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chapter9 - Happy Halloween! 1 9. Stereochemistry Based on...

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Unformatted text preview: Happy Halloween! 1 9. Stereochemistry Based on McMurry's Organic Chemistry, 7th edition 2007 Nobel Prize in Chemistry The 2007 Nobel Prize in chemistry has been awarded to Gerhard Ertl, not for a singular result or discovery, but for his body of work that founded modern surface chemistry. Currently a professor emeritus in the physical chemistry department at the FritzHaber-Institut der Max-Planck-Gesellschaft, he spent the majority of his career studying reactions on surfaces. Working with experiments and processes developed for the semiconductor industry in the 1960s, Prof. Ertl "founded an experimental school of thought by showing how reliable results can be attained in this difficult area of research." 3 Chemistry Nobel Prize Winners that I have met. Seaborgium 106 Rudolf Mssbauer-1961 Elias Corey - 1990 Physics Mssbauer Organic Chemistry Spectroscopy Organic Synthesis Glen Seaborg 1951 Donald Cram 1987 Herbert C. Brown-1979 Physical Chemistry Organic Chemistry Organic Chemistry Transuranium Elements Stereochemistry Boron Reagents Who is Next? Gerhard Erdl - 1993 Physical Chemistry Surface Chemistry Thomas Chec-1989 Biochemistry Catalytic RNA Robert Curl -1996 Analytical Chem. Fullerene Discov. Kerry Mullis - 1993 Biochemistry DNA PCR Reaction 4 Don't Plan on Winning the Nobel Prize Herbert C. Brown-1979 Organic Chemistry Boron Reagents, including the hydroboration reaction. Commencement Speaker at Princeton Asked by the President of the school to tell the students how they could win the Nobel Prize. He told the student body not to worry about it, because none of them was likely to win the Nobel Prize. Instead make an important contribution to your field. If the Nobel Prize comes along then great, but don't plan on it. 5 Challenges in Winning the Nobel Prize Kerry Mullis - 1993 Biochemistry DNA PCR Reaction Politics Proprietary Property of Company (Most winners come from academia Dr. Mullis is an exception.) Who made the discovery first? 6 Stereochemistry Some objects are not the Do a poll on how many left handed students in the class. same as their mirror images (technically, they have no plane of symmetry) A right-hand glove is different than a left-hand glove. The property is commonly called "handedness" Organic molecules (including many drugs) have handedness that results from substitution patterns on sp3 hybridized carbon Everything has a mirror image, except? 7 Everything, except Vampires have a mirror image. 8 Stereochemistry Some objects are not the same as their mirror images (technically, they have no plane of symmetry) A right-hand glove is different than a lefthand glove. The property is commonly called "handedness" Organic molecules (including many drugs) have handedness that results from substitution patterns on sp3 hybridized carbon Use Latin Words sinister rectus 9 Why this Chapter? Handedness is important in organic and biochemistry Molecular handedness makes possible specific interactions between enzymes and substrates Like putting a left hand into a left handed glove, or a right hand into a right handed glove. Animals only use left handed amino acids to make protein and right handed sugars for energy. 10 9.1 Enantiomers and the Tetrahedral Carbon Enantiomers are molecules that are not the same as their mirror image They are the "same" if the positions of the atoms can coincide on a one-to-one basis (we test if they are superimposable, which is imaginary) This is illustrated by enantiomers of lactic acid compound No matter how you orient the two molecules, you cannot superimpose them. mirror image Enantiomers have identical properties, such as m.p., b.p., vapor pressure, and in most cases participate in identical chemical reactions. 11 Examples of Enantiomers Molecules that have one carbon with 4 different substituents have a nonsuperimposable mirror image enantiomer Build molecular models to see this Showed Models in Lecture! Also used Spartan to illustrate this concept. 