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The Berkeley Review MCAT Organic Chemistry Part 2 PDF

308 Pages·2011·44.19 MB·English
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Preview The Berkeley Review MCAT Organic Chemistry Part 2

Organic Chemistry Part II Sections V-VIII Section V Carbonyls and Alcohols Section VI Carbohydrates Section VII Nitrogen Compounds Section VIII Organic Chemistry Laboratory Techniques BERKELEY Specializing in MCAT Preparation ERKELEY ® E • V • I • E • W P.O. Box 40140, Berkeley, California 94704-0140 Phone: (800) 622-8827 (80 0) M CAT-TBR Internet: Oxygen Containing Compounds a) Alcohol Properties Section V b) Alcohol Reactivity c) Alcohol Spectroscopy d) Aldehyde and Ketone Properties e) Aldehyde and Ketone Reactivity Carbonyls f) Aldehyde and Ketone Spectroscopy g) Ketals and Acetals and i. Protecting Groups h) Carboxylic Acids and Derivatives Alcohols i. Carboxylic Acids ii. Esters by Todd Bennett iii. Lactones iv. Acid Anhydrides v. Acid Halides 0 O vi. Amides Off /C\0 Carbonyl Reactivity RX XCH3 R CH2 a) Attack at Carbonyl Carbon O O b) Deprotonation of a-Protons c) Oxidation-Reduction Reactions C +1 R CH2 R CH2I Name Reactions O O a) Qrignard Reaction 2more times || b) Aldol Condensation Off. /C\ /C\ c) Claisen Condensation R' 'CH2I ^5~" R CI3 d) Transesterification O O e) Wittig Reaction f) Pinacol Rearrangement Off. g Iodoform Reaction /c\ + cl3 R OH h) Wolff-Kishner Reaction o O Synthetic Logic C + CI3 ^f=^ C. 0 + HCI3 a) Reactions of Acetoacetic Ester R OH R O yeUowoil b) Reactions of Malonic Ester Iodoform Test c) Decarboxylation d) Protecting Groups Carbonyl Biochemistry a) Biological Oxidation-Reduction b) Biochemical Reagents BERKELEY Ur-E-V.KE'W® Specializing in MCAT Preparation Carbonyls & Alcohols Section Goals Recognize the carbonyl functional groups and types of compounds. You must be able to recognize functional groups suchas amides, anhydrides, acidhalides, and °!> especially ketones and aldehydes. You must know which compounds are most reactive towards substitution (which isbasedon the leaving group strength), and mostelectrophilic (which isbased on the electron withdrawing or donating capacity of the functional group). Be able to identify infrared peaks for carbonyl compounds. Carbonyl compounds will have apeak in the infrared spectrum in the area of 1700± cm'1. This will mostlikely beuseful whencomparing twocarbonyl compounds, or identifying an unknown carbonyl compound. You may wish toknow roughly where esters, aldehydes, and ketones fall inthe IR range. Be able to identify common name reactions involving carbonyl compounds. © You must recognize common name reactions from carbonyl chemistry. Included inthis group should * be theAldolcondensation, Grienardreaction, Wittie reaction, and the Claisen reaction. TheAldol and Claisen reactions have biological significance, because they play a role in select biochemical pathways such as glycolysis and beta oxidation. Be able to recognize the acidity of alpha carbons. The carbon alpha to thecarbonyl can bedeprotonated, ifit hasa proton bonded to it. The pKa ofa standard ketone is the range 1/± 2. Once deprotonated, an enolate is formed. The enolate has an equilibrium of its own with the enol structure. The conversion of a ketone into an enol is referred to as tautomerization. Be able to identify ketals, hemiketals, acetals and hemiacetals. Although current accepted nomenclature does notdistinguish between ketals andacetals, youshould * be aware of the functional group. Acetals and ketalsare best described as "doubleethers." They play a major role in sugar chemistry and protecting groups in carbonyl synthesis. Understand the difference between thermodynamic and kinetic enolates. Thethermodynamic enolate is formed underconditions ofhighertemperature wherethe pathway ofgreateractivation energymaybe chosen. Thethermodynamic enolateis the moresubstitutedand thus more stable