Organic Chemistry Jonh Mc Murry17

Organic Chemistry Jonh Mc Murry17 - 300 CHAPTERS...

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Unformatted text preview: 300 CHAPTERS Stereochemistrv Figure 9.9 Assigning configu- ration ‘to la} (—leglyceraldehyde and (b) l i l—alanine. Both happen to have the Sconfiguration, although one is levorotatory and the other is dextrorotalory. WORKED EXAMPLE 9.3 Strategy Solution (a) H . r-fi-m. | ' m \ .C , “0'7 \3'3 t ' ..: Cl-I2ClH = ‘u (Sl-Glyceraldehyde [(SH-l-2,3—Dihvdroxypr0panal] [019 = -847 lb) H we Cl 2 H 1 — HEN") \t‘21':;. FBCKéuc-L ‘ 33'" CW: \‘ i l tin ‘/ . w ’ '9 {SI-Alanine [(S)-l+)—2-Aminopr0panoic acid] [IXJD = +8.5 Assigning R or S Configuration to Chirality Centers in Molecules Orient each of the following drawings so that the lowest-priority group is toward the rear, and then assign R or 3 configuration: la) (bl ? \G) GQC‘\® a l D \./ \ it takes practice to be able to visualize and orient a molecule in three dimensions. You might start by indicating where the observer must be located—180° opposite the lowest—priority group. Then imagine yourself in the position of the observer, and redraw what you would see. In (a), you would be located in front of the page. toward the top right of the mole— cule. and you would see group 2 to your left, group 3 to your right, and group 1 below you. This corresponds to an R configuration. t; " ll \5/ ‘er Q/ [/1 (al ‘ \. ’ Observer ll F? configuration _ Exam-LE? Solution Probiem 9.7 Problem 9.8 95 Sequence Rules for Specifying Configuration 301 in (b), you would be located behind the page toward the top left of the molecule from your point of View, and >01] would see group 3 to your left, group 1 to your right, and group 2 below you. This also corresponds to an R configuration. /\ “(Z /—‘ “itxx ®l _\\f x 9 k2) \j/j ’I 4 /) \.‘ an 2 ll l/i’ / Observer of y. l, , / (bl R configuration Drawing the Three-Dimensional Structure of a Specific Enantiomer Draw a tetrahedral representation of (R)-2-chlorobutane. Begin by assigning priorities to the four substituents bonded to the chirality center: (1) *CI, (2) eCHZCl-lg, (3) ~CH3, ti) — it To draw a tetrahedral representation of the molecule, orient the lowest—priority —H group away from you and imagine that the other three groups are coming out of the page toward you. Then place the remaining three substituents such that the direction oftravel l a 2 —> 3 is cloekwise (right turn), and tilt the molecule toward you to bring the rear hydrogen into View Using molecular models is a great help in working problems of this sort. i H _ 7' Cl CH CH a \C/ 2 3 ’IC\ (Hi-z-Chlorobutane 1 H C‘/ CH CH 3 2 3 ‘ Assign priorities to the following sets of substituents: (a) —H, —OH, *CHQCH3, —CH2C1‘120H (b) eCOZH, ~COZCH3, WCIIZOH, on (c) —CN, —CH2NHZ, —Cl-l3\lllCH3, —Nl-[2 ((1) *SH, ~c1—125cn3, ecug, e55C1—i3 Orient each of the following drawings 50 that the lowest-priority group is toward the rear. and then assign R or 5 configuration: [8) (I 1 lb) (cl ® 302 CHAPTERS Siereochemistry Problem 9.9 Problem 9.19 UIII Problem 9.11 9.6 Thomson Click Organic Interactive to use a web- based palette to draw stereoisomers. Assign R or 5 configuration to the chirality center in each of the following molecules: (a) eHs [bi ('3H [cl H\C¢O —'C\ /C\ l H'/ COZH H3C \‘COZH Hr—C—dOH HS H 5 CHZOH 'l-lrani :1 Pol-r21 Utuli u u. Dr‘lrul ronrocnntati LILAILLLIL l \1 l l you“. An n? (CL? nfqnnl (’7: 1 UL VI kg _nD Uflrnvu ant-anal IILULAUA \JI-u-Fciuuii u L]. r\ u LUAjk'LLLLUJI Assign R or 5 configuration to the chirality center in the following molecular model of the amino acid methionine (blue 2 N, yellow 2 S): e e ‘r _, - f u _ a? W Diastereomers Molecules like lactic acid, alanine, and glyceraldehyde