Ochem Chapter 4 - Chirality PDF

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Chirality 4.1 Intro to Chirality: Enantiomers Train of thought for determining molecule shape: Elemental composition → Empirical formula → Molecular formula → Constitution/Connectivity → Configuration What we’ve already touched: Cis-trans prefixes describe relative configurations called conformations. What we need to expand: - We need to include the concept of chirality, or “handedness” in molecules. - Formal definition: “A geometric figure has chirality if its mirror image can’t be superimposed on itself.” Where do we see chirality in Ochem? - Often when a carbon is attached to four different groups - Bromochlorofluoromethane (1) - Bromochlorofluoromethane (2) - In the above two links (which lead to simulations) you can see that the two molecules are almost like right hand and left hand, identical but not superimposable. This is best seen if you have two browser windows open at once. Big takeaway: Because the mirror images of such molecules differ in the arrangement of atoms in space, they are stereoisomers. In particular, they are enantiomers, stereoisomers related as mirror images. Enantiomer is a relative word, like “cousin” or “isotope.” You can’t have it as a single set apart object. “Them Ochem profs was showing me an enantiomer” ← Not only is that bad grammar, that is not organic-chemically correct. (w, x, y, z) ← When w, x, y, and z represent different atoms or groups, the exchange of two of them converts a structure into its enantiomer, while the exchange of 3 recreates the original structure. The surest test of chirality is mirror-image analysis, and a model is helpful

4.2 The Chirality Center When you’re looking for a chirality center, you’re looking for a tetrahedral (sp3 hybridized) carbon with four different atoms or groups attached). These groups can be a CH3 group, a H, a Br, a CH2, a CH, or some other element or combinations of elements. You can’t have chirality centers at carbons with couple or triple bonds (it has to sp3 hybridized) Different isotopes of the same element also count for finding chirality centers. Very important: Everything said already applies only to molecules with one chirality center each

4.3 Symmetry in Achiral Structures If you can find a plane of symmetry such that you have an identical half on each side of the mirror, it is achiral. If you can find a center of symmetry (such that a line drawn through the center of the molecule could extend straight from one element of the molecule to an identical element on the other side, it is achiral. Advice: -Planes of symmetry are easier to find, so start with plane symmetry, then center symmetry. Both will make a molecule achiral. A molecule without these is likely to be chiral, but use the superimposing test to be sure.

4.4 Optical Activity Optical activity is the ability for a chiral substance to rotate plane polarized light. (instrument used = polarimeter) The light used in such tests has a single wavelength, most often about 589 nm (D-line); a sodium lamp is common because its light has this wavelength. Process of analyzing the optical activity of chiral substances 1. A light source sends out an unpolarized, single-wavelength light 2. A filter polarizes the beam such that only the waves of a certain angle go through.

3. The beam then goes through a container of liquid or dissolved chiral substance in which one of the enantiomers is present in excess of the other. 4. The substance is optically active if the angle of the beam of light is shifted a little when going through the chiral substance. (All achiral substances are optically inactive.) The form of the molecule slightly shifts the plane of the beam of light. Enantiomers shift the beam of light in opposite directions but with the exact same magnitude. For example, one enantiomer might shift the plane of light -13.5 degrees while the other enantiomer would shift the plane exactly 13.5 degrees. Equal amounts of both enantiomers = no net rotation of the plane Figure 4.4 from the text

Important Terminology - Racemic mixture = equal presence of both enantiomers, optically inactive - Homochiral = all the molecules are of one enantiomer - Enantiopure = same as homochiral - Enantiomer excess (ee) = more of one enantiomer than the other, given in percentage (%) - Enantiomer ratio (ea) = ratio of percentage major (more present) enantiomer to the ratio of the minor enantiomer - ea = 80:20 enantiomeric = 80 % of one enantiomer, 20% of the other. Ee = 80% - 20% = 60%, so the ee of an 80:20 enantiomeric ratio is 60

Rotation → clockwise = (+), counterclockwise = (-) (+)-2-butanol, (-) -2-butanol, (±)-2-butanol. ± = racemic Length of tube containing the chiral substance affects the number of molecules the beam of light encounters. Twice the length of the tube equals twice the observed rotation. We need an equation that takes everything into account.

[α] = specific rotation, physical property of the substance c = concentration of sample in grams per 100 mL of solution l = length of the polarimeter tube α = observed rotation Relationship between enantiomeric excess and specific rotation.

