In the Laboratory
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Spectroscopic Properties of Some Simple Esters A Practical Application of Synthesis and Spectroscopy in the Undergraduate Organic Laboratory David P. Brown,* Haris Durutlic, and Didier Juste Department of Chemistry, St. John’s University, Jamaica, NY 11439; *
[email protected] This exercise, the synthesis (1) and spectroscopic analysis of the allyl esters of some aromatic carboxylic acids, consists of a series of experiments that can be used as starting points to examine multiple topics typically discussed in lecture. It was designed for the honors organic chemistry student, but can be easily adapted to fit the regular second-semester organic chemistry course. The primary objective of this exercise is to prepare students for research in organic synthesis. Thus, a series of synthetic transformations are described, incorporating the basic techniques of isolation, TLC and flash chromatographic purification (2), IR and NMR analyses, as well as the method of synthesis involving phase transfer catalysis. These experiments allow the students to monitor the effect of hydrogen bonding on the IR stretching frequencies for the hydroxyl and carbonyl groups, as well as provide them with an excellent opportunity to examine the phenomenon of proton spin coupling in the NMR spectra of simple organic systems.
Use of Various Allyl Halides: Investigation of Reactivity By synthesizing other esters (and ethers) such as methyl, ethyl, propyl, and benzyl from the corresponding allyl halides the instructor will be able to initiate further discussions on the aspects of reactivity and entropy in these reactions. For instance, it can be verified that allyl bromide reacts with nucleophiles by the SN2 process about 40 times faster than propyl bromide. Students can be asked to predict the reactivity of the reaction on benzyl bromide and compare the actual findings with the allylation reactions. We have observed that after about 15 minutes following the addition of the allyl bromide, the reaction mixture became cloudy as a result of the precipitation of potassium bromide. The instructor may opt to use this visible manifestation in a simple rate study.
Experimental Objectives
Esterification Synthesis The main objective of this exercise is to upgrade the laboratory experience of the organic chemistry student to more appropriately reflect the realities of a typical research setting. The experiments can be easily adapted to fit the second-semester organic curriculum or be directly incorporated into the honors organic chemistry program. Students gain practical experience regarding the saponification process, ether formation (3), and the esterification process (Scheme I). In particular, these transformations offer the students an opportunity to encounter the SN2 reaction in esterifications, an alternative to the reversible Fischer approach that is usually applied. Students will appreciate the fact that this approach to an ester will be far more efficient in terms of reaction rate and percent conversion. With the Fischer esterification, it is customary to use an excess of one reagent, usually the alcohol, in an effort to shift the equilibrium towards the product ester. This approach involving the carboxylate (or phenoxide) anion requires stoichiometric quantities and is not subject to the equilibrium constraints as are applicable to the Fischer esterification. An allylic substrate is employed because of the known increased reactivity in SN2 reactions, thereby making these experiments easily performed. Again, this is a direct application of theoretical concepts presented in lectures, as this rate enhancement is understood to be a consequence of allylic delocalization of electrons in the transition state, thus rendering allylic substrates, in general, particularly attractive as electrophiles in SN2 reactions. 1016
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O
KOH (1.1 eq) H2 O reflux
O
KOH (2.1 eq) H2O reflux
1 O
O OⴚKⴙ
ⴚ ⴙ
O K ⴚ ⴙ O K 4
OH 2 allylbromide DMF
allylbromide DMF
O
O
O
O O
OH 3
5 TBDMSCI imidazole DMF
O O OTBDMS 6
Scheme I. The esterification process used in this laboratory. Different organic halides are used to produce various ester products.