are relatively simple because each has only one chirality center and only two stereoisomers. The sit- uation becomes more complex, however, with molecules that have more than one chirality center. As a general rule, a molecule with n chirality centers can have up to 2“ stereoisomers (although it may have fewer, as we’ll see shortly). Take the amino acid threonine (Z-a mino-S—hydroxybutanoic acid), for example. Since threonine has two chirality centers (C2 and C3), there are four possible stereoisomers, as shown in Figure 9.10. Check for yourself that the R,S configu- rations are correct. The four stereoiSOmers of 2-amino-3-hydroxybutanoic acid can be grouped into two pairs of enantiomers. The 2R,3R stereoisomer is the mirror image of 25,35, and the 2R,35 stereoisorner is the mirror image of 25,3R. But what is the relationship between any two molecules that are not mirror images? What, for example, is the relationship between the 21%,3R isomer and the ZR,3S isomer? They are stereoisomers, yet they aren’t enantiomers. To describe such a rela- tionship, we need a new term—diasrereomei: Diastereomers are stereoisomers that are not mirror images. Since we used the right-hand/left-hand analogy to describe the relationship between two enantiomers, we might extend the analogy by saying that the relationship between diastereomers is like that of hands from different people. Your hand and your friend's hand look similar, but they aren‘t identical and they aren’t mir— ror images. The same is true of diastereomers: they're similar, but they aren’t identical and they aren’t mirror images. 9.6 Diastereomers 303 rag-Mk“, . c C nymkém H2N\<:3,H I, r 7 I \ /C\ x": xcx li) Ht) 3 H HO 3 H H 1 H ; OH CH:- Cll-l-3 CH; 23,35 25,3]? Enantiomers Enantiomers Figure 9.10 The four stereoisomers of 2—amino-3-hydrovautanoic acid. Note carefully the difference between enantiomers and diastereomers. Bnantiomers have opposite configurations at all chirality centers, whereas diastereomers have opposite configurations at some (one or more) chirality cen- ters but the same configuration at others. A full description of the four stereo- lSOlIlerS of threonine is given in Table 9.2. Of the four, only the 25,3R isomer, MD: —28.3, occurs naturally in plants and animals and is an essential human nutrient This result is typical: most biological molecules are chiral, and usually only one stereoisomer is found in nature. _ Table 9.2 Relationships among the four Stereoisoniersof Threunine Stereaisomer Enantiumer Diastereomer ZR,3I<' 2N3? 2H,!“ and 2.5.3:” 23,35 2R,3R 2&3}; and 25',I5R 2H,3 \ 2.34M 2R,3h‘ and 25,35 2*},3li' 2133‘; 211,31? and 25.3? In the special case where two diastereomers differ at only one chirality cen- ter but are the same at all others, we say that the compounds are epimers. Cholestanol and coprostanol, for instance, are both found in human feces and 304 Problem 9.12 Problem 9.13 Problem 9.14 CHAPTER 9 Stereochemistry both have nine chirality centers. Eight of the nine are identical, but the one at C5 is different. Thus, cholestanol and coprostanol are epimeric at C5. Cholestanol Coprostanol Epirnei‘s One of the following molecules (a)—(d) is D-erythtose 4-ph05phatc, an intermediate in the Calvin photosynthetic cycle by which plants incorporate CO; into carbo- hydrates. it D—ery’rhrose 4-phosphate has R stereochemistry at both chirality centers, which of the structures is it? Which of the remaining three structures is the enan- tiomer of o-erythrOSE 4—phosphate. and which are diastereomers? (a) H\C40 (b) I-i\C//O (c) H\C¢O (d) H\C¢O HKCAOH HOKCAH H~¢AOH HO-éAH | l i l Hr9~0H HVC‘OH HorcwH How¢~H CH20P032‘ CH20P032" 04201903? Cuzoeof' Chloramphenicol, a powerful antibiotic isolated in 1949 from the Streptomyces venezueiae bacterium, is active against :1 broad spectrum of bacterial infections and is particularly valuable against typhoid fever. Assign R,S configurations to the chirality centers in chiorarnphenicol. /\ Chloramphenicol H NHCOCHCI2 OZN Assign R,S configuration to each chiraiity center in the following molecular model of the amino acid isoleucine (blue : N): 9.7 Figure 9.11 A symmetry plane through the C2—C3 bond of mesoetartaric acid makes the molecule achiral. 