ORGANIC CHEMISTRY II
ORGANIC CHEMISTRY II CH 310N
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This 58 page Study Guide was uploaded by Brady Spinka on Monday September 7, 2015. The Study Guide belongs to CH 310N at University of Texas at Austin taught by Jonathan Sessler in Fall. Since its upload, it has received 228 views. For similar materials see /class/181865/ch-310n-university-of-texas-at-austin in Chemistry at University of Texas at Austin.
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Date Created: 09/07/15
Exam II will cover chapters 1518 inclusive but only 151 and 152 Usual Of ce Hours Today 3430 pm Wel 5428 Review Session Tonight 5 pm in Wel 2122 But No Of ce Hours Tomorrow Sorry Recommended Problems new Recommended Problems new EVERYTHING IN CH 17 EVERYTHING IN CH 18 But if pressed for time start with But if pressed for time start with 17717817121713 1861881891811 171717181723 183 18418191821 17261727 18241826 1827 very useful 1729 17321740 1828 1829 amp 1830 as mechs 18321834 18391841 18451853 Chapter 18Finishing Up Carboxylic Acid Derivatives We are studying ve classes of organic compounds derived from acids by dehydration Under the structural formula of each is a drawing to help you see its formal relationship to the carboxyl group O O O O O R3CI RcoER39 RcOR39 R39c39NH 2 RC EN An acid chloride An acid anhydride An ester An amide A nitrile o o I I o m II I The enol of an amide Reactions ofAeyl Derivatives W Can React to Give Others Below it RCCI O SO can each ofthese RCOCR39 W 1 I RCOR O RENR Nucleophilic Acyl Substitution With an anion as nucleophile 65 R Y O C o x lg X R X Y R Y This is a very IMPORTANT general reaction Understanding the mechanism allows one to explain and predict a large body of organic chemistry Nucleophilic Acyl Substitution with uncharged nucleophile 6zH fl HY R H fl C C R f R Y Y Protonated intermediates N0 anions in neutral or acidic media Hydrolysis osz39trz39ZeS in Acid Hydrolysis of nitriles resembles the hydrolysis of amides The reaction is irreversible Ammonia is produced and is protonated to ammonium ion in acid solution 0 II RCN 2H20 H RCOH NH4 Recall Cyanohydrins Hydrolysis of nitriles is a valuable route to carboxylic acids 0 OH HO O H l H2 804 H 20 I II CH WV CECEN Tr CHCOH water H 2Hydroxyphenyl Benzaldeh de Benzaldehyde y cyanohydrin acetic acud Hydrolysis ofNitrileS in Base In basic solution the carboxylic acid product is deprotonated to give a carboxylate ion RCN H20 H0 RCO NH3 Base Hydrolysis of Nitriles Hydrolysis of a cyano group in aqueous base involves initial formation of an imidic acid which undergoes ketoenol tautomerism to give an amide OH COH I o o 00 I o 39 H o 9 QC 91 gtRc N K 39 gt RC NH 29H An imidic acid IO RC N H gt RC 5 in An imidic acid An amide enol keto Acid Hydrolysis of Nitriles 30H oH CN H gt RCNH H20 Same imidic acid enol form of amide formed under base promoted hydrolysis conditions Base Catalyzed Hydrolysis OfAmideS Hydrolysis of an amide in aqueous base requires 1 mol of base per mol of amide O 0 H20 ll CH3CNH NaOH heat CH3CO Na H2N NPhenylethanamide Sodium acetate Aninne Review from last time Base Catalyzed Hydrolysis ofAmideS Hydrolysis of an amide in aqueous base is divided into three steps Step 1 addition of hydroxide ion to the carbonyl carbon z EIS R Ciillzjz H gt R CI Hz 9 H Tetrahedral carbonyl addition intermediate Base Catalyzed Hydrolysis ofAmideS Step 2 collapse of the intermediate to form a carboxylie acid and ammonia 0 0 RNH2 H o H R4 NH3 36H V4 OH QH Tetrahedral carbonyl addition intermediate Base Catalyzed Hydrolysis OfAmideS Step 3 proton transfer to form the earboxylate anion