Acetals & Hemiacetals and Chiral Molecules

Goals for the Day: Distinguish between a hemiacetal, acetal, hemiketal, and ketal Learn to recognize these groups in sugar molecules Chirality: recognizing when a compound is chiral. Fisher Projections (and how to tell if the molecule is chiral by looking at the Fisher Projection). START Carbohydrates! 

Acetals from Aldehydes Alcohol adds to the aldehyde carbonyl producing a hemiacetal. When a second alcohol adds, it forms an acetal.

Ketals from Ketones Ketones are less reactive than aldehydes because the carbonyl carbon is more positive in aldehydes. react with one alcohol molecule to form a hemiketal, and react with a second alcohol molecule to form a ketal hemiketal ketal

Products of the reaction of an alcohol with an aldehyde or ketone)… Hemi acetal: from an aldehyde, “halfway” to an acetal (so it has an H, OH, and 1 OR). Acetal: from an aldehyde, “full” (so it has a H and 2 OR groups). Hemiketal: from a ketone, “halfway” to a ketal (so it has 2 R groups, an OH and 1 OR). Ketal: from a ketone, “full” (so it has 2 R groups and 2 OR groups).

Products of the reaction of an alcohol with an aldehyde… Hemi acetal: “halfway” to an acetal (so it has an H, OH, and 1 OR). Acetal: “fully reacted” (so it has a H and 2 OR groups). Continues to react…

Products of the reaction of an alcohol with a ketone)… Hemiketal: “halfway” to a ketal (so it has 2 R groups, an OH and 1 OR). Ketal: “fully reacted” (so it has 2 R groups and 2 OR groups). Continues to react…

How to tell the difference?

Learning Check Identify each as a hemiacetal, acetal, hemiketal or ketal.

Solution hemiacetal ketal

Cyclic Hemiacetals In glucose, a cyclic hemiacetal between the C═O group and the –OH group on carbon 5, forms a stable, six-atom ring.

Let’s work through a few to help you recognize what the groups are… (is this a hemiacetal, acetal, hemiketal, or ketal)? 

We know that it’s not a “hemi” Because there isn’t an OH group (so a & c can be crossed off. Since the other two groups are both Carbons, it is a ketal…

is this a hemiacetal, acetal, hemiketal, or ketal)?  a) hemiketal b) ketal c) hemiacetal d) acetal

a) hemiketal b) ketal c) hemiacetal d) acetal We know that this one is a “hemi” because of the OH. It is a hemiketal since there are 2 R groups (no Hydrogens) attached to the pink carbon

One more poll… is this a hemiacetal, acetal, hemiketal or ketal?

Answer…it’s a hemiacetal… We know it’s not from a ketone because there is a hydrogen on the structure, so we can cross off “c” and “d.” We know it’s hemi because of the OH group… 

Learning Check Draw the condensed structural formula of the acetal formed by adding CH3OH to butanal. (Hint on next slide)…

Learning Check: Hint Butanal is shown. In adding CH3OH, you add the OCH3 to the carbonyl carbon & the H to the oxygen…

Hemiketal Product… Butanal is shown. In adding CH3OH, you add the OCH3 to the carbonyl carbon & the H to the oxygen…

It can continue to add to give an acetal…(2 OR groups)

Solution (showing the carbons…) Same thing, just showing the c’s and H’s (and O’s). 

Cyclic Acetals (Important to be able to recognize these in sugars) form when an alcohol adds to a cyclic hemiacetal. are very important in carbohydrate chemistry. It is the type of linkage that bonds glucose molecules to other glucose molecules in the formation of disaccharides and polysaccharides.

Glucose + Glucose = Maltose is a disaccharide consisting of two glucose molecules linked by an acetal bond (shown in red). has one glucose that retains the cyclic hemiacetal bond (shown in green).

Maltose Maltose, a disaccharide, is produced from the hydrolysis of the starches in grains, such as barley.

Last one to try… Which carbon is the one where the ring formed? Is this a hemiacetal or an acetal?

Answer… It has an OR, R, H, and OH, so it is “halfway” to being an acetal… It is a hemiacetal! 