intermediate which will lead tothe more stable final product. The kinetic enolate is formed underconditions oflower temperature and greater steric hindrance where thepathway of lower activation energy must be chosen. The kinetic enolate is the less substituted and thus less stable intermediate which will lead to the lessstablefinalproduct. Know the mechanisms for acidic and basic carbonyl reactions. The mechanism for transesterification ispresent inbiochemistry andorganic chemistry, soit important that you recognize the steps. Also recognize what catalyst is necessary to carryout the process. Recognize common oxidizing and reducing agents. © a nutshell, oxidation isdefined as thegainofbondstooxygen and/or the lossofbondstohydrogen. n Oxidizing agentsincludeKMn04and K2Cr207. Reduction is definedas the lossofbonds to oxygen and/or the gain of bonds to hydrogen. Reducing agents include LiAlH4 and NaBI-14. Know common reactions by both name and reagents. The AAMC guide lists a series ofreactions that they expect you toknow byname. Iris a eood idea tonot only know the general reaction, butalso the mechanism and reaction conditions. Highlights of this list include the Aldol reaction, the Grignard reaction, the Witting reaction, the iodoform reaction, transesterification, and the Wolff-Kishner reduction. Organic Chemistry Carbonyls and Alcohols Introduction Carbonyls and Alcohols The carbon-oxygen bond isa major part oforganic and biological chemistry. A significant part of organic chemistry on the MCAT involves compounds that contain carbon-oxygen bonds. In the case of carbonyl compounds, the carbon- oxygen 7C-bond is easily broken to form new bonds to the carbonyl carbon and subsequently form a new compound. The carbon-oxygen a-bond found in alcohols and sugars can undergo several reactions, but it is generally not as reactive as the carbon-oxygen rc-bond. Our goalis to organize the vast multitude of reactions involving carbonyl compounds and alcohols. Figure 5-1 shows several types of carbonyl compounds and carbonyl derivatives with which you should be familiar. Types of Carbonyl Compounds 0 O R R R H Ketone Aldehyde R'Ov OR* R'Ov OH R'O OR' R'O OH \/ \/ \/ \/ R H R H R/CVR R/CVR Acetal Hemiacetal Ketal Hemiketal O O O O II II II II R OH[ R OR' R O R Carboxylic Acid Ester Acid anhydride it If If if .'N. R NH2 R N R' H Acid halide Amide Imide NHPh / R R Lactone Phenylhydrzine derivative Lactam ? If /c\ R R CHn Enolate Resonance Forms Figure 5-1 Copyright © by The Berkeley Review Exclusive MCAT Preparation OrgSlIllC ChCllllStry Carbonyls and Alcohols Oxygen Containing Compounds Oxygen containing compounds, because of the highly electronegative nature of oxygen, are very reactive. Much of organic chemistry revolves around alcohols and carbonyls, so it is imperative to get a fundamental understanding of their properties, reactivity,and spectroscopicevidence that supports their existence. Alcohol Properties Because of their ability to form hydrogen bonds, alcohols typically have high boiling points and are generally miscible in water. Alcohols make good solvents as they are often liquids at room temperature and they have a large range between their melting and boiling points. Alcohols are hydrophilic, polar molecules that become less hydrophilic (more lipophilic) as their carbon chain length increases. The smaller alcohols (three carbons or less) are highly water soluble, but as the size of the alkyl group increases, their water solubility decreases. As with all compounds, their physical properties vary with mass and branching, as well as the position of the hydroxyl group. As the molecular mass increases, the boiling point increases, but the effect on the melting point is less clear. As the branching increases, the boiling point decreases. Table 5-1 shows the physical properties of several alcohols, from which the effects of mass, branching, and positioning of thehydroxyl group on the