Notes for Organic Chemistry

Organic Chemistry 1: Nomenclatur IUPAC Naming Conventions Step 1: Find the parent chain, the longest carbon chain that contains the highest-priority functional group. Step 2: Number the chain in such a way that the highest-priority functional group receives the lowest possible number. Step 3: Name the substituents with a prefix. Multiples of the same type receive (di-, tri-, tetra-, etc.). Step 4: Assign a number to each substituent depending on the carbon to which it is bonded. Step 5: Alphabetize substituents and separate numbers from each other by commas and from words by hyphens. Hydrocarbons and Alcohols Carboxylic Acids & Derivatives Alkane: Hydrocarbon with no double or triple bonds. Alkane = C) H(,)-,) Naming: Alkanes are named according to the number of carbons present followed by the suffix –ane. Carboxylic Acid Alkene: Contains a double bond. Use suffix -ene. Carboxylic Acid: The highest priority functional group because it contains 3 bonds to oxygen. Alkyne: Contains a triple bond. Use suffix –yne. Alcohol: Contains a –OH group. Use suffix –ol or prefix hydroxy-. Alcohols have higher priority than double or triple bonds. Naming: Suffix –oic acid. Diol: Contains 2 hydroxyl groups. Geminal: If on same carbon Vicinal: If on adjacent carbons Ester Aldehydes and Ketones Amide Ester: Carboxylic Acid derivative where –OH is replaced with -OR. Aldehyde Amide: Replace the –OH group of a carboxylic acid with an amino group that may or may not be substituted. Ketone Carbonyl Group: C=O. Aldehydes and ketones both have a carbonyl group. Aldehyde: Carbonyl group on terminal C. Ketone: Carbonyl group on nonterminal C. Primary, Secondary, and Tertiary 1¡ Alcohols: Amines: 2¡ 3¡ Organic Chemistry 2: Isomer Structural Isomers Relative & Absolute Configuration ¥ Share only a molecular formula. ¥ Have different physical and chemical properties. Relative Configuration: Gives the stereochemistry of a compound in comparison to another compound. E.g. D and L. Absolute Configuration: Gives the stereochemistry of a compound without having to compare to other compounds. E.g. S and R. Stereoisomers Compounds with atoms connected in the same order but differing in 3D orientation. Chiral Center: Four different groups attached to a central carbon. 2n Rule: ! " #$%&$'()*+,$'-./-*0 #$%&$0/-*-%)0%1-*0 " 23 Cahn-Ingold-Prelog Priority is given by looking at atoms connected to Priority Rules: the chiral carbon or double-bonded carbons; whichever has the highest atomic # gets highest priority. (Z) and (E) for Alkenes: (Z): Highest priority on same side. (E): Highest priority on opposite sides. Conformational Isomers (R) and (S) for A stereocenter’s configuration is determined by Stereocenters: putting the lowest priority group in the back and drawing a circle from group 1-2-3. (R): Clockwise (S): Counterclockwise Anti Gauche Eclipsed Fischer Projection: Vertical lines go to back of page (dashes); horizontal lines come out of the page (wedges). Differ by rotation around a single (s) bond Cyclohexane Equatorial: In the plane of the molecule. Substituents: Axial: Sticking up/down from the molecule’s plane. Configurational Isomers Altering Fischer Switching 1 pair of substituents inverts the Projection: stereochemistry; switching 2 pairs retains stereochemistry. Rotating entire diagram 90¡ inverts the stereochemistry; rotating 180¡ retains stereochemistry. Enantiomers Enantiomers: Nonsuperimposable mirror images. Opposite stereochemistry at every chiral carbon. Same chemical and physical properties, except for rotation of plane polarized light. Optical Activity: The ability of a molecule to rotate plane-polarized light: d- or (+) = RIGHT, l- or (-) = LEFT. Racemic Mixture: 50:50 mixture of two enantiomers. Not optically active because the rotations cancel out. Meso Compounds: Have an internal plane of symmetry, will also be optically inactive because the two sides of the molecule cancel each other out. Diastereomers Diastereomers: Stereoisomers that are NOT mirror image. Cis-Trans: A subtype of diastereomers. They differ at some, but not all, chiral centers. Different chemical and physical properties. Organic Chemistry 3: Bondin Atomic Orbitals & Quantum Numbers Hybridization Quantum Numbers: Describe the size, shape, orientation, and number of atomic orbitals in an element sp3: 25% s character and 75% p character