and water Hydrolysis is driven to completion by this acidbase reaction 0 R44quot j gt R44quot H Q H QH z Review from last time Acid Mediated Hydrolysis of Amides Acidcatalyzed hydrolysis of an amide is divided into three steps Step 1 protonation of the carbonyl oxygen II 6H 6H R CNHZ HCO H gt u r 39139 R c NH2lt gt R CNH2 H20 Resonancestabilized cation Acid Catalyzed Hydrolysis of Amides Step 2 addition of H20 t0 the carbonyl carbon followed by proton transfer DH proton transfer quotOH II R W O H gt R C NH2 MgtR C NH3 I I 39 Tetrahedral carbonyl addition intermediate Acid Catalyzed Hydrolysis OfAmideS Step 3 collapse of the intermediate coupled with proton transfer to give the carboxylic acid and ammonium ion 0 RH o JH f 0 on R I NH3 R I NH3 RCQH NH4 9H 9H Grignard reagents react with esters RI R39 quot dieth I 5 9CH3 y 5 ether RCQCH3 MgX O orTHF O MQX but species formed is THF Q unstable and dissociates under the reaction conditions to form a ketone Grignard reagents react with esters R39 5 9CH3 dlethyl lot 5 ether RCQCH3 ng g 91 ng CH3OMgX This ketone then goes onto react with a second mole of I the Grignard reagent to R R give a tertiary alcohol If E this next step is unclear please go back and review 0 Example ff ZCH3MgBr CH3ZCHCOCH3 1 diethyl ether 2 H30 Two of the groups OH attached to the tertiary I carbon come from the CH32CHCCH3 Grignard reagent The I other comes from the CH3 main chain of the 73 ester Addition ofGrignard Reagents t0 Nitriles We discussed this in class last lecture lng lH R39M x H o RCN g RCR39 2 RCR39 diethyl ether Grignard reagents add to carbonnitrogen triple bonds in the same way that they add to carbon Oxygen double bonds The product of the reaction is an imine Facile deprotonation gives an unreactive anion Protonation as a separate step releases the ketone Addition ofGrignard Reagents t0 Nitriles I ng lH R39M X H o RCEN g RCR39 2 RCR39 diethyl ether H30 Imines are readily hydrolyzed to ketones Therefore the reaction of Grignard fl reagents with nitriles can be used as a RCR synthesis of ketones Example CEN CH3Mg F30 1 diethyl ether 2 H3O heat CCH3 Organolithium Reagents and Diorganocuprates Organolithium compounds are even more powerful nucleophiles than Grignard reagents and they react with esters to give tertiary alcohols often in higher yields O OH 1 2 R CuLI H3cOJJR 1 RR 2 H20 HCI 1R1 Fine Print While they act as nucleophiles diorganocuprates are mechanistically more complex they do other reactions that are impossible for normal nucleophiles This chemistry appears in Section 2 of Chapt 15 the part you are responsible for Acid chlorides react with diorganocuprates Gilman reagents to give ketones The reaction is carried out at 78 C and at these temperatures the ketone doesn t react further with the Gilman reagent to generate a tertiary alchol This is because the tetrahedral carbonyl intermediate is stable at these low temperatures In addition diorganocopper reagents react readily only With the activated acid chloride They do not react with aldehydes ketones esters amides acid anhydrides or nitriles O O39 Li O H 0 CI CH32CuLI CI CH3 2 CH3 0 o o ether 78 O O O Reduction of Acid Derivatives With LiAlH4 Acids page 620621 Esters page 672 Please do mechanism for phenyl propionate Amides see page 673 Please do mechanism for N methylbutanamide Nitriles Selective Reductions with NaBH4 LiAlH4 Reduction of Esters Carbonyl compounds are most often reduced by transfer of hydride H from boron or aluminum As for carboxylic acids LiAlH4 is used to reduce esters to alcohols O 1 LiAIH4 ether H C R 2 H20 HCI Mechanism 0 O O H U LiAlH4 Reduction of Amides Lithium aluminum