physical properties can be ascertained. Water Isomer IUPAC Name Boiling Melting Density (Common Name) Point Point (g/mL) Solubility (g/lOOmL) CH3OH Methanol 64.6°C -98°C 0.791 High H3CCH2OH Ethanol 78.4°C -115°C 0.789 High H3CCH2CH2OH 1-Propanol (n-Propanol) 97.2°C -127°C 0.804 High (H3Q2CHOH 2-Propanol (i-Propanol) 82.3°C -90°C 0.786 High H3C(CH2)3OH 1-Butanol (w-Butanol) 117.3C -90°C 0.810 8.2 H3CCH(OH)CH2CH3 2-Butanol (sec-Butanol) 99.6°C -115°C 0.806 12.8 (H3C)2CHCH2OH 2-Methyl-l-propanol (f-Butanol) 107.7°C -122°C 0.802 11.3 (H3Q3COH 2-Methyl-2-propanol (f-Butanol) 82.0°C 24°C 0.789 High H3C(CH2)4OH 1-Pentanol (n-Pentanol) 137.6°C -79°C 0.814 2.1 H3CCH(OH)CH2CH2CH3 2-Pentanol 119.3°C 0.809 5.0 (H3CCH2)2CHOH 3-Pentanol 115.9°C 0.815 5.6 H3C(CH2)4CH3 1-Hexanol (n-Hexanol) 157.5°C 0.814 0.8 C6HnOH Cyclohexanol 161.5°C 0.956 2.1 H3C(CH2)6CH2OH n-Octanol 194.7°C 0.817 1 0.3 T able 5-1 Copyright©by The Berkeley Review The Berkeley Review OrgaiUC ChemiStry Carbonyls and Alcohols Oxygen Containing Compounds Example 5.1 Whattype of alcohol is the following molecule? HiC CH„ HO- A. Primary alcohol B. Secondary alcohol C. Tertiary alcohol D. Phenol Solution The compound has the alcohol functional group attached to a carbon that is bonded to two other carbons. This is definedas a secondary alcohol, so the best answer is choice B. Alcohol Reactivity Alcohols are nucleophilic reagents in organic chemistry. They are not good nucleophiles in their protonated (neutral)state, but they can be deprotonated and converted into their anion (alkoxide) form under basic conditions. Because alkoxides (the deprotonated form of the alcohol) are strong bases, they are not the ideal nucleophile, but they are generally better than alcohols. Alcohol chemistry also involves oxidation into a carbonyl as we shall see later in this section. Alcohols are commonly formed from the reduction of carbonyls, which we shall also postpone for the moment. The common reactions to form and consume alcohols that do not involve carbonyl compounds center around nucleophilic substitution. Figure 5-2 shows nucleophilic substitution reactions that convert alkyl halides into alcohols. Figure 5-3 shows nucleophilic substitution reactions that convert alcohols into alkyl halides. Alkyl halides to alcohols R R OH + X h*%/ x ~2~~^ H*y H H R' R' \ 1. RCO," / „ . „^ TT R»';?-Br 2.0H-(ac,)» H°~V"R + + 2 H H R" R" „„t.^—X 1 • t,ii»»^— OH +HX Rv / acetone Rx / R' R' Figure 5-2 Copyright © by The BerkeleyReview 5 Exclusive MCAT Preparation OrCJ£UllG ChCHllStry Carbonyls and Alcohols Oxygen Containing Compounds Alcohols to alkyl halides O R « R /s^ Cl ,^-oh S ^—Cl Retention H^ H H R' R' PBr, OH Br-i Inversion r^; h H H R" R" OH ^L^. Br Racemization R^h r^; h K R' Figure 5-3 Spectroscopic Evidence for Alcohols Alcohols can be detected using either infrared or NMR spectroscopy. In IR spectra, hydroxyl groups present a distinct absorbance between 3200 and 3500 cm"1 that is medium in intensity and broad due to hydrogen bonding. In XHNMR spectra, hydroxyl groups present asignal between 1and 5ppm that is broaddue tohydrogen bonding, although the broadness varies with thesolvent. They have no definite 6-value (it varies with concentration and solvent). The peak slowly disappears with the addition of D2O to the NMR tube. The OH group does notcouple well, sowerarely consider splitting patterns foralcohols. Figure 5-4 shows the 1HNMR spectrum for 2-propanol in carbon tetrachloride solvent. Figure 5-5 shows the IR spectrum for 2-propanol obtained neat onsalt plates. H OH 6H H,C CH, 1H 1H 1 3.0 ppm 2.0 1.0 Figure 5-4 Copyright ©by TheBerkeley Review 6 The Berkeley Review Ur£J£UllC t/llCllllStry Carbonyls and Alcohols Oxygen Containing Compounds PTVl 1392 cm-' 1455 cm-1 & 1365 cm-' 2984 cm Figure 5-5 Aldehyde and Ketone Properties Because aldehydes and ketones do not form hydrogen bonds, they typically have boiling points only slightly higher than alkanes