Chem 353 Final '98

Here is an post-mortem analysis / "how to" for the '98 Final. The questions are split by the sections. At the start of each section are a few suggestions of what to look for or how to tackle the question type.


RELATIVE PROPERTIES:
Identify the controlling feature, which is not always as obvious as it may appear. Look for two pairs of similar systems to compare that have minimal differences in structure.

Qu1: E
Acidity of carbonyl systems is governed by the nature of the electron withdrawing groups near them. The better the group can stabilise the -ve charge in the conjugate base, the enolate, the more acidic the original system. So -CHO (pKa =17) is better than -CO2R (pKa =25) since the -OR portion is also donating towards the C=O), but between two esters is best of all (pKa = 11). This means  iii > i > ii.

Qu2: B
Substituent effects on benzenes. -OMe groups are strongly activating (resonance of the O lone pairs), -Me groups are weakly electron donating (hyperconjugation) and -CN is strongly electron withdrawing (resonance onto the electronegative N), so i > iii > ii.

Qu3: E
All about the relative reactivity of carboxylic acid derivatives, so one can think of the LG ability or the effect the Substituent has
on the electrophilicity of the C=O. LG ability : -Cl > -OMe > -NMe2. Electron withdrawing ability : -Cl > -OMe > -NMe2. So iii > i > ii.

Qu4: A
Aldehyde (i) is more reactive than ketone (ii) towards Nu since it is less hindered and alkyl groups are weak electron donors which also decreases the electrophilicity of the C=O. In the ester, (iii) the -OR is strongly electron donating, further decreasing the electrophilicity.  So i > ii > iii.

Qu5: A
At low temperature, HBr addition occurs under kinetic control  giving 1,2- rather than 1,4- addition, i.e.  (i) > (ii). Product (iii) is not possible from this reaction. So i > ii > iii.

Qu6: AB
Less reactive (softer) systems give more conjugate addition at C than direct addition at O (hard). Enolates (iii) are more less reactive than organometallics and tend to give more conjugate addition. Grignard reagents are less reactive than organolithiums So iii > ii > i.

Qu7: AB
In addition to C=C, the alkene is the Nu, so if the substituents on the double bond donate electrons, it will be more reactive. Here the substituents electron donating ability is -OMe > -Me > -CO2Me. So iii > ii > i.

Qu8: E
Since alkyl groups are weak electron donors, t-butyl- will direct o,p but the large size will favour p over o. Methyl is also o,p directing and due its smaller size, more o will be produced. -NO2 is a m director.  Thus, iii > i > ii.

Qu9: E
Simply count the H a to the C=O. (i) has 3, (ii) has 2 and (i) has 4 ,  so iii > i > ii.

Qu10: AB
In the Diels-Alder reaction the dienophile is usually the electrophile, so electron withdrawing groups enhance the reactivity giving iii > ii > i.



LABORATORY
Read the questions then go back to the data to see what you need to use, pull it all together to get the last question (then review based on that ?)

Qu11: AB.
Two exchangeable H suggest the -NH2 group.

Qu12: A.
IR gives a C=O but no -OH or C-O. H-nmr more like ketone than ester.

Qu13: D
IR gives C=O and -OH. H-nmr very acidic H at 12.8 ppm.

Qu14: E
IR gives C=O more like an ester. H-nmr has deshielded peaks consistent with those in -O-CH systems.

Qu15: C
H-nmr with ArH (near 7ppm) and an exchangeable H suggest the phenol.

Qu16: C
Has ArH (7 - 8 ppm) and aliphatic H (eg. 1 ppm).

Qu17: NONE !
Esters are not very polar, nor very acidic. Only aldehydes and ketones react with 2,4-DNP. The FeCl3 test is for phenols and iodoform for methyl ketones.

Qu18: AB
Monosubstituted, aromatic ester with -OEt group.



PRODUCTS OF SYNTHESIS
Work from the starting materials to the products using the reagents to "see" what product to look for.

Qu19: AC
A Gabriel synthesis of a primary amine. First radical bromination of the benzylic position to get an alkyl bromide. Substitution by the N nucleophile to alkylate on the N. Finally the hydrazine releases the amine AC.

Qu20: A
Bromobenzene will give mainly p-dibromide. Convert to the Grignard and react with CO2, acid work-up to get the p-dicarboxylic acid, A.

Qu21: C
Me group directs nitration o,p then oxidise the benzylic position to the carboxylic acid, so C.

Qu22: E
Nitration, reduction to the amine, diazotise, introduce -CN (Sandmeyer type reaction) and hydrolyse -CN to -CO2H.