hydride can be used to prepare primary secondary or tertiary amines depending on the degree of substitution of the amide O 1 LIAIH4 ether H3CNJJR H3CNR Tertiary 2 H20 CH3 CH3 0 1 LiAIH ether H3CNJJR 4 H3C NR Secondary H 2 H20 H O 1 LIAIH4 ether R Primary HZNJkR gt HZN 2 H20 Mechanism AIH3 k we 0 o HsCshlb H gt Hsc LvR Hscv R HH H H 39 H3Clltl lR gt H3ch lR G H H H H Note Deprotonation An iminium ion may occur prior to elimination meaning reprotonation would occur following the final reduction step On an exam you will get full credit for both scenarios LiAlH4 Reduction of Nitriles The cyano group is reduced to a primary amine by lithium aluminum hydride This is a useful preparation of primary amines 1 LiAIH4 ether R NW 2 H20 R H2N Since nitriles may be made by SN2 chemistry as well as dehydration of amides this is a very help in synthesis Selective Reductions Sodium borohydride reacts very slowly with esters Because of this low reactivity it is possible to reduce an aldehyde or ketone in the presence of other carbonyl derivatives Altering the structure of reducing agents also affects reactivity Another selective reagent DIBAlH was discovered in this manner DI BAH Diisobutylaluminum hydride DIBAIH at 78 C selectively reduces esters to aldehydes at 78 C the tetrahedral intermediate does not collapse and it is not until hydrolysis in aqueous acid that the carbonyl group of the aldehyde is liberated 0 1 CH CHCH AlH at780 o 0 CH3 2 DilH3O H 039 A1R2 Stable at low I C 0 CH3 temperature H Hofmann Rearrangement R39 Speci c Example Showing Retention of Stereochemistry Br2 NaOH H20 E H gt R IrI H H Ph 390 Br2 NaOH H20 Ph HW ll H gt W Iv H H30 H H3C H Good News Mechanism on next page is NOT on Exam II but on Final O OH39 390 Brgr 390 U RJ ij H R iilo R ii Br Br H H H 36 H20 H RJI N Br OH39 R quot iiii R N Br Ill Br an acyl nitrene R NJI OH an isocyanate H an acyl a carbamic aCId nitrene unstable species H3O K O quotmi IQ gt R iiJ H co2 W H H a carbamic acid a primary amine m I ve made so many mistakes that i noww mlnk of my Illa as pun researchquot Let s use Remaining Class Time to Practice Synthesis This is a great way to review Organic Synthesis The Trick As We Discussed Brie y Last Semester Is to Employ Retrosynthetic Analysis Examples From Last Semester 0 M M gt 2 H050 Br 2 heptanone W Br H3C CEC 2 transpentene HCEC Z BrCHs Practice Problems General Rule Any Viable synthesis will be accepted at this stage 1 HO Secondary Points Carbonyl gt alkene conversion is possible by Wittig reaction Tertiary alcohol with two identical substituents looks like product of Grignard ester OH Question we must ask How can we get this product in one step from anything Is this anything easier to make How can it be made in one step Etc Solution 1 CH2PPh3 HZCrO4 30 o HO HO HO H MeOH 09 2 MeMgBr Aigt heat O H H20 I OH THE AUTHOR LlST 6 CREDIT WERE CREDIT ls The third au hor 7 The secondtol ast Thefquotquot539t gmm First year39student who actually did author Sen39m Era E39Udem 3 the experiments performed the Ambitious assislant m quot393 PTDJBCT Made 1393 analxsis and wrote tha whale pa er fessor ur oatdun w or QUFES Than 5 hemg thlrd author Is fa lnsligatedplhe paper Michaela C Lee E F Sapl P l Qiacl mls T Ulivelra L Smith B S The last author The head honmlm Has n t even read he Vaper but hey he got the fun In and hIS famous name wul gel the paper accepled The second author Grad student mrthe ab that has nothing a do with lhls project bul was Included because helshe hung around the grou meetian usually for the foo The middle authors Authcr names nobody really reads Rammed fur undergrads and technical starquot ma cum Cc