimal interpretation of which implies additional interaction with light whose electric vectors are circularly polarized. This property manifests itself in an apparent rotation of the plane of linearly polarized light (polarimetry and optical rotatory dispersion) [1-5], or in a preferential absorption of either left- or right-circularly polarized light (circular dichroism) that can be observed in spectroscopy associated with either transitions among electronic [3-7] or vibrational states [6-8]. Optical activity has also been studied in the excited state of chiral compounds [9,10]. An overview of the instrumentation associated with these various chiroptical techniques is available [11]. 

The instructor may ask you to combine your remaining resolved naproxen with other students for determining the rotation of your (S)-naproxen by polarimetry. If so, your instructor will supply instructions. (S)-Naproxen has an observed specific rotation of +66°. The solvent, chloroform, will be used as the solvent, unless you are told otherwise. Calculate the % optical purity (% enantiomeric excess) for your sample and compare the results with the chiral HPLC results. Remember that the sample may only contain about 82% of the (S) enantiomers (Technique 23, Section 23.5) so you will not obtain a value of +66° from the polarimeter. 

To this point, all of the experiments that we conducted have supported the biosynthetic hypothesis outlined at the top of Scheme 2 (see Section 2.2). However, there remained a mildly vexing set of data from the 2009 report describing the flinderoles that on the surface seemed to contradict the possibility of an enzyme-free acid-promoted dimerization of borrerine. While the borreverines and related compounds like yuechukene were reported to be isolated as racemates, the flinderoles A-C were reported to have specific rotations of —6.4, —7.3, and —7.4 (c = 0.03), respectively. Since enantioenrichment implies an element of chiral control, and all acids studied in the dimerization produced racemic compounds, the report of optical activity in the natural samples suggested some biological involvement in their formation. Of note, however, is the low concentration used for the polarimetry experiments, which is not an extremely sensitive analytical technique. Furthermore, all three compounds exhibited similar specific rotations, even the two diastereomers. These... 

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