9.7 MesoCompounds 30! Mesa Compounds Let’s look at one. more example of a compound with more than one chirality center, the tartaric acid used by Pasteur. The four stereoisomers can be drawn as follows: lVlirrrir Mirror lei-EH my a? HEQXH I]|;:[\ZJ.l HEC‘EIOH H0233)” lilfiélOI-l HO:;/|-I | Ha£$‘n a/g‘oH H;§\OH HO;$\H u , H i 41l;:[,3:{l'l .m t | -'lC.J-;l-l 2R,3R I 25,35 2R,3S 23,3F? The mirror—image 2R,3R and 28,38 structures are not identical and therefore represent a pair of enantiomers. A close look, however, shows that the 2R,3$ and 25,312 structures are identical, as can be seen by rotating one structure 180°. l‘_f;l.ii-l “T792” H\_l/OH \, HO\l/H J 3C Hotel: 2C \ f K ‘.\H/ l \DH HO/ 3 \H 2 (10;:- 5—3 " 4 mil 7 23,38 25,3Fl Identical The 2R,35 and 25,312 structures are identical because the molecule has a plane of symmetry and is therefore achiral. The symmetry plane cuts through the C2—C3 bond, making one half of the molecule a mirror image of the other half (figure 9.11). Because of the plane of symmetry. the molecule is achiral, despite the fact that it has two chirality centers. Compounds that are achiral, yet contain Chirality centers, are called meso (meezo) compounds. Thus, tartaric acid exists in three stereoisomeric forms: two enantiomers and one meso form. 306 CHAPTERS Stereochemistry Some physical properties of the three stereoisoniers are listed in Table 9.3. The (+)- and (—l—tartaric acids have identical melting points, solubilities, and densities but differ in the sign of their rotation of plane-polarized light. The meso isomer, by contrast, is diastereomeric with the (+) and (u) forms. As such. it has no mirror-image relationship to (-l—)- and (—)-tartaric acids, is a different c0mpound altogether, and has different physical properties. __ Table 9.3 Some Properties ofthe Stereoisomers of Tartaric Acid Melting Density Solubility at 21] 3C Stereoisomer point (“8} [n]n (g/cm3l (g/‘lDB mL H20) [-l-l 168—170 +12 J..759S 139.0 (“.5 1687170 ’12 1.7595 139.0 R1650 l 46e 11-18 0 1.6660 125.0 Distinguishing Chirai Compounds from Mesa Compounds WORK-Esp EXAMPLE.9;5: Does cisi,2-dirriethylcyclobutane have any chirality centers? Is it chiral? Strategy To see whether a chirality center is present, look for a carbon atom bonded to four different groups. To see whether the molecule is chiral, look for the presence or absence of a symmetry plane. Not all molecules with chirality centers are chiral Overallameso compounds are an exception. Solution A look at the structure of cis«1,2—dimethylcyclobutane shows that both methyl- bearing ring carbons (C1 and C2) are chirality centers. Overall, though, the com- pound is achiral because there is a symmetry plane bisecting the ring between C1 and C2. Thus, the molecule is a rneso compound. S‘;‘lllill<!l!