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In the Laboratory
Use of Various Organic Halides: E2 versus SN2 A comparison of the phenoxide reactions with alkyl halides such as bromopropane and the similar alkoxide reactions, provides yet another aspect of this exercise that could be probed as a secondary assignment. Students understand that the E2 and SN2 mechanisms compete with each other, and that the SN2:E2 ratio depends on the structures of the nucleophile (base) and the electrophile. Re-lactonization: Enthalpy and Entropy Investigations The possibility for re-lactonization when salts such as 2 and 4 are subjected to mildly acidic conditions, is another related area than can be explored in a group discussion. Questions addressing the entropy and enthalpy factors in such cyclization processes would add more value to the exercise, in that pertinent facts covered in the classroom would be further solidified. Spectral Comparison: Force Constant and Spin Coupling Investigations The acquisition of analytical data also allows the students to enhance their knowledge in IR and NMR spectroscopy. The effects of hydrogen bonding on the carbonyl and hydroxyl stretching frequencies are clearly demonstrated. The observed band widening and shifting to lower absorption frequencies illustrate the fact that hydrogen bonding alters the force constants of both functional groups. From the NMR spectra, the phenomenon of proton spin coupling is exhibited in all the structures generated. Compound 5, Ar⫺CH2a⫺CH2b⫺CO2⫺CH2c⫺CHd⫽CH2e,f, for instance, exhibits first-order coupling relationships between the protons indicated. The methylene protons, a and b, are seen as the expected triplets ( J = 8.1 Hz); proton c appears as a doublet of doublet of doublet, ddd, ( J = 5.7, 1.4, 1.4 Hz); vinylic proton d appears as a doublet of doublet of triplets, ddt, ( J = 17.2, 10.4, 5.7 Hz); proton e, being cis to proton d appears also as a doublet of doublet of triplet, ddt, ( J = 9.5, 1.5, 1.5 Hz); and proton f, being trans to proton d, appearing also as a doublet of doublet of triplet, ddt, ( J = 17.3, 1.6, 1.6 Hz).
Hazards There are no hazards associated with these operational procedures. For the respective reagents, hazardous information is as follows: allyl bromide—flammable and highly toxic, toxic by inhalation, in contact with skin, and if swallowed, irritating to eyes, respiratory system and skin, risk of serious damage to eyes, keep away from sources of ignition; dihydrocoumarin—harmful by inhalation, in contact with skin, and if swallowed, irritating to eyes, respiratory system, and skin; hydrocinnamic acid—avoid contact and inhalation; 2-hydroxyphenyl acetic acid—irritating to eyes, respiratory system, and skin, risk of serious damage to eyes; imidazole— corrosive, causes burns, harmful if swallowed, do not breathe dust; t-butyldimethylsilyl chloride—flammable and corrosive, keep away from sources of ignition, readily hydrolyzed; phenylacetic acid—irritating to eyes, respiratory system, and skin; tetrabutylammonium hydrogensulfate—harmful if swallowed, irritating to eyes, respiratory system, and skin; ether—flammable, may form explosive peroxides, harmful if swallowed, irritating to eyes, respiratory system, and skin, repeated exposure may cause skin dryness or cracking, vapors may cause drowsiness and dizziness; dichloromethane—toxic, harmful by inhalation and if swallowed, irritating to eyes, respiratory system, and skin, may cause cancer, possible risk of harm to the unborn child, readily absorbed through skin, possible dizziness, headache, loss of consciousness, and death at high concentrations; N,N-dimethylformamide—toxic, harmful by inhalation and in contact with skin, irritating to eyes and skin, combustible liquid, readily absorbed through skin; hexanes—flammable, harmful, danger of serious damage to health by prolonged exposure through inhalation, may cause long-term adverse effects, possible risk of impaired fertility, may cause lung damage if swallowed, vapors may cause drowsiness and dizziness; potassium hydroxide—corrosive, harmful if swallowed; causes severe burns, very hygroscopic; ethyl acetate—flammable, irritating to eyes, respiratory system, and skin, repeated exposure may cause skin dryness or cracking, vapors may cause drowsiness and dizziness; magnesium sulfate—hygroscopic, avoid contact and inhalation; silica gel—harmful by inhalation, irritating to eyes and respiratory system, do not breathe dust, hygroscopic.
Conclusion W
These experiments can easily be performed in a standard organic laboratory equipped with magnetic stirrers, stir bars, and heating wells (or mantles) with power controllers. In addition to the assumed availability of an FTIR and FTNMR spectrometer, access to rotary evaporators, high vacuum pumps, and flash chromatography columns will smooth the operation of these experiments. Comparisons among these simple reactions provides hands-on starting points to examine many of the topics discussed in lecture. Using the lecture concepts to explain the laboratory results enhances the learning process and hopefully the retention.
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Supplemental Material
Synthetic procedures, yields, spectroscopic data, and notes for the instructor are available in this issue of JCE Online. Literature Cited 1. Box, V. G. S.; Brown, D. P. Heterocycles 1991, 32, 1273–1277. 2. Still, W. C.; Kahn, M.; Mitra, A. J. Org. Chem. 1978, 43, 2923–2925. 3. Corey, E. J.; Venkateswarlu, A. J. Am. Chem. Soc. 1972, 94, 6190–6191.
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