12 9.2 The Reason for Handedness: Chirality Molecules that are not superimposable with their mirror images are chiral (have handedness) A plane of symmetry divides an entire molecule into two pieces that are exact mirror images A molecule with a plane of symmetry is the same as its mirror image and is said to be achiral (See Figure 9.4 for examples) 13 Chirality If an object has a plane of symmetry it is necessarily the same as its mirror image The lack of a plane of symmetry is called "handedness", chirality Hands, gloves are prime examples of chiral object They have a "left" and a "right" version 14 Plane of Symmetry The plane has the same thing on both sides for the flask There is no mirror plane for a hand 15 Chirality Centers A point in a molecule where four different groups (or atoms) are attached to carbon is called a chirality center There are two nonsuperimposable ways that 4 different different groups (or atoms) can be attached to one carbon atom If two groups are the same, then there is only one way A chiral molecule usually has at least one chirality center 16 Fisher Convention of Drawing Stereoisomers Yo m see th ch cen illu u ay e iral ters stratedu gan o e o th th m o s sin y n f ese ree eth d M RR IR O H C l O H B r B r O H H C l C l O H H B r B r O H M RR IR O H C l C l H C B r O H M RR IR O etc. F e P je n ish r ro ctio Hrizo ta lin s a co in o t o n l e re m g u o th p n o th p p r a d f e la e f e a e n th d sh dlin s a g in b ck e a e e re o g a b h dth p p r. e in e a e Tis is wh t yo sh u e visio h a u o ld n n wh nyo lo k a aF e p je n e u o t ish r ro ctio . F e P je nm y a ish r ro ctio a lso b writte liketh e n is. Enantiomers : Nonsuperimposible mirror images. Chiral Center: has four different groups attached to the central carbon, i.e. No plane of symmetry. 17 Sample Problems How many chiral carbon centers in the following molecules? Would it's mirror image be an enantiomer? Is there a plane of symmetry? C3 H H H C3 H H H H O H C l O H C3 H O H C3 H O H C3 H O H C3 H O H H C3C2 HH C C2C3 HH O H Are the following molecules enantiomers or are they identical compounds? B r C3 H C N H H C3 H 18 C N B r Chirality Centers in Chiral Molecules Groups are considered "different" if there is any structural variation (if the groups could not be superimposed if detached, they are different) In cyclic molecules, we compare by following in each direction in a ring SPARTAN ILLUSTRATION DONE IN CLASS 19 9.3 Optical Activity Light restricted to pass through a plane is plane- polarized Plane-polarized light that passes through solutions of achiral compounds remains in that plane Solutions of chiral compounds rotate plane-polarized light and the molecules are said to be optically active Phenomenon discovered by Jean-Baptiste Biot in the early 19th century 20 Optical Activity Light passes through a plane polarizer Plane polarized light is rotated in solutions of optically active compounds Measured with polarimeter Rotation, in degrees, is Clockwise rotation is called dextrorotatory Anti-clockwise is levorotatory 21 Housekeeping Items CHEMISTRY AS A CAREER AND TOUR OF RESEARCH LABS OCTOBER 25 at 12:00 Noon, Coolbaugh 209, Pizza + Soda - CAREER PATHS AND OPORTUNITIES - POSTEDUCATIONAL OPORTUNITIES, Ph.D, MED. SCHOOL, ETC. - SALARIES SCIENCE SHOW NOVEMBER 25 (3-4 Middle Schools) ACS Student Affiliates help prepare demonstrations. Joe Stranahan will help with preparation. 22 Measurement of Optical Rotation A polarimeter measures the rotation of plane- polarized that has passed through a solution The source passes through a polarizer and then is detected at a second polarizer The angle between the entrance and exit planes is the optical rotation. Ocillating electric field 23 Specific Rotation To have a basis for comparison, define specific rotation, D for an optically active compound D = observed rotation/(pathlength x concentration) = /(l x C) = degrees/(dm x g/mL) Specific rotation is that observed for 1 g/mL in solution in cell with a 10 cm path using light from sodium metal vapor (589 nm) [ ]D = / (l X C) Where [ ]D = specific rotation = observed rotation in degrees l = path length (cell thickness) C = concentration of compound in the cell 24 Specific Rotation and Molecules Characteristic property of a compound that is optically active the compound must be chiral opposite in sign The specific rotation of the enantiomer is equal in magnitude but 25 9.4 Pasteur's Discovery of Enantiomers Louis Pasteur discovered that sodium ammonium salts of tartaric acid crystallize into right handed and left handed forms The optical rotations of equal concentrations of these forms have opposite optical rotations The solutions contain mirror image isomers, called enantiomers and they crystallized in distinctly different shapes such an event is rare 26 9.5 Sequence Rules for Specification of Configuration A general method applies to the configuration at each chirality center (instead of to