‘,’ plant: H3C CH3 i. i e H H Problem 9.15 Probiem 9.16 Which of the following have a meso form? (Recall that the -ol suffix refers to an alco— hol, ROH.) (a) 2,3-Butanediol (b) 2,3-Pentanediol (c) 2,4—Pentanediol Problem 9.17 9.8 9.8 Racemic Mixtures and the Resolution of Enantiomers 307 Does the following structure represent a meso compound? It so, indicate the sym- metry plane. “figur #5 A-Qfiiamgfignébe_ Racemic Mixtures and the Resolution of Enantiomers Let’s return for a last look at Pasteur’s pioneering work. Pasteur took an optically inactive tartaric acid salt and found that he could crystallize from it two opti- cally active forms having what we would now call the 2R,3R and 25,35 contigu- rations. But what was the Optically inactive form he started with? It couldn't have been mesa-tartaric acid, because mesa-tartaric acid is a different chemical compound and can't interconvert with the two chiral enantiomers without breaking and re-forming chemical bonds. The answer is that Pasteur started with a 50:50 mixture of the two chiral tar- taric acid enantiomers. Such a mixture is called a racemic (ray—see-mic) mixture, or racemate, and is denoted either by the symbol (i) or the prefix (1,! to indicate an equal mixture of dextrorotatory and levorotatory forms. Racemic mixtures show no optical rotation because the (+) rotation from one enantiomer exactly cancels the (—) rotation from the other. Through luck, Pasteur was able to sepa» rate, or resolve, racemic tartaric acid into its (+) and (—) enantiomers. Unfortu- nately, the fractional crystallization technique he used doesn’t work for most racemic mixtures, so other methods are needed. The most common method of resolution uses an acid—base reaction between a racemic mixture of chiral carboxylic acids (RCOQH) and an amine baSe (RNHZ) to yield an ammonium salt. O 0 g + Hue—m > H R/ \OH R/ \O‘TNaw Carboxylic Amine Ammonium salt acid base To understand how this method of resolution works, let’s see what happens when a racemic mixture of chiral acids, such as (+)- and (—)-lactic acids, reacts with an achiral amine base, such as methylamine, CH3NHZ. Stereochemically, the situation is analogous to what happens when left and right hands (chiral) pick up a ball (achiral). Both left and right hands pick up the ball equally well, and the products—ball in right hand versus ball in left hand—are mirror images. In the same way, both i t)- and (~)~lactic acid react with methylamine equally 308 CHAPTER 9 Stereochemistrv well, and the product is a racemic mixture of methylammonium (-lJ-lactate and methylammonium (ell—lactate (figure 9.12). Figure 9.12 Reaction of Cl} H 1 _ martin racemic lactic acid with achiral !' 2 ‘i if "“ '5 methylamine leads to a racemic (H) ,C _ 1, mixture ofammonium salts H’l \Cl'b i H! \C"':': HQ l-lU \\ Healt " "'ll‘ll-l \‘ + l Emu-rm Eriantinmers { ' _ __ / .r‘llt H(_1\ lIC!\ {a Hx L l H\ Uri) (3) ‘c/ i ‘c/ l _. iii/{yd I :.-|c-i;j— Milk-ii,“ i3 .- Ssalt Racemic lactic acid Racemic ammonium salt (50% Fl, 50% S) (50% F1. 50% 5) Now let's see what happens when the racemic mixture of (+)- and {—l-lactic acids reacts with a single enantiomer of a chiral amine base, such as (R)-1-phenyl- elhylamine. S'lereochemically, the situation is analogous to what happens when left and right hands (chiral) put on a right-handed glove (also chiral). Left and right hands don't put on the same glove in the same way. The products—right hand in right glove versus left hand in right glove—are not mirror images; they’re altogether different. In the same way, (+)- and (—J-lactic acids react with (R)-1-phenylethylamine to give two different products (Figure 9.13). (IO-Lactic acid reacts with Ci); fir); I-I :l‘~i l l ' R 1C ' . ,C i: ' \ i i \CUI‘T- |\'I|_. Hx/ \CHR Hit. -\|_, \Q. HO ‘ r HO l-w-if il I ’ if. I, \\ II "x," '\ .X r g' —’——" 1' -."'-\*'l.::|= Ill-E‘ A” 9-353” + --—— r "acme: 5 + H0 l it] 'i E '"I-1 r |-|.