Chirality (handedness) in organic molecules A molecule is said to be chiral if it can exist as isomers (called enantiomers) that are nonsuperimposable mirror images of each other. We say these molecules exhibit “handedness,” like our nonsuperimposable mirror image left and right hands. Enantiomers rotate plane-polarized light by the same angle but in opposite directions.

Chirality (handedness) in organic molecules Many of the molecules produced and used by organisms exhibit a specific handedness. This is important because the response of an organism to a particular molecule often depends on how that molecule fits a particular site on a receptor molecule in the organism. one enantiomer of penicillamine is a potent anti-arthritic agent whereas the other enantiomer is highly toxic In designing pharmaceuticals, chemists must be concerned about which enantiomer is the active one—the one that fits the intended receptor.

A chiral molecule responsible for the smell of lemons and oranges Limonene A chiral molecule responsible for the smell of lemons and oranges

These are examples of stereoisomers that are called “enantiomers”. First, notice that each carbon in both examples are connected to 4 DIFFERENT GROUPS/THINGS/SHAPES! Now notice that only one arrangement in space around the C will fit into the receptor site. Figure: 19-02 Title: chiral reactants and chiral reaction sites Caption: A chiral reactant and a chiral reaction site. The enantiomer at the top fits the reaction site like a hand in a glove, but the enantiomer at the bottom doesn't fit and therefore can't be a substrate for this enzyme. Notes: These are examples of stereoisomers that are called “enantiomers”. “enantiomers” are mirror-images that cannot be superimposed.

This is the only chiral carbon in this molecule. To be chiral, a carbon atom must have 4 different group attached to it.

Chirality (handedness) in organic molecules Molecules in nature ofteh have mirror images, and often one stereoisomer has a different biological effect than the other one.

“Achiral” Structures Are Superimposable (they will also a plane of symmetry) When the mirror image of an achiral structure is rotated, the structure is aligned with its initial structure. its mirror image is superimposable. A carbon is “achiral” if it is NOT attached to 4 different groups.

How can you tell if a molecule is chiral or achiral? To be chiral, a molecule must contain a chiral carbon. What’s a chiral carbon? A carbon is chiral if it is bonded to FOUR different atoms or groups!

Chirality practice Identify each as a chiral or achiral compound. A. B. C. chiral chiral achiral

A carbon is chiral if it is bonded to FOUR different atoms or groups! Indicate whether each C is chiral or achiral. * *

A carbon is chiral if it is bonded to FOUR different atoms or groups! Find the chiral carbons below: This is the only chiral carbon in this molecule. Two identical groups, so this is achiral; no chiral carbon here This molecule is achiral (no chiral Cs) This molecule is achiral (no chiral Cs) This molecule contains ONE chiral carbon.

* * * How many chiral carbon atoms are there in this molecule? There are only 3 chiral carbon atoms.

None  ! How many chiral carbons are in glycerol? Chapter 14, Unnumbered Figure 1, Page 525 None  !

A simplified way to draw tetrahedron Fischer Projections A simplified way to draw tetrahedron A Fischer projection is a two-dimensional representation of a molecule. uses vertical lines for bonds that go back. uses horizontal lines for bonds that go forward. Fischer projections can also be written for compounds that have more than one chiral center as you will see in Carbs.

Fischer Projections Ball and stick model wedge and dash drawing Fischer projection

Visualizing Fischer Projections (nonsuperimposible mirror images) More important in Carbs really… This is “D-fructose” because this Fisher Projection shows the highest # chiral carbon with the –OH on the right instead of the left side. Enantiomers (nonsuperimposible mirror images)

Drawing Fischer Projections For compounds with two or more chiral carbons, the designation as a D or L isomer is determined by the position of the –OH group attached to the chiral carbon farthest from the carbonyl group.

Learning Check Identify the following as a D or L isomer.

Solution Identify the following as a D or L isomer. The –OH group is on the right, it is a D isomer.

More on carbohydrates in the next class! 

Acetals and Hemiacetals Hemiacetals are carbon atoms that contain a hydroxyl group –OH and an alkoxy group –OR. are formed when an alcohol adds to an aldehyde or ketone in the presence of an acid catalyst. react with a second alcohol molecule to produce an acetal, a carbon with two alkoxy groups –OR. Hemiacetal acetal