Stereochemistry. Dr Morteza Mehrdad University of Guilan, Department of Chemistry, Rasht, Iran

Transcription

1 9 Stereochemistry استریوشیمی Dr Morteza Mehrdad University of Guilan, Department of Chemistry, Rasht, Iran Based on McMurry s Organic Chemistry, 7 th edition

2 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 left-hand glove. The property is commonly called»دستواره«handedness از نظر معنی لغت:}عادت به استفاده از یک دست پیش از دست دیگر{ Organic molecules (including many drugs) have handedness that results from substitution patterns on sp 3 hybridized carbon 2

3 Why this Chapter? Handedness is important in organic and biochemistry Other types of stereoisomers besides cis/trans Molecular handedness makes possible specific interactions between enzymes and substrates effecting metabolism and pharmaceuticals 3

4 انانتیومر Examples of Enantiomers Molecules that have one carbon with 4 different substituents have a non-superimposable mirror تصویر آیینه ای انطباق ناپذیر image Enantiomers = non-superimposable mirror image stereoisomers Enantiomers have identical physical properties (except for one) Build molecular models to see this 4

5 کایرالیته Chirality If an object has a plane of symmetry it s the same as its mirror image A plane of symmetry divides an entire molecule into two pieces that are exact mirror images Achiral ناکایرال means that the object has a plane of symmetry Molecules that are not superimposable with their mirror images are chiral (have handedness) Hands, gloves are prime examples of chiral object They have a left and a right version Organic molecules can be Chiral or Achiral 5

6 مرکزهای کایرالیته Chiral Centers A point in a molecule where four different groups (or atoms) مرکز are attached to carbon is called a chiral center کایرالیته Such carbons are referred to as chirality centers, although other terms such as stereocenter فضایی,مرکز asymmetric مرکز فضازا and stereogenic center,مرکز بی تقارن center have also been used. A chiral molecule usually has at least one chiral center 6

7 Chiral 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 صفحه تقارن ندارد و کایرال است 7

8 فعال نوری 9.3 Optical Activity قطبیده مسطح Light restricted to pass through a plane is plane-polarized A polarimeter measures the rotation of plane-polarized light that has passed through a solution Rotation, in degrees, is [ ] Clockwise (+) = dextrorotatory; Anti-clockwise (-) = levorotatory چپ گردان راست گردان Plane-polarized light that passes through solutions of achiral compounds remains in that plane ([ ] = 0, optically inactive) Solutions of chiral compounds rotate plane-polarized light and the molecules are said to be optically active 8

9 چرخش نوری Measurement of Optical Rotation The more molecules of a chiral sample are present the greater the rotation of the light = concentration dependent To have a basis for comparison, define specific rotation, [ ] D forچرخش an optically active compound مخصوص Specific rotation is that observed for 1 g/ml in solution in a cell with a 10 cm path using light from sodium metal vapor (589 nm) (observed rotation in degrees) [ ] D (pathlength in dm)(concentration in g/ml) l C The specific rotation of the enantiomer is equal in magnitude but opposite in sign (+)-lactic acid = +3.82; (-)-lactic acid =

10 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 solutions contain mirror image isomers, called enantiomers and they crystallized in distinctly different shapes such an event is rare A (50:50) racemic mixture مخلوط راسمیک of both crystal types dissolved together was not optically active The optical rotations of equal concentrations of these forms have opposite optical rotations 10

11 تالیدومید THALIDOMIDE One asymmetric carbon atom, exists as 2 enantiomers S-Enantiomer sedative R-Enantiomer Teratogen مسکن عامل ناقص کنندگی جنین تالیدومید به عنوان یک داروی آرامبخش در اواخر دهه 50 میالدی توسط یک شرکت داروسازی آلمانی به نام گروننتال تولید شد و به بازار آمد. از این دارو برای درمان تهوع صبحگاهی زنان باردار و مشکالت بیخوابی استفاده میشد.