Qu23: CE.
Robinson annulation sequence: enolate, conjugate addition, aldol reaction, dehydration giving CE.

Qu24: AE
Cyclohexanol will be oxidised to cyclohexanone. Wittig reaction creates the exocyclic C=C which is converted to the cyclopropane via the Simmonds-Smith reaction.

Qu25: CD
Alkene plus bromine to 1,2-dibromide, which can be eliminated to the conjugated diene, 1,3-cyclohexadiene. This undergoes a Diels-Alder reaction with ethene and is then hydrogenated to give C8 system CD.



STARTING MATERIALS
Need to be able to work backwards.... but again look at the functional groups in the products to think about how you may have got there.

Qu26: B
Not easy ! If you can identify the location of the C4 from the dibromide, then one should be able to see an enolate reaction of diethyl malonate followed hydrolysis and decarboxylation.

Qu27: D or BD
Hoffman elimination of an amine produced by the reaction of ammonia with an alkyl halide. HBr could have reacted with C=C or -OH, but need the methylcyclopentane framework. Both D and BD would react with HBr to give 1-bromo-1-methylcyclopentane.

Qu28: AD
Hydroxylamine reacts with C=O to give the oxime and the first step is an oxidation, so it must be AD.

Qu29: E
Trans 1,2-diols are formed by the reaction of epoxides with water, MCPBA is a peracid which reacts with a C=C to generate the epoxide. So we would have needed the C=C to be produced by elimination of an alkyl halide since we have basic E2 reaction conditions. E2 requires the antiperiplanar arrangement of -H and -LG. AB would eliminate to give the C=C in the wrong location.

Qu30: AE
CO2H produced via the hydrolysis of the -CN, which would have added to cyclopentanone to give the cyanohydrin.

Qu31: BD
Final 2 steps are the Wittig reaction to create the C=C. Steps 1-3 create the anti-Markovnikov alcohol and convert it to bromide which undergoes the substitution by the PPh3.

Qu32: D
Enone product from the basic reaction conditions should suggest the intramolecular Aldol reaction so we needed a dicarbonyl (here the aldehyde - methylketone is needed) from the ozonolysis of the appropriate cycloalkene.



REAGENTS
Look at the functional groups in the starting material and products to try to determine what may have happened. Look at the
reagents in each option to see what effect they would have on the SM....

Qu33: AD
Oxidation of 1o -OH to an aldehyde, so need PDC or PCC.

Qu34:  C
C=O to C=C suggests a Wittig reaction.

Qu35: AB
Allylic bromination requires radical bromination.

Qu36: AE
Conversion of -Br to -CO2H .... use Grignard then CO2 with acidic work-up.

Qu37: B
Reduce  -CO2H to the -CH2OH unit using hydride reagent.

Qu38: BE
Make the tosylate from the alcohol.

Qu39: CE
Preparation of enolate using a strong base.

Qu40: E
C=C to epoxide, use peracid.

Qu41:  BC
Epoxide to diol requires water to act as the Nu.



STEREOCHEMISTRY
Need to know the mechanisms or stereochemistry and regiochemistry of your reactions. Identify the reaction then go from there.... Watch out for the enantiomers, achiral materials will give racemic products.

Qu42: BC
Diels-Alder reaction, syn addition, stereospecific, cis dienophile gives cis products.

Qu43: AE
Tosylate formed with retention at the -OH, but then cyanide displaces the -OTs in SN2 fashion with inversion so the -CH3 and -CN need to be 1,2- and cis.

Qu44: AB
Permanganate reacts with C=C to give cis-1,2-diols.

Qu45: BC
Trans reduction using the dissolving metalt to the trans-alkene, then syn addition to the epoxide.

Qu46: DE
Reacts as HO- and Br+. Br+ adds first to get the bromonium ion then the HO adds at the more stable cationic end with inversion.



APPLIED SPECTROSCOPY
Work through the reaction sequence drawing the products then fit the H-nmr to each of the products looking for the key changes and characteristic peaks at each step.

Qu47: B
Friedel-Crafts acylation gives a para-disubstituted benzene with a methyl singlet at about 2.2 ppm for the methyl ketone.

Qu48: E
Reduce the C=O to an alcohol, look for the O-CH-CH3  peak (quartet at about 4 ppm) and the methyl group becomes a doublet. -OH singlet.

Qu49: AB
-OH to -Br, so similar to 48, but without the singlet for the -OH.

Qu50: D
-Br to -CN, very similar to 49 but the CH-CN is more deshielded.

Qu51: A
Hydrolysis of -CN to -CO2H, look for acid -OH at 12 ppm.