the whole molecule) The configuration is specified by the relative positions of all the groups with respect to each other at the chirality center The groups are ranked in an established priority sequence and compared The relationship of the groups in priority order in space determines the label applied to the configuration, according to a rule 27 Sequence Rules (IUPAC) Rule 1: Assign each group priority according to the Cahn Ingold-Prelog scheme With the lowest priority group pointing away, look at remaining 3 groups in a plane Clockwise is designated R (from Latin for "right") Counterclockwise is designated S (from Latin word for "left") 28 Use the same Cahn-Ingold-Prelog rules we used for E and Z nomenclature. Rule 2: If decision can't be reached by ranking the first atoms in the substituents, look at the second, third, or fourth atoms until difference is found There is no correlation between d (+) or l (-) and R or S. The d and l designate the rotation of light, and the R and S designate the three dimensional stereochemistry. clockwise counter clockwise 29 Rule 3: Multiple-bonded atoms are equivalent to the same number of single-bonded atoms 30 9.6 Diastereomers Molecules with more than one chirality center have mirror image stereoisomers that are enantiomers In addition they can have stereoisomeric forms that are not mirror images, called diastereomers 31 32 Summary of Stereoismers Enantiomers = They are non-superimposable mirror images and optically active. They have idential chemical and physical properties, such as m.p., b.p., solubility, etc., which makes them very difficult to separate from each other. Meso = superimposable mirror images (same compound) and optically inactive They do have chirals centers, but they also have a plane of symmetry through the molecule. Diasteriomers = non-superimposable and non-mirror images. They have chiral centers, but are not mirror images. They may or may not be optically active. They have different physical properties and are much easier to separate from each other. 33 R & S Configuration of a Chiral Center C3 H H O O H C C H H O B r N2 H C3 H S E E C E IS R R L S T RO HM T Y UE : 1 Id tify ch cen . en iral ter. 2. G p rity toeachg u u gC n g ld relo R les ive rio ro p sin ah -In o -P g u 3. O t m lecu withlo rien o le west p rity g u inb rio ro p ack 4. D eterm e th Ro Sco fig ratio o ch cen in e r n u n f iral ter 34 R & S Configuration of a Chiral Center C3 H H O O H C C H N TAC IR L O HA CN R E TE H O B r C IR L HA CN R E TE Give Cahn-Ingold-Prelog priority to groups attached to chiral center. N2 H C3 H 35 R & S Configuration of a Chiral Center 3 N2 H 2H O B r 1 L BLB AE Y P IO ITY RR C34 H 3 N2 H H O B1 r IDN Y3D E ITF S RO HM TR TE E C E IS Y C3 4 H 1 B r 3 N2 H 4 1 B r 3 N2 H 4 2 C3 H O H 2 C3 H O H 2 R TA M LC L O TE OE U E S Y UC NS H O O A IG T D W TH C IR L ON EHA C R O A MTOTH A B N TO E G O PO L W S R U F O ET P IO ITY RR D E TH N M E OS E U BR S Q E C G INA E UN E O C O K IS O C U TE L CW E R ON R C O K IS F S IO ? L CW E A H N C O K IS = R(R s) L CW E ectu C U TE C O K IS = S(S ister) ON R L CW E in Used Spartan model to illustrate this during lecture Compound Name: 1S-1-bromo-1-amino-1-ethanol 36 R & S Configuration of a Chiral Center DEMONSTRATED CONCEPTS IN LECTURE USING SPARTAN iodine iodine DO SPARTAN DEMO!!! Chiral carbon Nonchiral carbon oxygen chlorine Has a plane of symmetry through carbon center chlorine Has no plane of symmetry through carbon center 37 What is the R or S configuration of the following molecules? C N H C3 H C=C2 H H H C3 H C2C3 HH B r H CO H N2 H H O C3 H C2H O 38 B r Do this one on the board. O H Students do these. What is the R or S configuration of the following molecules? - SOLUTION 4 2 C N H 3 C3 H C=C2 H H H C3 H C2C3 HH B r H CO H N2 H H O C3 H C2H O O H 1 B r 4 H 2 C N C3 H 3 4 2 1 B r RT T OA E M LC L OEUE 1 C=C2 H H H 3 C3 H C2C3 HH B r 1 clockwise C N H4 Look down bond from chiral atom to group of lowest priority H R C3 3 H H 1 C=C2 H4 C3 R C2C3 H HH 3 2 clockwise RT T OA E M LC L OEUE 2 1 1 B Counter clockwise r B r 4 2 4 RT T OA E H H O H M LC L OEUE H S CO O H CO H 3 2 3 2 N2 H RT T OA E H O C3 H M LC L OEUE 1 CH 4 O 2 Group with lowest priority goes behind the plane of the paper and all other groups are out in front of plane of paper. The chiral atom is in the plane of paper. 