12 Sequence Rules for Specification of Configuration قواعد ترتیب برای مشخص کردن پیکربندی A general method applies to determining the configuration at each chiral 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 chiral center The groups are ranked in an established priority sequence and compared use the same priority ranking as we did for E/Z names The relationship of the groups in priority order in space determines the label applied to the configuration, according to a rule 12

13 Ranking Priorities: Cahn-Ingold-Prelog Rules [REVIEW CH. 6] RULE 1 Must rank atoms that are connected at comparison point Higher atomic number gets higher priority Br > Cl > S > P > O > N > C > H 13

14 Extended Comparison RULE 2 If atomic numbers are the same, compare at next connection point at same distance Compare until something has higher atomic number Do not combine always compare 14

15 Dealing With Multiple Bonds: RULE 3 Substituent is drawn with connections shown and no double or triple bonds 15

16

17 Method Assign each group priority 1-4 according to Cahn-Ingold-Prelog Rotate the assigned molecule until the lowest priority group (4) is in the back, look at remaining 3 groups in a plane Clockwise movement is designated R (from Latin for right ) Counterclockwise is designated S (from Latin word for left ) چپ sinister راست rectus 17

18 18

19 هیدروکسی بوتانوییک اسید دیاسترومرها 9.6 Diastereomers Molecules with more than one chiral center have mirror image stereoisomers that are enantiomers In addition they can have stereoisomeric forms that are not mirror images, called diastereomers

20 Diastereomers Diastereomers are similar, but they aren t mirror images Enantiomers have opposite configurations at all chiral centers; Diastereomers are opposite at some, but not all chiral centers Diastereomers have different physical properties Epimers اپیمر are diastereomers different at only 1 chiral center 20

21 ترکیبات مزو 9.7 Meso Compounds Tartaric acid has two chiral centers and two diastereomeric forms One form is chiral and one is achiral, but both have two chiral centers An achiral compound with chiral 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 Identical substitution on both chiral centers 21

22 9.8 Racemic Mixtures and The تفکیک انانتیومرها 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 22

23 Using an Achiral amine doesn t change the relationship of the products Still can t separate the Enantiomeric Salts 23

24 Using a Chiral amine changes the relationship of the products Now we can separate the Diastereomeric Salts 24

25 9.9 A Review of Isomerism The flowchart summarizes the types of isomers we have seen

26 26

27 Constitutional Isomers ایزومرهای ساختمانی Different order of connections gives different carbon backbone and/or different functional groups 27

28 استریوایزومرها Stereoisomers Same connections, different spatial arrangement of atoms Enantiomers (nonsuperimposable mirror images) Diastereomers (all other stereoisomers) Includes cis, trans and configurational diastereomers 28

29 9.10 Stereochemistry of Reactions: Addition of H 2 O to Alkenes Many reactions can produce new chiral centers from compounds without them What is the stereochemistry of the chiral product? What relative amounts of stereoisomers form? Example addition of H 2 O to 1-butene 29

30 Achiral Intermediate Gives Racemic Product Addition via carbocation Top and bottom are equally accessible Achiral reactant + Achiral reactant = Optically Inactive Product Optical Activity doesn t come from nowhere فعالیت نوری از ناکجاآباد نمی آید 30

31 Addition of H 2 O to a Chiral Alkene What is the sterochemical result of the addition of H 2 O to a chiral alkene R-4-methyl-1-hexene Product has 2 chiral centers -Chiral + Achiral = Optically Active -Chiral Intermediate has different top and bottom sides -Amounts of the two products will be different -Product will have optical activity 31

32 9.12 Chirality at Nitrogen, Phosphorus, and Sulfur N, P, S commonly found in organic compounds, and can have chiral centers Trivalent nitrogen is tetrahedral Does not form a chiral center since it rapidly flips Individual enantiomers cannot be isolated = Achiral 32

33 Also applies to phosphorus but it flips more slowly Can isolate individual enantiomers = Chiral Trivalent Sulfur Cations are also Chiral 33

34 پروکایرالیته 9.13 Prochirality A molecule that is achiral but that can become chiral by a single alteration is a prochiral molecule اگر مولکولی ناکایرال باشد و فقط با یک دگرگونی کایرال گردد مولکول پروکایرال نامیده می شود Re and Si are used to describe the faces of the prochiral sp 2 reactant 34

35 Prochiral distinctions, paired atoms or groups An sp 3 carbon with two groups the same is also a prochiral 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 pro-s if the center becomes S 35

36 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 36

37 Chirality in Nature and Chiral Environments Enantiomers have same physical properties, different biological ones 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 Enzymes can make only one enantiomer from an achiral reactant In the chiral environment, pro-r and pro-s are chemically different هنگامی که یک مولکول پروکایرال در محیط کایرال قرارمی گیرد دو استخالف قرمز رنگ قابل تمیز خواهند بود فنجان قهوه= ناکایرال - در محیط کایرال دست فقط از یک طرف می توان قهوه را نوشید 37

38 Biological Molecules RULE - Enzymes are chiral reagents because their binding site is chiral

39 39