of equal mass. Because of the polarity of the carbonyl bond, they are slightly miscible in water. Aldehydes and ketones are aprotic, polar molecules that become less hydrophilic as their carbon chain length increases. The smaller aldehydes and ketones (three carbons or less) are generally water soluble but as the size of the alkyl group increases, their water solubility decreases. Table 5-2 shows the physical properties of several aldehydes and ketones, from which the effects of mass, branching, and positioning of the carbonyl group on the physical properties can be ascertained. Water IUPAC Name Boiling Melting Isomer Solubility (Common Name) Point Point (g/lOOmL) HCHO Methanal (Formaldehyde) -21°C -92°C High H3CCHO Ethanal (Acetaldehyde) 21°C -121°C Infinite H3CCH2CHO Propanal (Propionaldehyde) 49°C -81°C 16.3 H3C(CH2)2CHO Butanal (n-Butyraldehyde) 76°C -99°C 6.8 H3C(CH2)3CHO Pentanal 103°C -92°C 3.3 H3C(CH2)4CHO Hexanal 128°C -56°C 2.1 C6H5CHO Benzaldehyde 178°C -26°C 0.3 H3CCOCH3 Propanone (Acetone) 56°C -94°C Infinite H3CCOCH2CH3 Butanone (Ethyl methyl ketone) 80°C -86°C 25.6 H3CCO(CH2)2CH3 2-Pentanone 102°C -78°C 5.7 (H3CCH2)2CO 3-Pentanone 1018C -41'C 4.9 H3CCO(CH2)3CH3 2-Hexanone 128°C -55°C 1.6 H3CCH2CO(CH2)2CH3 3-Hexanone 124°C 1.3 H3CCOCH2CH(CH3)2 4-Methyl-2-Pentanone 119°C -85°C 1.9 C6Hi0O Cyclohexanone 156°C °C 2.2 C6H5COCH3 Acetophenone 202°C 21°C Insoluble Table 5-2 Copyright © by The Berkeley Review Exclusive MCAT Preparation OrCJcllllC l^IlCllllStry Carbonyls and Alcohols Oxygen Containing Compounds Example 5.2 What is the IUPACname for the following compound? OH r H O A. l-Aldo-4-pentanol B. 4-Hydroxypentanal C. 5-Oxo-2-pentanol D. 2-Hydroxypentaldehyde Solution The longest chain isfive carbons and the highest priority functional group is the aldehyde. The functional group with the most oxidized carbon receives the highest priority according toIUPAC convention. For naming aldehydes, the"e" is dropped from the alkane chain of thesamelengthand an "al" suffix is added. This makes the compound pentanal, which makes choice B correct. The OH is named hydroxy as a substituent. Aldehyde and Ketone Reactivity Aldehydes consist ofa carbonyl with a hydrogen bonded to the carbonyl carbon along with either an alkyl group or in the case of formaldehyde, a second hydrogen. Ketones consist of a carbonyl group with two alkyl substituents attached. The chemistry occurs primarily at the electrophilic carbonyl center. Aldehydes and ketones are reactive with most nucleophiles, but not by a traditional nucleophilic substitution mechanism. Once a nucleophile attacks a carbonyl carbon, it forms a four-ligand intermediate with a negative charge on oxygen known as a tetrahedral intermediate. This intermediate will be shown in the mechanism of many carbonyl reactions in this section. The chemistry of aldehydes is similar to the chemistry of ketones except that analdehyde can be oxidized into a carboxylic acid while ketones cannot be oxidized easily. Oxidation in carbonyl chemistry can be viewed as either the gain ofbonds to oxygen orthe loss of bonds to hydrogen. We shall thoroughly address carbonyl reactions throughout this section. Spectroscopic Evidence for Aldehydes and Ketones Aldehydes have infrared absorbances inthe 1720 cm"1 to1740 cm-1 range. They are unique in the IR from other carbonyls due to two medium C-H stretches around2700 cm-1 and 2900 cm-1. Ketones haveinfrared absorbances in the1710 cm-1 to 1725 cm-1 range. In *HNMR, aldehyde hydrogens are found between 9 and10 ppm, which makes aldehydes easy toidentify via *HNMR. Ketones and aldehydes each have alpha protons which fall in the 2.0 to 2.5 ppm range in !HNMR. Figure 5-6 shows the *HNMR spectrum for butanone in carbon tetrachloride solvent. Figure 5-7 shows the IR spectrum for butanal obtained neat on salt plates. Copyright ©by The Berkeley Review 8 The Berkeley Review

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