Notation: 25

[α]𝐷 is the specific rotation of the substance when subjected light of the D-line (589 nm) at 25 degrees Celsius

4.5 Absolute and Relative Configuration 3D spatial arrangement of substituents at a chirality center is its absolute configuration. Relative configurations can be determined by interconversion experiments It’s really helps to have a model (virtual or physical) Here’s (+)-2-butanol: https://molview.org/?cid=444683 Here’s (-) -2-butanol: https://molview.org/?cid=84682

What I really appreciate about molview.org is that you can actually learn the name of the compound when you click on the links provided above. In Chrome at least, the name of the compound is displayed on the tab title

4.6 Cahn-Ingold-Prelog R,S notation In the Cahn-Ingold-Prelog (I’m gonna use the acronym CIP) system: - substituents are ranked in decreasing atomic order. Thus Br (atomic number of 35) will be ranked before F (9). - Next, we orient the molecule such that the lowest ranked atom is pointing away from us, perhaps attached by a dashes. - We next look at whether the line of decreasing priority goes counterclockwise or clockwise. - If it goes counterclockwise, the configuration is R - If it goes clockwise, the configuration is L. - There may be any combination of R, L, (-), and (+) - You tend to include both the R and the (-) --- or the L and the (+) -- together if both are known. - Again look at the screenshot

Notice the “r” and the “s” next to the (-) and (+), respectively.

Table 4.1 in the text is probably your best bet for a concise review of the CIP system 1. Higher atomic number takes precedence. 2. If two atoms attached to chirality center are identical, compare the atoms attached to them and use atomic number to determine priority 3. Work outward form chirality center, and compare all atoms attached to a particular atom before going down a chain

4. Evaluate substituents atoms one by one, not as groups 5. Multiply bonded atoms is considered to be replicated as a substituent of that atom. 6. Chirality centers inside rings are handled similarly. Try to find a lower and higher priority path around the ring\

Symmetry-breaking: Why does only one enantiomer often dominate, many times completely destroying the other? Homochirality sounds an awful lot like someone designed it or was planning it all out. It seems a little odd that the completely natural evolutionary system on its own would for billions of years only favor one enantiomer over another, if both are equally likely. Food for thought lol.

4.7 Fischer Projections Fischer projections are basically what we’re always drawing: This is S-Bromochlorofluoromethane

Vertical bonds = pointing away from us. Horizontal bonds = pointing toward us. We tend to have the lowest numbered element on top, in this case hydrogen. What we can do is take a 3-dimensional representation, orient it so that the lowest ranking element is pointing away from us, then determine the configuration from there.

This is R-2-butanol

4.8 Properties of Enantiomers Usual physical properties (density, melting point, boiling point) are same for enantiomers You guys gotta check this out!

Receptors in the nose are also chiral, or handed. Only certain enantiomers can fit in certain receptors

Chiral recognition: selective interaction with one of the enantiomers of a chiral compound. Check this out too.

Soo interesting!!

4.9 The Chirality Axis Chirality axis - an axis about which a set of atoms or groups is arranged so that the spatial arrangement is not superimposable on its mirror image. Think: left handed screw vs.right handed screw

Biaryls: compounds with two aromatic rings joined by a single bond

Rings are flat but overall molecules aren't, see this simulation for biphenyl: https://molview.org/?cid=7095 This “twisted” conformation helps reduce steric strain between nearby hydrogens. Swift rotation about the bond axis can occur; can be impeded when large substituents swing close to each other. Chiral biaryls are also called atopisomers. Atropisomers are related by rotation about a single bond but are capable of independent existence due to hindered rotation as a result of large substituents repelling each other.

4.10 Chiral Molecules with Two Chirality Centers. When we have two Chirality centers, we do analysis on both centers

Diasteroemers are stereoisomers that aren’t mirror images. To get an enantiomer, change both chirality centers To get a diastereomer, change only one center. Diastoreomers can have different rotations To write a Fischer projection, started it with an eclipsed conformation.then convert to Fischer.

Erythro = same side Threo = different sides Diastereomers can have radically different physical properties. Remember: Cis and trans isomers are diastereomers of each other.

4.11 Achiral Molecules with Two Chirality Centers Achiral molecules with chirality centers = meso forms

Often in cyclic compounds, the cis and trans can be meso forms. Conformational enantiomers - enantiomers interconvertible by a conformational change.

4.12 Molecules with Multiple Chirality Centers Maximum number of stereoisomers for a particular constitution is 2n, where n is the number of chirality centers Equivalent substitution can lead to meso forms, which leads to a number less than 2n. Steroids → multiple chirality centers Remember: Diastereomers are stereoisomers that are not enantiomers, any object can only have one mirror image. For cholic acid: - 11 chirality centers - 211 stereoisomers → 2048 total stereoisomers - One is cholic acid, one is its enantiomer, and the other 2046 are diastereomers

Many proteins have hundreds of chirality centers.

4.13 Resolution of Enantiomers Resolution: the process of treating a racemic structure to isolate its enantiomers Process often entails converting enantiomers into diastereomers, isolating the different diastereomers, and converting them back into enantiomers

Converting to diastereomers is often a simple acid-base reaction Often specific enzymes are used to take advantage of the different reaction rates of enantiomers.

4.14 Chirality Centers other than Carbon Silicon, since it also can have a tetrahedral bonding system, can also be a chirality center. Trigonal pyramidal molecules are chiral if the central atoms bear different groups. Thus nitrogen could also be a chiral center

Phosphorus (same column in PTable as nitrogen) can also work; easier to analyzed because it has a slower inversion rate. When applying CIP to a chiral center with an unshared e- pair, the e- pair has the lowest rank.

4.15 Review section...