Tetrahedral geometry with 109.5¡ bond angles Quantum Number sp2: 33% s character and 67% p character Trigonal planar geometry with 120¡ bond angles Possible Values Name What it Labels n Principal e- energy level or shell number 1, 2, 3, … l Azimuthal 3D shape of orbital 0, 1, 2, …, n-1 ml Magnetic Orbital sub-type ms Spin Electron spin Notes Except for d-orbitals, the shell # matches the row of the periodic table 0 = s orbital 1 = p orbital 2 = d orbital 3 = f orbital 4 = g orbital Integers –l ® +l " " +#$, − # Maximum e- in terms of n = 2n2 Maximum e- in subshell = 4l + 2 Molecular Orbitals Bonding Orbitals: Created by head-to-head or tail-to-tail overlap of atomic orbitals of the same sign. ¯energy "stable Antibonding Orbitals: Created by head-to-head or tail-to-tail overlap of atomic orbitals of opposite signs. "energy ¯stable Single Bonds: 1 s bond, contains 2 electrons Double Bonds: 1 s + 1 p Pi bonds are created by sharing of electrons between two unhybridized p-orbitals that align side-by-side Triple Bonds: 1 s + 2 p Multiple bonds are less flexible than single bonds because rotation is not permitted in the presence of a p bond. Multiple bonds are shorter and stronger than single bonds, although individual p are weaker than s bonds sp: 50% s character and 50% p character Linear geometry with 180¡ bond angles Resonance: Describes the delocalization of electrons in molecules that have conjugated bonds Conjugation: Occurs when single and multiple bonds alternate, creating a system of unhybridized p orbitals down the backbone of the molecule through which p electrons can delocalize Organic Chemistry 4: Analyzing Organic Reaction Acids and Bases REDOX Reactions Lewis Acid: e- acceptor. Has vacant orbitals or + polarized atoms. Lewis Base: e- donor. Has a lone pair of e-, are often anions. Oxidation: Raises oxidation state. Assisted by oxidizing agents. Brønsted-Lowry Acid: Proton donor Oxidizing Agent: Accepts electrons and is reduced in the process. Brønsted-Lowry Base: Proton acceptor Amphoteric Can act as either acids or bases, depending on Molecules: reaction conditions. Ka: Acid dissociation constant. A measure of acidity. It is the equilibrium constant corresponding to the dissociation of an acid, HA, into a proton and its conjugate base. pKa: An indicator of acid strength. pKa decreases down the periodic table and increases with EN. !"# $ % &'()%*"# + a -carbon: A carbon adjacent to a carbonyl. a-hydrogen: Hydrogen connected to an a-carbon. SN 1 Oxidation Number: The charge an atom would have if all its bonds were completely ionic. Reduction: Lowers oxidation state. Assisted by reducing agents. Reducing Agent: Donates electrons and is oxidized in the process. Chemoselectivity Both nucleophile-electrophile and REDOX reactions tend to act at the highest-priority (most oxidized) functional group. One can make use of steric hindrance properties to selectively target functional groups that might not primarily react, or to protect functional groups. SN 2 E1 E2 Solvents Nucleophiles, Electrophiles and Leaving Groups Nucleophiles: “Nucleus-loving”. Contain lone pairs or p bonds. They have #EN and often carry a NEG charge. Amino groups are common organic nucleophiles. Polar Protic Polar Aprotic Polar Protic solvents Acetic Acid, H2O, ROH, NH3 Polar Aprotic solvents DMF, DMSO, Acetone, Ethyl Acetate Nucleophilicity: A kinetic property. The nucleophile’s strength. Factors that affect nucleophilicity include charge, EN, steric hindrance, and the solvent. Electrophiles: “Electron-loving”. Contain a + charge or are positively polarized. More positive compounds are more electrophilic. Leaving Group: Molecular fragments that retain the electrons after heterolysis. The best LG can stabilize additional charge through resonance or induction. Weak bases make good LG. SN1 Reactions: Unimolecular nucleophilic substitution. 2 steps. In the 1st step, the LG leaves, forming a carbocation. In the 2nd step, the nucleophile attacks the planar carbocation from either side, leading to a racemic mixture of products. ,-./ $ 0%12342.5-./6 SN2 Reactions: Bimolecular nucleophilic substitution. 