MEDICINAL CHEMISTRY I EXAM #1

Transcription

1 MEDICIAL CEMISTRY I EXAM #1 1 September 30, 2005 ame SECTI A. Answer each question in this section by writing the letter corresponding to the best answer on the line provided (2 points each; 50 points total) 1. The compound shown below: I Is a base with a pk b value of 10 II Is 2-Imidazoline III Is a base with a pk b value of 3 2. The functional group in the compound illustrated below: I Is a carbamate II Is an acid with a pk a value of 12 III Is a carbonate 3. For the structures illustrated below: I Compound A is a stronger acid than S S compound B 3 C 3 C II Compound B has a larger log P value than A B compound A III Compound B has an electron-donating substituent para to the hydroxy group

2 4. The drug illustrated below: I as a benzyl group attached to the nitrogen 2 C C C 2 II Contains a lactone functional group III as a conjugate acid form with a pk a value of The compound illustrated below: I as a conjugate base form with a pk b Br value of 10 II Is 50% ionized at p 4 III Is 100% ionized at all p values 6. For the compound shown below: 3 C Cl C C C 3 C Cl I The hybridization of the carbon with the two chlorines is sp 2 II The chlorines are in a plane that is perpendicular to that of the methyl groups III The hybridization of the carbon with the two methyl groups is sp 2

3 7. For the compounds illustrated below: C 3 I Structures A and B represent the same compound C 3 II Structures A and B are enantiomers Cl Cl III Structure B has the R-configuration A B 3 8. The drug illustrated below: I Is 5,5-diphenylimidazolidine-2,4-dione II Contains a group that is an acid with a pk a value of 9 III as the pro-s phenyl group oriented behind the paper 9. The compound illustrated below: I Contains a cyclic ether II Is 2-tetrahydrooxecin-2-one III Is tetrahydrooxonin-2-one 10. Consider the two structures shown below: C 3 C 3 3 C C 3 A B I Structures A and B represent the same compound II Structure B would T be optically active III Structures A and B represent diastereomers

4 4 11. For the compound shown below: I The methyl groups are trans- to one another 3 C II The three atoms that make up the epoxide ring (two C 3 carbons and the oxygen) are all in one plane III The methyl groups are cis- to one another 12. The compound illustrated below: C 3 Br I Is 50% ionized at p 9 II Is 90.9% ionized at p 9 III Is 100% ionized at p The compound illustrated below: I Is 50% ionized at p 4 C 3 I II as a conjugate base form with a pk b value of 10 2 C C 3 III Contains a quaternary ammonium group C The compound illustrated below: C 3 C 3 C 2 C I Contains a conjugated system II as three double bonds with (E)- stereochemistry III as two double bonds with (E)- stereochemistry and one with (Z)- stereochemistry

5 5 15. The structure illustrated below: C 3 C 3 I Is the lowest energy conformation of butane II Is drawn as a gauche conformation III Is the highest energy conformation of butane 16. The compound illustrated below: I Is aromatic II Is 2,3-dihydro-1,3-oxazepine III as a basic group with a pk b value of For the structures illustrated below: I A and B are resonance structures C 3 C 3 II A and B are esters III Structure B is the enol tautomer of structure A A B 18. For the two compounds illustrated below: 2 2 I Compound B is a stronger base than compound A 2 3 C II Compound A has a larger (more positive) log P value than compound B A B III Compound A is a stronger base than compound B

6 6 19. The compound illustrated below: C 3 I as a maximum of 2 possible stereoisomers that could be drawn 3 C II as exactly two chiral centers III as a maximum of 4 possible stereoisomers that could be drawn 3 C 20. Consider the structures shown below: C 3 3 C I Compound A contains an amidine with (Z)- stereochemistry C 3 C 3 II Compound B has a conjugate acid form with a C 3 C 3 pk a value of 11 A B III For compound A the lone pair of electrons on the double-bonded nitrogen would be in the same plane as the methyl group attached to that same nitrogen 21. The compound illustrated below: I Is 1,4-dihydro-1,2,3-triazine II Is an aromatic heterocycle III Is 1,4-dihydro-1,2,3-triazole 22. In the structure shown below: 3 C I The methyl group is located at the 1-position II The hydroxyl groups are trans- to one another III The hydroxy groups are located at the 9- and 10-positions