quot9005 wwwphd omic5rcm Problem 2 CH3 OH 1 CH2CHZCuLI 1 CH3Li H2 B gt HZCZC C C C CH3 2 W H20 2 W H20 H H CH3 Identify A and B Solution 2 CH3 0 CH OH I H2 1CH2CHZCuLi fH3HZ 1CH3Li l 3H2 l Br C C CH gt H2cc c c CH HZCZC C C C CH3 l 2 W H20 H 2 W H20 H H CH3 CH3 CH3 A B Note how the lithium diorganocuprate does not react with the aldehyde See page 670 of the Brown amp Foote text Problem 3 Synthesize Novacaine from benzene Any Viable synthesis is acceptable at this stage Obviously an efficient highyielding and cheap synthesis is better Note The usual rule unless stated otherwise is that you may use as building blocks any stable organic compound with 4 or fewer carbon atoms NH2 Question we must ask How can we get this 3 product in one step om O O anything Is this R anything easier to One step back could be n1tro N make HOW can it be de YaUVC 7 made in one step Etc Amme and ester formation will be key Steps Novacaine Solution 3 Brz AIBr3 HNan H2504 No2 LNJ Br H2 Ni gt O O C gt base No2 1Mgg2 gt 2 002 3 H H20 ANJ NH2 Novacaine Possible problem step HOCO H2N OH H heat No2 Note how ester resists hydrogenation in last step But this proposed synthesis is a bit long and has at least one potential problem step Can we do better Solution 3 alternative Br Br Br2 AIBr3 HNan H2504 3 a No2 N N S H o o C o 0 N02 NH2 Novacaine But how to make this 1 Mg I2 OH 2 002 H heat 3 H H20 0 Note how we use a socalled convergent approach to increase ef ciency Problem 4 0 HOME 0 N Secondary Points Carbonyl gt imine conversion Question we must ask is easy if carbonyl is in hand HOW can we get this Ac1d to alcohol convers1on can product in one step om be ach1eved by reductlon but anything Is this needed reagents would reduce anything easier to imine So must come before make HOW can it be that made in one step Etc Carbonyl of ketone or aldehyde can be protected This can t be done for imine Solution 4 o o O H O O 1 UA39H4 HCI H20 NH3CH3 HOV HOnN o o o l 2 H H2O as necessary HO N NIK O isomer Finishing Chapter 21 Chapter 16 Intro to Carbonyls Chapter 15 Highlights Grignard and Gilman reagents Lecture 11 Sessler 310N Recommended Problems CH s 20 21 204 206 2072010 2016 2017 20192032 2043 20462048 212 214 215 217219 2111 21142122 21242126 21302143 Exam 1 will cover spectroscopy MS IR NMR UVVis and Aromaticity Chapts 1214 part of 23 20 and 21 121 2 NOTE NO OFFICE HOURS TOMORROW SORRY However There is a review session Tonight 5 pm We12122 Di and Polysubstitution 0 Existing groups on a benzene ring in uence further substitution in both orientation and rate 0 Orientation certain substituents direct preferentially to orlho amp para positions others direct preferentially to meta positions substituents are classi ed as either orthopara directing or meta directing Di and Polysubstitution 0 Rate certain substituents cause the rate of a second substitution to be greater than that for benzene itself others cause the rate to be lower substituents are classi ed as activating toward further substitution or deactivating preventing or slowing further substitution Di and Polysubstitution o OCH3 is orthopara directing and activating oTHE MECHANISTIC EXPLANATION ACCOUNTING FOR THIS OBSERVATION WAS PRESENTED IN CLASS THURS OCH3 OCH3 OCH3 B B r gt HBr CH3C02H B r anisole obromo pbromo anisole anisole 4 96 Di and Polysubstitution 0 N02 is meta directing and deactivating NO 2 HNO 3 ZS 4 NO 2 NO 2 NO 2 Nitro 0 Q NO 2 benzene NO 2 NO 2 mDinitro oDinitro pDinitro benzene benzene benzene J 93 Y Less than 7 comblned oTHE MECHANISTIC EXPLANATION ACCOUNTING FOR THIS OBSERVATION WAS PRESENTED IN CLASS THURS
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