1 concerted step. The nucleophile attacks at the same time as the LG leaves. The nucleophile must perform a backside attack, which leads to inversion of stereochemistry. (R) and (S) is also changed if the nucleophile and LG have the same priority level. SN2 prefers less-substituted carbons because steric hindrance inhibits the nucleophile from accessing the electrophilic substrate carbon. ,-./ $ 0%1738'/(!9:'/6%12342.5-./6 Substrate Polar Protic Polar Aprotic Strong Small Strong Bulky Solvent Solvent Base Base SN 2 SN 2 SN 2 SN 2 SN 2 SN 2 SN 2 E2 SN1 / E1 SN 2 E2 E2 SN1 / E1 SN1 / E1 E2 E2 Methyl Primary Secondary Tertiary Organic Chemistry 5: Alcohol Description & Properties Reactions of Alcohols Alcohols: Have the general form ROH and are named with the suffix –ol. If they are NOT the highest priority, they are given the prefix hydroxyPhenols: Benzene ring with –OH groups attached. Named for the relative position of the –OH groups: Primar y Can be oxidized to aldehydes only by pyridinium Alcohols: chlorochromate (PCC); they will be oxidized all the way to carboxylic acids by any stronger oxidizing agents Secondary Can be oxidized to ketones by any common oxidizing agent Alcohols: Alcohols can be converted to mesylates or tosylates to make them better leaving groups for nucleophilic substitution reactions Mesylates: Contain the functional group –SO3CH3 ortho meta Tosylates: Contain the functional group –SO3C6H4CH3 para ¥ ¥ ¥ Alcohols can hydrogen bond, raising their boiling and melting points Phenols are more acidic than other alcohols because the aromatic ring can delocalize the charge of the conjugate base Electron-donating groups like alkyl groups decrease acidity because they destabilize negative charges. EWG, such as EN atoms and aromatic rings, increase acidity because they stabilize negative charges Mesylate Tosylate Aldehydes or ketones can be protected by converting them into acetals or ketals Acetal: A 1¡ carbon with two –OR groups and an H atom Ketal: A 2¡ carbon with two –OR groups Reactions of Phenols Quinones: Synthesized through oxidation of phenols. Quinones are resonance-stabilized electrophiles. Vitamin K1 (phylloquinone) and Vitamin K2 (the menaquinones) are examples of biochemically relevant quinones Quinone Hydroxyquinones: Produced by oxidation of quinones, adding a variable number of hydroxyl gruops Ubiquinone: Also called coenzyme Q. Another biologically active quinone that acts as an electron acceptor in Complexes I, II, and III of the electron transport chain. It is reduced to ubiquinol Acetal Ketal Deprotection: The process of converting an acetal or ketal back to a carbonyl by catalytic acid Organic Chemistry 6: Aldehydes and Ketones I: Electrophilicity and Oxidation-Reductio Description and Properties Nucleophilic Addition Reactions Aldehydes: Are terminal functional groups containing a carbonyl bonded to at least one hydrogen. Nomenclature: suffix –al. In rings, they are indicated by the suffix –carbaldehyde. Ketones: Internal functional groups containing a carbonyl bonded to two alkyl chains. In nomenclature, they use the suffix –one and the prefix oxo- or keto-. When a nucleophile attacks and forms a bond with a carbonyl carbon, electrons in the p bond are pushed to the oxygen atom. If there is no good leaving group (aldehydes and ketones), the carbonyl will remain open and is protonated to form an alcohol. If there is a good leaving group (carboxylic acid and derivatives), the carbonyl will reform and kick off the leaving group. Hydration Rxns: Water adds to a carbonyl, forming a geminal diol. Carbonyl: A carbon-oxygen double bond. The reactivity of a carbonyl is dictated by the polarity of the double bond. The carbon has a d+ so it is electrophilic. Carbonyl containing compounds have a "BP than equivalent alkanes due to dipole interactions. Alcohols have "BP than carbonyls due to hydrogen bonding. Oxidation: Aldehydes and ketones are commonly produced by oxidation of primary and secondary alcohols, respectively. Weaker, anhydrous oxidizing agents like pyridinium chlorochromate (PCC) must be used for synthesizing aldehydes, or the reaction will continue oxidizing to a carboxylic acid. 1¡ Alcohol Aldehyde or Ketone Gem-diol Aldehyde + Alcohol: When one equivalent of alcohol reacts with an aldehyde, a hemiacetal is formed. When the same rxn occurs with a ketone, a hemiketal is formed. When another equivalent of alcohol reacts with a hemiacetal (via nucleophilic substitution), an acetal is formed. When the same reaction occurs with a hemiketal, a ketal is formed. Aldehyde Oxidation-Reduction Reactions Aldehydes: Aldehydes can be oxidized