Morphine alkaloids derived from the opium poppy have long been used as analgesics. Codeine, the methyl ether of morphine, is a naturally occurring alkaloid with medicinal properties very similar to those of morphine. Thousands of derivatives of morphine have been synthesized and tested for their biological effects. For example, the diacylated derivative of morphine, heroin, is a highly addictive drug. Much effort has gone into understanding how morphine and its derivatives function.Studies have shown that certain common structural features of alkaloids are required for the compound to exhibit biological activity. These structural requirements are summarized by the so called "morphine rule":Demerol and methadone, shown in Figure 2, are two synthetic alkaloids designed to satisfy the "morphine rule." Synthetic alkaloids such as these have been found to mimic certain physiological properties of morphine and its derivatives, and have found pharmacological application due to other, more desirable biological effects. Methadone has been used widely in the United States and Great Britain as a treatment for heroin addiction; it reduces the physical symptoms accompanying withdrawal without producing many of the other effects of heroin. Meperidine(demerol)Figure 2Hofmann elimination involves methylation of the amine nitrogen followed by elimination (E2). Which of the following represents a possible product of one sequence of Hofmann elimination on Meperidine (demerol)?
Answer(s): B
Hofmann elimination proceeds through exhaustive methylation of the amine to the quaternary ammonium compound followed by elimination. Choice B shows a structure that has the double bond and the tertiary amine produced by Hofmann elimination.Note that the alkene bond could have formed on the other side of the nitrogen by an equally likely elimination giving the product shown below:Choice A is incorrect because the structure indicated is the intermediate of the Hofmann elimination. Choice A shows the structure following methylation but prior to elimination.Choice C is incorrect because the amine is not fully methylated (to the tertiary amine). Note the similarity between choice C and the valid elimination product shown above.Choice D is incorrect because it does not show the cleavage of the N-C bond that occurs in a Hofmann elimination (as described in the question stem).
Morphine alkaloids derived from the opium poppy have long been used as analgesics. Codeine, the methyl ether of morphine, is a naturally occurring alkaloid with medicinal properties very similar to those of morphine. Thousands of derivatives of morphine have been synthesized and tested for their biological effects. For example, the diacylated derivative of morphine, heroin, is a highly addictive drug. Much effort has gone into understanding how morphine and its derivatives function. Studies have shown that certain common structural features of alkaloids are required for the compound to exhibit biological activity. These structural requirements are summarized by the so called "morphine rule":Demerol and methadone, shown in Figure 2, are two synthetic alkaloids designed to satisfy the "morphine rule." Synthetic alkaloids such as these have been found to mimic certain physiological properties of morphine and its derivatives, and have found pharmacological application due to other, more desirable biological effects. Methadone has been used widely in the United States and Great Britain as a treatment for heroin addiction; it reduces the physical symptoms accompanying withdrawal without producing many of the other effects of heroin.Meperidine (demerol)Figure 2Researchers have discovered that the stereochemistry of the alkaloids is critical to their physiological effects. For example, (-)-methadone produces powerful analgesic effects while (+)-methadone produces no effect. Which of the following is the most likely Explanation: for this difference in activity?
Enantiomers like (-)-Methadone and (+)-Methadone do not differ in their physical or chemical properties. They can only have different physiological effects by interacting with a stereospecific receptor a receptor that is itself chiral.Choice A is incorrect because (+)-Methadone would follow all of the morphine rules because it has the same connectivity of atoms as (-)-Methadone.Choice C is incorrect because analgesic effects are physiological and would not depend on the rotation of light.The rotation of plane polarized light is used as a test for chirality. The light would rotate an equal degree measure, but in the opposite direction.Choice D is incorrect because the passage states that methadone is a synthetic alkaloid. Even if it was naturally occurring, Choice D might be true but would still not explain the difference in physiological activity.