21 N H 2 4 C3 H 3 H2C R O O H 3 3 S 21 Counter clockwise These groups are numbered correctly. Oops! Corrections in RED 39 SAMPLE PROBLEMS FROM THE TEXTBOOK WORKED ON BOARD Assign R or S configuration to each chirality center in the following molecules. OH H Cl HO CH3 H OH CH3 Draw a tetrahedral representation of the following molecule. (S)-2-chlorobutane 40 9.7 Meso Compounds Tartaric acid has two chirality centers and two diastereomeric forms One form is chiral and the other is achiral, but both have two chirality centers An achiral compound with chirality centers is called a meso compound it has a plane of symmetry The two structures on the right in the figure are identical so the compound (2R, 3S) is achiral S optically active enantiomers optically inactive meso R One half of the molecule is a mirror image of the other half, thus the molecule is optically inactive. 41 nonsuperimposable superimposable HOUSEKEEPING ITEMS Exam November 1st at 7:30 pm in CO209. Same format as Exam #1. Exam will cover Chapters 6, 7, 8, and 9. Help Session? Friday at 5:00 pm? Monday at 6:00 pm? Tuesday (I am not available.) Wednesday at 6:00 pm? 42 Housekeeping Items Organic Lab, October 25, 30 Greener Bromination of an Alkene Organic Lab, November 1, 6 Spartan Lab #2 on Stereochemistry Meet in CTLM B60 Spartan Lab 43 9.8 Racemic Mixtures and The Resolution of Enantiomers A 50:50 mixture of two chiral compounds that are mirror images does not rotate light called a racemic mixture (named for "racemic acid" that was the double salt of (+) and (-) tartaric acid The pure compounds need to be separated or resolved from the mixture (called a racemate) To separate components of a racemate (reversibly) we make a derivative of each with a chiral substance that is free of its enantiomer (resolving agent) This gives diastereomers that are separated by their differing solubility The resolving agent is then removed Enantiomers are very difficult to separate from each other. Diastereomers are more easily separated from each other. 44 Enantiomers are very difficult to separate from each other. achiral reagent Products are still enantiomers and still very difficult to separate. 45 Solution: Convert enantiomers into diastereomers. Nonsuperimposable mirror images R Non-mirror images chiral reagent Enantiomers have identical physical properities and are very difficult to separate from each other. Diastereomers have different physical properities and are easy to separate from each other. 46 9.9 A Review of Isomerism The flowchart summarizes the types of isomers we have seen 1. 2. 3. Structural or skeletal Functional Positional 47 Constitutional Isomers Different order of connections gives different carbon backbone and/or different functional groups Structural isomers Functional isomers Positional isomers 48 Stereoisomers Same connections, different spatial arrangement of atoms Enantiomers (nonsuperimposable mirror images) Diastereomers (all other stereoisomers) Includes cis, trans and configurational 49 Examples of Stereoisomers C3 H CB Hr CB Hr C3 H Recommended Procedure: 1. Identify the chiral centers? 2. Draw the Fisher projections and mirror images 3. Is there a plane of symmetry in the molecules 4. What is the R and S configuration of each chiral center? 5. Are the mirror images superimposable? 6. Are the mirror images entantiomers, meso, or diasteriomers? 7. What is the name of each compound? Generic Molecular Formula 50 Examples of Stereoisomers C3 H Hr * CB Hr * CB C3 H Recommended Procedure: 1. Identify the chiral centers? 2. Draw the Fisher projections and mirror images 3. Is there a plane of symmetry in the molecules 4. What is the R and S configuration of each chiral center? 5. Are the mirror images superimposable? 6. Are the mirror images entantiomers, meso, or diasteriomers? 7. What is the name of each compound? Generic Molecular Formula 51 Examples of Stereoisomers M r irro C3 H CB Hr CB Hr C3 H H B r C3 H C3 H B r H B r H C3 H C3 H H B r H H C3 H C3 H B r B r B r B r C3 H M r irro C3 H H H Gn ric ee Frm la o u Recommended Procedure: 1. Identify the chiral centers? 2. Draw the Fisher projections and mirror images 3. Is there a plane of symmetry in the molecules 4. What is the R and S configuration of each chiral center? 5. Are the mirror images superimposable? 6. Are the mirror images entantiomers, meso, or diasteriomers? 7. What is the name of each compound? 52 Examples of Stereoisomers M r irro C3 H CB Hr CB Hr C3 H C3 H H S B r S M r irro C3 H C3 H H B r H H C3 H B r B r B r B r C3 H C3 H H H Plane of symmetry B r H B r H R R C3 H C3 H Gn ric ee Frm la o u Recommended Procedure: 1. Identify the chiral centers? 2. Draw the Fisher projections and mirror images 3. Is there a plane of symmetry in the molecules 4. What is the R and S configuration of each chiral center? 