‘\ ill-lg Hr\\ Ci'iri IS) ‘c/ ' i c’ ' . ‘ . fix :‘ijijj : « (filly i'U-i Flacemic lactic acid ‘“ I ‘fi' ‘——‘—’ [50% H, 50% S) An S,Fl’ salt Figure 9.13 Reaction of racemic lactic acid with (Hl-l-phenvlethylamine yields a mixture of diastereomeric ammonium salts. wen-Kan EXAMPLE tits Solution Problem 9.18 Problem 9.19 9.9" 98 AReview of lsomerism 305 (R)-l-phenylethylamine to give the RR salt, and (SJ-lactic acid reacts with the R amine to give the 5,]? salt. The two salts are diastereomers; they are different compounds, with different chemical and physical properties. It may therefore be possible to separate them by crystallization or some other means. Once sep— arated, acidification of the two diastereomeric salts with a strong acid then allows us to isolate the two pure enantioniers of lactic acid and to recover the chiral amine for reuse. Predicting the Chirality ofa Product We'll see in Section 21.3 that carboxylic acids (RCOZH) react with alcohols (R’Oi—l) to form esters [RCOZR’t Suppose that (:)-lactic acid reacts with CHgOl‘l to form the ester, methyl lactate. What stereochemistry would you expect the productts) to have? What is the relationship of the products? HO 0 Acid HO O I ll ti ti l ll emoticon + IZTE‘lTl-l m CH3CHcmz~i3 + mo Lactic acid Methanol Methyl lactate Reaction of a racemic acid with an achlral alcohol such as methanol yields a racemic mixture of mirroreiinage (enantiomeric) products. COQH lCOgl’l $02lfirl3 $02Cl'l3 l ':"'l .l_"!"a .C + C. —‘.‘ ,C + C.‘ HO“/ \CH3 H3C/ \‘OH Amd HO‘] \CH3 H3C/’\‘OH H H catalyst H H (SI-Lactic acid (Hi-Lactic acid Methyl Methyl (Si-lactate (Bl-lactate Suppose that acetic acid (Ctl‘rCOZH) reacts with (S)-2—butanol to form an ester [SEC Worked Example 9.6!. What stereochemistry would you expect the product(s) to have? What is the relationship of the products? 0 CH3 Ill CH3CDCHCH2CH3 + Acid 0 OH ll catalyst I CH3COH + CH3CHCH2CH3 H20 Acetic acid 2»Butano| sec-Butyl acetate What stereoisomers would result from reaction of (:)-lactic acid with (SH-phenyl- ethylamine, and what is the relationship between them? A Review of Isomerism As noted on several previous occasions, isomers are compounds that have the same chemical formula but different structures. We’ve seen several kinds of iso- mers in the past few chapters, and it’s a good idea at this point to see h0w they relate to one another (figure 9.14). 310 CHAPTERS Stereochemistry Figure 9.14 A summary ofthe different kinds of isomers. Isomers Constitutional isomers ,_| l l Stereoisomers Enamiomers Diastereomers imirror‘eimagel (non—mirror—image) Configurational Cis-trans diastereomers diastereomers There are two fundamental types of isomers, both of which we’ve now encountered: constitutional isomers and stereoisomers. ( (institutional isomers (Section 32) are compounds whose atoms are con- nected differently, Among the kinds of constitutional isomers we’ve seen are skeletal, functional, and positional isomers. Different carbon CH3 skeletons | CH3CHCH3 and CH3CH2CH2CH3 2—Methylpropane Butane Different functional CH3CHzCi‘rl and CH3CJCH3 groups Ethyl alcohol Dimethyl ether Different position of "till i functional groups l and Isopropylamine Propylamine Stei'mison'iers (Section 4.2) are compounds whose atoms are connected in the same order but with a different geometry. Among the kinds of stereoisomers we’ve seen are enantiomers, diastereomers, and cis—trans isomers (both in alkenes and in cycloalkanes). Actually, cis—trans isomers are just another kind of diastereomers because they are non—mirror—image stereoisomers. Ellfil‘flitifilei"; i,-Ifjr..-: .-‘ {'1 ‘ (nonsuperimposable mirror-image :-a r:"}C\0H HO/ vigil: stereoisomersl H H ‘I [Bl-Lactic acid [S)-Lactic acid .,.-:-‘i.3;3'1‘-:'-c_\ .3.) 5-. XII-32: (nonsuperimposable, H\ i ,NH2 nonemirror‘image (I: stereoisomersl C HO’ 3 \H 2R.3R—2-Amino-3- 2R,35—2-Amino~3— hydroxybutanoic acid hydroxybutanoic acid ...
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Organic Chemistry Jonh Mc Murry17 - 300 CHAPTERS...

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