to carboxylic acids using an oxidizing agent like KMnO4, CrO3, Ag2O, or H2O2. They can be reduced to primary alcohols via hydride reagents (LiAlH4, NaBH 4). Ketones: Ketones cannot be further oxidized, but can be reduced to secondary alcohols using the same hydride reagents. Nitrogen + Carbonyl: Nitrogen and nitrogen derivatives react with carbonyls to form imines, oximes, hydrazones, and semicarbazones. Imines can tautomerize to form enamines. Common Oxidizing / Reducing Agents Oxidizing Agent PCC Reactant Product 1¡ alcohol Aldehyde 1¡ Amine KMnO4 or H2Cr2O4 Aldehyde or Ketone Imine Ketone 2¡ alcohol 1¡ alcohol Carboxylic Acid Reducing Agent 2¡ alcohol Ketone Reactant Product Imine NaBH4 Aldehydes / Ketones 1¡ alcohol 2¡ alcohol LiAlH4 (LAH) Aldehydes Ketones 1¡ alcohol 2¡ alcohol Carboxylic Acid Ester 1¡ alcohol 2¡ alcohol Enamine HCN + Carbonyl: Hydrogen cyanide reacts with carbonyls to form cyanohydrins. Organic Chemistry 7: Aldehydes and Ketones II: Enolate General Principles a -carbon: The carbon adjacent to the carbonyl is the a-carbon. The hydrogens attached to the a-carbon are the a-hydrogens. Aldol Condensation Starts with an aldol addition to create an aldol and create a new C-C bond Then it undergoes a dehydration to give a conjugated enone (α,βunsaturated carbonyl) Aldol: Contains both aldehyde and an alcohol. “Ald – ol” a-hydrogens: Relatively acidic and can be removed by a strong base. The e- withdrawing O of the carbonyl weakens the C-H bonds on a-hydrogens. The enolate resulting from deprotonation can be stabilized by resonance with the carbonyl. Ketones: Ketones are less reactive toward nucleophiles because of steric hindrance and a-carbanion de-stabilization. The presence of an additional alkyl group crowds the transition step and increases energy. The alkyl group also donates edensity to the carbanion, making it less stable. Enolate Chemistry Keto / Enol: Aldehydes and ketones exist in both keto form (more common) and enol form (less common). Tautomers: Isomers that can be interconverted by moving a hydrogen and a double bond. Keto / Enol are tautomers. Michael Addition: An enolate attacks an a,b-unsaturated carbonyl, creating a bond. Kinetic Enolate: Favored by fast, irreversible reactions at LOW TEMP, with strong, sterically hindered bases. Thermodynamic Favored by slower, reversible reactions at HIGH TEMP Enolate: with weaker, smaller bases. Enamines: Tautomers of imines. Like enols, enamines are the less common tautomer. Aldol The nucleophile is the enolate formed from the Nucleophile: deprotonation of the a-carbon. Aldol The electrophile is the aldehyde or ketone in the form Electrophile: of the keto tautomer. Dehydration: After the aldol is formed, a dehydration reaction (loss of water molecule) occurs. This results in an a,bunsaturated carbonyl. Retro-Aldol Reverse of aldol reactions. Catalyzed by heat and base. Reactions: Bond between a- and b-carbon is cleaved. Organic Chemistry 8: Carboxylic Acid Description and Properties Carboxylic acids contain a carbonyl and a hydroxyl group connected to the same carbon. They are always terminal groups. Nomenclature: Suffix –oic acid. Salts are named with the suffix –oate, and dicarboxylic acids are –dioic acids Physical Carboxylic acids are polar and hydrogen bond well, Properties: resulting in high BP. They often exist as dimers in solution. Acidity: The acidity of a carb acid is enhanced by the resonance between its oxygen atoms. The acidity can be further enhanced by substituents that are electron-withdrawing, and decreased by substituents that are electron-donating b-dicarboxylic Like other 1,3-dicarbonyl compounds, they have an aAcids: hydrogen that is also highly acidic a-proton is the most acidic due to resonance Carboxylic Acid Synthesis via Oxidation Reactions of Carboxylic Acids Oxidation: Carboxylic acids can be made by the oxidation of 1¡ alcohols or aldehydes or the oxidation of 1¡ or 2¡ alkyl groups using an oxidizing agent like KMnO4, Na2Cr2O7, K2Cr2O7, or CrO3. Nucleophilic Acyl A common reaction in carboxylic acids. Nucleophile Substitution: attacks the electrophilic carbonyl carbon, opening the carbonyl and forming a tetrahedral intermediate. The carbonyl reforms, kicking off the L.G. Nucleophiles: Ammonia / Amine: Forms an amide. Amides are given the suffix –amide. Cyclic amides are called lactams. Alcohol: Forms an ester. Esters