7 23. For the structures shown below: C 3 I Structure A is cis-1,3-dimethylcyclohexane C 3 C 3 II Structure B is cis-1,3-dimethylcyclohexane III Structure B is lower in energy than structure A C 3 A B The compound illustrated below: I Is phenyl acetate C 2 C C 3 II Is methyl benzoate III Is benzyl acetate 25. The compound illustrated below: I Would form a monohydrochloride salt with a pk a C 2 C 2 C 2 value of 9 II Contains a sulfoxide functional group III Would form a monohydrochloride salt with a pk a value of 2 S

8 SECTI B. 14 Points Total For the following pair of compounds assign the proper stereochemistry (R or S) at each chiral center in each molecule. Then indicate on the line the relationship of the compounds to each other by writing the word EATIMER, DIASTEREMER, R SAME CMPUD. (5 Points). C 2 2 C C 3 C 3 2. Assign the stereochemistry of the compound shown below by clearly writing the letter E- or Z- next to each assignable double bond, as appropriate. (2 Points). 3 C 3 C C 3 C Cl Br 3. The following compound is the triacetate derivative of the sugar D-ribose. It has an optical rotation [α] = and a melting point of 88 C. Indicate the absolute configuration at each chiral center of D-ribose (R or S). Then answer the questions below pertaining to Compound B. (7 Points). C C 2 C C 2 D-Ribose Compound B a) What is the relationship (enantiomer, diastereomer, same compound) of Compound B to D-ribose? b) Would the optical rotation of Compound B be: +19.7, -19.7, 0, or is there not enough information to determine it? c) Explain your answer from question b). d) Would the melting point of Compound B be: 88 C, -88 C, 0 C, or not enough information to determine?

9 SECTI C. For each of the following fill in the blank with the appropriate term. (6 Points). a) structures are two or more structures that have the same composition but differ only in the way the electrons are distributed. b) Compounds that are cyclic and flat, in which each atom in the ring has a p-orbital, and in which the total number of π-electrons is equal to 4n (where n is 0,1,2,...) are called. c) The polarization of a sigma bond as a result of electronegativity differences between the atoms that make up the bond is called an effect. d) Distinct configurations of molecules that result from rotations about single bonds are called. e) In a compound such as ethane, when the hydrogens of one carbon are lined up directly behind the hydrogens of the second carbon that arrangement is called. f) on-superimposable mirror image isomers of a compound are called. 9 SECTI D. For each of the following pairs of compounds circle the one that has the higher log P. (5 points). a) C 3 C 3 b) F F c) C 3 2 C 3 C 3 C 3 3 C C 3 d) C 2 C 2 C 3 e) S C3 S C3

10 10 SECTI E. For each of the following systematic names, draw the correct chemical structure, including stereochemistry wherever indicated. Partial credit will be given but you will lose points for incorrect chemical symbols, hydrogens missing from heteroatoms, hydrogens missing from carbons labeled C, and for having too many bonds to an atom (see below for examples). (25 Points). Examples: Incorrect chemical symbol (-1 point each) Fl ydrogen missing from nitrogen (-1 point) n 5 bonds to carbon (- 2 points) Incorrect: Fluorobenzene Piperidine C C C ydrogens missing from carbon chain (-1 point Correct: F or C 2 C 2 C (Diethylamino)ethyl 4-ethoxybenzoate, hydrochloride 2. 1-Imidazo[1,5-c]imidazole, 2,6-bis(2-ethylhexyl)-hexahydro-7a-methyl-

11 3. 6-Allyl-2-amino-5,6,7,8-tetrahydro-4-thiazolo[4,5-d]azepine (S)-2,5-Pyrrolidinedione, 1,3-dimethyl-3-phenyl- 5. (Z)-1-Propanamine, 3-(dibenzo[b,e]thiepin-11(6)-ylidene)-,-dimethyl-, hydrobromide