5. Are the mirror images superimposable? 6. Are the mirror images entantiomers, meso, or diasteriomers? 7. What is the name of each compound? 53 Examples of Stereoisomers M r irro C3 H C3 H H S B r S M r irro C3 H C3 H H B r 2 C3 H B r B r B R r B r S * CB Hr Hr * CB C3 H B r H B R r H R H S H R H H Plane of Symmetry C3 H 1 C3 H C3 H 3 C3 H 4 Gn ric ee Frm la o u Enantiomers Non-superimposable mirror images Enantiomers = 1 & 2 Meso = 3 & 4 Diasteriomers = 1 & 3, 2 & 3, 1 & 4, 2 & 4 Names: 1. (2S,3S)-2,3-dibromobutane 3. (2S,3R)-2,3-dibromobutane Meso superimposable mirror images, i.e. they are the same compound 2. (2R,3R)-2,3-dibromobutane 4. (2S,3R)-2,3-dibromobutane 54 Sample Problem Solution Given in Lecture on the Black Board 1. Identify the chiral centers in the compound below with a asterisk. 2. Draw all the possible Fisher projections of the compound below and identify the mirror image pairs as entantiomers or meso. 3. Identify the R & S configuration of each chiral center. C2H O CO HH CO HH C2 H C3 H 55 9.10 Stereochemistry of Reactions: Addition of H2O to Alkenes Many reactions can produce new chirality centers from compounds without them What is the stereochemistry of the chiral product? What relative amounts of stereoisomers form? Example addition of H2O to 1-butene What is the mechanism for this reaction? 56 Achiral Intermediate Gives Racemic Product Addition via carbocation Top and bottom are equally accessible H2O nucleophile has 50:50 chance of adding to either side of empty p-orbital Important Rule: Nonstereoisomer reactants always make a racemic mixture of enantiomers!!! Proton added here 57 9.11 Stereochemistry of Reactions: Addition of H2O to a Chiral Alkene What is the sterochemical result of the addition of H2O to a chiral alkene R-4-methyl-1-hexene This is a different story. Now we are starting with a stereoisomer as a starting reagent. Product has 2 chiral centers R ? What kind of products are made here? 58 9.11 Stereochemistry of Reactions: Addition of H2O to a Chiral Alkene What is the sterochemical result of the addition of H2O to a chiral alkene R-4-methyl-1-hexene This is a different story. Now we are starting with a stereoisomer as a starting reagent. Product has 2 chiral centers R R&S Diastereomer products are made 59 SAMPLE PROBLEMS WORKED ON BOARD Predict the major organic products, including stereoisomers. Identify the R and S configuration. CH3 Br2 ? CH3 CH3 HBr ? 60 SAMPLE PROBLEMS WORKED ON BOARD Predict the major organic products from the bromination of cis-stilbene, including stereoisomers. Identify the R and S configuration. Are the products enantiomers only or are both enantiomers and meso formed? 61 9.12 Chirality at Nitrogen, Phosphorus, and Sulfur Other atoms can be chiral too, but it is much less common. N, P, S commonly found in organic compounds, and can have chirality centers Trivalent nitrogen is tetrahedral Does not form a chirality center since it rapidly flips Individual enantiomers cannot be isolated Gave example of football structure in lecture. 62 Also applies to phosphorus but it flips more slowly 63 9.13 Prochirality A molecule that is achiral but that can become chiral by a single alteration is a prochiral molecule 64 Prochiral Distinctions: Faces Planar faces that can become tetrahedral are different from the top or bottom A center at the planar face at a carbon atom is designated re if the three groups in priority sequence are clockwise, and si if they are counterclockwise Replacing with Br makes this Pro-R Replacing with Br makes this Pro-S 65 Prochiral distinctions, paired atoms or groups An sp3 carbon with two groups that are the same is a prochirality center The two identical groups are distinguished by considering either and seeing if it was increased in priority in comparison with the other If the center becomes R the group is pro-R and proS if the center becomes S Deuterium has a higher atomic weight than hydrogen. 66 Prochiral Distinctions in Nature Biological reactions often involve making distinctions between prochiral faces or or groups Chiral entities (such as enzymes) can always make such a distinction Example: addition of water to fumarate 67 9.14 Chirality in Nature and Chiral Environments Stereoisomers are readily distinguished by chiral receptors in nature Properties of drugs depend on stereochemistry Think of biological recognition as equivalent to 3-point interaction See Figure 9-17 68 ...
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