are given the suffix – oate. Cyclic esters are called lactones. Carboxylic Acid: Forms an anhydride. Both linear and cyclic anhydrides are given the suffix anyhydride. Reduction: Carboxylic acids can be reduced to a 1¡ alcohol with a strong reducing agent like LiAlH4. Aldehyde intermediates are formed, but are also reduced to 1¡ alcohols. NaBH4 is not strong enough to reduce a carboxylic acid Decarboxylation: b-dicarboxylic acids and other b-keto acids can undergo spontaneous decarboxylation when heated, losing a carbon as CO2. This reaction proceeds via a six-membered cyclic intermediate Saponification: Mixing long-chain carboxylic acids (fatty acids) with a strong base results in the formation of a salt we call soap. Soaps contain a hydrophilic carboxylate head and hydrophobic alkyl chain tail. They organize in hydrophilic environments to form micelles. A micelle dissolves nonpolar organic molecules in its interior, and can be solvated with water due to its exterior shell of hydrophilic groups. Reduction of Carboxylic Acid Yields a 1 ¡ Alcohol Micelle: Polar heads, non-polar tails. The non-polar tails dissolve non-polar molecules such as grease Amide Synthesis Nucleophilic Acyl Substitution Anhydride Synthesis Acid Halide Synthesis Ester Synthesis Organic Chemistry 9: Carboxylic Acid Derivative Amides, Esters, and Anhydrides Reactivity Principles Amides: The condensation product of carboxylic acid and ammonia or an amine. Amides are given the suffix –amide. The alkyl groups on a substituted amide are written at the beginning of the name with the prefix N-. Cyclic amides are called lactams, named with the Greek letter of the carbon forming the bond with the N. N,N-Dimethylpropanamide b-Lactam Esters: The condensation products of carboxylic acids with alcohols, i.e., a Fischer Esterification. Esters are given the suffix –oate. The esterifying group is written as a substituent, without a number. Cyclic esters are called lactones, named by the number of carbons in the ring and the Greek letter of the carbon forming the bond with the oxygen. Triacylglycerols include three ester bonds between glycerol and fatty acids. Isopropyl butanoate b-Propiolactone Anhydrides: The condensation dimers of carboxylic acids. Symmetric anhydrides are named for the parent carb acid, followed by anhydride. Asymmetric anhydrides are named by listing the parent carb acids alphabetically, followed by anhydride. Some cyclic anhydrides can be synthesized by heating dioic acids. Five- or six-membered rings are generally stable. Ethanoic propanoic anhydride Ethanoic anhydride In Nu- substitution reactions, reactivity is: acid chloride > anhydrides > esters > amides > carboxylate Steric Hindrance: Describes when a reaction cannot proceed (or significantly slows) because substituents crowd the reactive site. Protecting groups, such as acetals, can be used to increase steric hindrance or otherwise decrease the reactivity of a particular portion of a molecule Induction: Refers to uneven distribution of charge across a s bond because of differences in EN. The more EN groups in a carbonyl-containing compound, the greater its reactivity Conjugation: Refers to the presence of alternating single and multiple bonds, which creates delocalized p electron clouds above and below the plane of the molecule. Electrons experience resonance through the unhybridized p-orbitals, increasing stability. Conjugated carbonyl-containing compounds are more reactive because they can stabilize their transition states. Conjugation in Benzene Ring Strain: Increased strain in a molecule can make it more reactive. b-lactams are prone to hydrolysis because they have significant ring strain. Ring strain is due to torsional strain from eclipsing interactions and angle strain from compression bond angles below 109.5¡ Succinic anhydride Fischer Esterification Nucleophilic Acyl Substitution Reactions All carboxylic acid derivatives can undergo nucleophilic substitution reactions. The rates at which they do so is determined by their relative reactivities. Cleavage: Anhydrides can be cleaved by the addition of a nucleophile. Addition of ammonia or an amine results in an amide and a carboxylic acid. Addition of an alcohol results in an ester and a carboxylic acid. Addition of water results in two carboxylic acids. Synthesis of an Anhydride via Carboxylic Acid Condensation Transesterification: The exchange of one esterifying group for another on an ester. The attacking nucleophile is an alcohol. Amides: Can be hydrolyzed to carboxylic acids under strongly acidic or basic conditions. The attacking nucleophile is water or the hydroxide anion. Organic Chemistry 10: Nitrogen- and Phosphorus-Containing Compound Amino Acids, Peptides, and Proteins Amino Acid: The a-carbon of an amino acid is attached to four groups: an amino group, a carboxyl group, a hydrogen atom, and an R group. It is chiral in all amino acids except glycine. All amino acids in eukaryotes are L-amino acids. They all have (S) stereochemistry except cysteine, which is (R). Amphoteric: Amino acids are amphoteric, meaning they can act as acids or bases. Amino acids get their acidic characteristics from carboxylic acids and their basic characteristics from amino groups. In neutral solution, amino acids tend to exist as zwitterions (dipolar ions). Aliphatic: Non-aromatic. Side chain contains only C and H. Gly, Ala, Val, Leu, Ile, Pro. Met can also be considered aliphatic. Peptide Bonds: Form by condensation reactions and can be cleaved hydrolytically. Resonance of peptide bonds restricts motion about the C-N bond, which takes on partial double bond character. A strong acid or base is needed to cleave a peptide bond. Formed when the N-terminus of an AA nucleophilically attacks the C-terminus of another AA. Phosphorus-Containing Compounds Phosphoric Acid: Sometimes referred to as a phosphate group or inorganic phosphate, denoted Pi. At physiological pH, inorganic phosphate includes molecules of both hydrogen phosphate (HPO42-) and dihydrogen phosphate (H2PO4-). Phosphoric Acid Contains 3 hydrogens, each with a unique pKa. The Structure: wide variety in pKa values allows phosphoric acid to act as a buffer over a large range of pH values. Phosphodiester Phosphorus is found in the backbone of DNA, which Bonds: uses phosphodiester bonds. In forming these bonds, a pyrophosphate (PPi, P2O74-) is released. Pyrophosphate can then be hydrolyzed to two inorganic phosphates. Phosphate bonds are high energy because of large negative charges in adjacent phosphate groups and resonance stabilization of phosphates. Organic Carbon containing compounds that also have phosphate Phosphates: groups. The most notable examples are nucleotide triphosphates (such as ATP or GTP) and DNA. Polypeptides: Made up of multiple amino acids linked by peptide bonds. Proteins are large, folded, functional polypeptides. Synthesis o -Amino Acids Biologically, amino acids are synthesized in many ways. In the lab, certain standardized mechanisms are used. Strecker Generates an amino acid from an aldehyde. An Synthesis: aldeyhyde is mixed with ammonium chloride (NH4Cl) and potassium cyanide. The ammonia attacks the carbonyl carbon, generating an imine. The imine is then attacked by the cyanide, generating an aminonitrile. The aminonitrile is hydrolyzed by two equivalents of water, generating an amino acid. Gabriel Synthesis: Generates an amino acid from potassium phthalimide, diethyl bromomalonate, and an alkyl halide. Phthalimide attacks the diethyl bromomalonate, generating a phthalimidomalonic ester. The phthalimidomalonic ester attacks an alkyl halide, adding an alkyl group to the ester. The product is hydrolyzed, creating phthalic acid (with two carboxyl groups) and converting the esters into carboxylic acids. One carboxylic acid of the resulting 1,3-dicarbonyl is removed by decarboxylation. Gabriel Synthesis of an Amino Acid Strecker Synthesis of an Amino Acid Organic Chemistry 11: Spectroscop Infrared Spectroscopy Nuclear Magnetic Resonance Spectroscopy Measures absorption of infrared light, which causes molecular vibration (stretching, bending, twisting, and folding). Plotted as % transmittance vs. ! wavenumber ( ). l Peaks to Know for MCAT: Bond Range (cm-1) Peak Type N-H 3300 Sharp O-H 3000 - 3300 Broad C O, C N 1900 – 2200 Medium C=O 1750 Sharp C=C 1600 – 1680 Weak IR Spectrum of Cyclohexanol NMR spectroscopy measures alignment of nuclear spin with an applied magnetic field, which depends on the magnetic environment of the nucleus itself. It is useful for determining the structure (connectivity) of a compound, including functional groups. Generally plotted as frequency vs. absorption energy. They are standardized by using chemical shift (d), measured in parts per million (ppm) of spectrophotometer frequency. TMS: NMR spectra are calibrated using tetramethylsilane (TMS), which has a chemical shift of 0 ppm Integration: Area under the curve. Proportional to the number of protons contained under the peak. Deshielding: Occurs when electron-withdrawing groups pull electron density away from the proton’s nucleus, allowing it to be more easily affected by the magnetic field. Deshielding moves a peak further downfield Downfield: LEFT. Deshielded by EWG or EN atom nearby. Upfield: RIGHT. More shielded, by EDG or less EN atom nearby. IR Spectrum of Benzaldehyde Spin-Spin When hydrogens are on adjacent atoms, they interfere with Coupling: each other’s magnetic environment, causing spin-spin coupling (splitting). A proton’s (or a group of protons’) peak is split into n+ 1 subpeaks, where n is the number of protons that are three bonds away from the proton of interest. Splitting patterns include doublets, triplets, and multiplets. 1H-NMR Shifts to Know for the MCAT IR Spectrum of Cyclohexylamine Mass Spectrometry Used to determine the molecular weight and aid in determining molecular structure. The charged molecule collides with an electron, resulting in the ejection of an electron from the molecule, making it a radical. Base Peak: Tallest peak (not always the intact molecule) Molecular Ion Peak: Peak that represents the molecule. Ultraviolet Spectroscopy UV spectroscopy is most useful for studying compounds containing double bonds and/or heteroatoms with lone pairs that create conjugated systems. Measures the absorption of UV light, which causes movement of electrons between molecular orbitals. UV spectra are generally plotted as percent transmittance or absorbance vs. Wavelength. M+1 Peak: Relative abundance of 13C. Found in relative abundance of 1.1%. So, if M+1 has an m/z value of 4.4, that means there are 4 carbons. 4.4/1.1 = 4. M+2 Peak: Relative abundance of either 81Br or 37Cl. Br has a 1:1 ratio relative to the M peak. Cl has a 3:1 ratio relative to the M peak. HOMO & LUMO: To appear on a UV spectrum, a molecule must have a small enough energy difference between its HOMO and LUMO to permit an electron to move from one orbital to the other. The smaller the difference between HOMO and LUMO, the longer the wavelengths a molecule can absorb. Mass Spec of Bromoethane. M+ has similar intensity as M+2. Organic Chemistry 12: Separations and Purification Solubility-Based Methods Extraction: Combines two immiscible liquids, one of which easily dissolves the compound of interest. Nonpolar Layer: Organic layer, dissolves nonpolar compounds. Polar Layer: Aqueous (water) layer. Dissolves compounds with hydrogen bonding or polarity. Wash: The reverse of an extraction. A small amount of solvent that dissolves impurities is run over the compound of interest. Filtration: Isolates a solid (residue) from a liquid (filtrate) Gravity Filtration: Use when the product of interest is in the filtrate. Hot solvent is used to maintain solubility. Vacuum Filtration: Used when the product of interest is the solid. A vacuum is connected to the flask to pull the solvent through more quickly. Recrystallization: The product is dissolved in a minimum amount of hot solvent. If the impurities are more soluble, the crystals will reform while the flask cools, excluding the impurities. Chromatography * See appendix for detailed information Separates two or more molecules from a mixture. Includes liquid chromatography, gas chromatography, size-exclusion chromatography, ion-exchange chromatography, affinity chromatography, and thin-layer chromatography. Distillation Distillation: Separates liquids according to differences in their boiling points. The liquid with the lowest BP vaporizes first and is collected as the distillate. Simple Can be used if the boiling points are under 150¡C and are at Distillation: least 25¡C apart. Vacuum Should be used if the boiling points are over 150¡C to Distillation: prevent degradation of the product. The vacuum lowers the air pressure, which decreases the temp the liquid must reach in order to boil. Fractional Should be used if the boiling points are less than 25¡C apart Distillation: because it allows more refined separation of liquids by BP. Most Experiments Organic on top Aqueous on bottom Extraction: Polar solutes dissolve in the aqueous layer. Non-polar solutes dissolve in the organic layer.