The hydrogens of alkanes have pKa values that are over 30 or 40. In contrast, the -hydrogens of aldehydes and ketones have pKa values that range from 19 to 21. These fairly acidic -hydrogens can be removed by strong bases to form anions called enolates. The enolate ions are strongly stabilized by resonance. Protonation of the enolate at oxygen produces an enol. Interconversion between the keto and enol forms is called tautomerization and is illustrated in Figure 1. The keto form is usually highly favored.Figure 1Keto-enol tautomerization has some interesting consequences. For example, if a ketone is treated with acid or base in a solvent of D2O (heavy water), all of the - hydrogens will be exchanged for deuterium. This reaction is shown in Figure 2. Figure 2Another consequence of keto-enol tautomerization is the racemization of chiral -carbons. In the enol form, the -carbon adopts a planar configuration and is no longer chiral. Tautomerization back to the ketone produces a racemic mixture of products. This is shown in Figure 3.Figure 3A scientist attempts to follow the progress of the -deuteration shown in Figure 2 using proton NMR. Which of the following would be the best indicator that the reaction has proceeded to completion?
Answer(s): D
Proton NMR is used to identify the number and environments of 1H nucleI). Therefore, deuterium, 2H, will not appear on the NMR and as the alpha hydrogens are replaced with deuterium, the signals will disappear.Choice A is incorrect because a peak at 9.8 ppm, which, by the way, is rarely a singlet, indicates an aldehyde proton. No aldehydes are present here.Choice B is incorrect because a quadruplet in the alkane range (1.0-2.0) indicates hydrogens with 3 neighboring hydrogens, leading to splitting.Choice C is incorrect because a peak between 3.0-4.0 may indicate an alcohol. A doublet indicates splitting by a single neighboring hydrogen.
The hydrogens of alkanes have pKa values that are over 30 or 40. In contrast, the -hydrogens of aldehydes and ketones have pKa values that range from 19 to 21. These fairly acidic -hydrogens can be removed by strong bases to form anions called enolates. The enolate ions are strongly stabilized by resonance. Protonation of the enolate at oxygen produces an enol. Interconversion between the keto and enol forms is called tautomerization and is illustrated in Figure 1. The keto form is usually highly favored. Figure 1Keto-enol tautomerization has some interesting consequences. For example, if a ketone is treated with acid or base in a solvent of D2O (heavy water), all of the - hydrogens will be exchanged for deuterium. This reaction is shown in Figure 2.Figure 2Another consequence of keto-enol tautomerization is the racemization of chiral -carbons. In the enol form, the -carbon adopts a planar configuration and is no longer chiral. Tautomerization back to the ketone produces a racemic mixture of products. This is shown in Figure 3.Figure 3The IUPAC name for the reactant in Figure 3 is:
Answer(s): A
The structure can be drawn as shown below:The longest chain has 5 carbons and this compound will be named with the pent- prefix. This is enough to select Choice A. Numbering proceeds to give the lowest numbered ketone (the highest priority group in this compound).Choice B is incorrect because it does not number the longest chain correctly, naming the molecule as an ethyl substituted butanone.Choice C is incorrect because it too does not number the longest chain correctly.Choice D describes an impossible molecule.
The hydrogens of alkanes have pKa values that are over 30 or 40. In contrast, the -hydrogens of aldehydes and ketones have pKa values that range from 19 to 21. These fairly acidic -hydrogens can be removed by strong bases to form anions called enolates. The enolate ions are strongly stabilized by resonance. Protonation of the enolate at oxygen produces an enol. Interconversion between the keto and enol forms is called tautomerization and is illustrated in Figure 1. The keto form is usually highly favored.Figure 1Keto-enol tautomerization has some interesting consequences. For example, if a ketone is treated with acid or base in a solvent of D2O (heavy water), all of the - hydrogens will be exchanged for deuterium. This reaction is shown in Figure 2.Figure 2Another consequence of keto-enol tautomerization is the racemization of chiral -carbons. In the enol form, the -carbon adopts a planar configuration and is no longer chiral. Tautomerization back to the ketone produces a racemic mixture of products. This is shown in Figure 3. Figure 3Which of the following ketones will have the most acidic -hydrogen:
Alpha hydrogens are relatively acidic because of resonance stabilization as shown below. The acidity of the alpha hydrogens will be increased by proximity to electron withdrawing groups.The chloride groups in choice B are electron withdrawing and will help stabilize the negative charge. Choice A is incorrect because dimethylketone has no additional electron withdrawing groups.Choice C is incorrect because an amine is an electron donating group and would tend to decrease the acidity of the alpha hydrogen.Choice D is incorrect because there is no alpha hydrogen to be removed.
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