Chem 150 Unit 8 - Organic Molecules III Alcohols, Thiols, Ethers, Aldehydes and Ketones In this unit we continue surveying some of the families of organic molecules that play important roles in biochemistry; looking both at their physical and chemical properties. The Group VIA elements, oxygen and sulfur, typically form two covalent bonds to attain a filled valence shell. The families that include oxygen and sulfur with two single bonds include alcohols C-O-H, ethers C-O-C, thiols C-S-H, sulfides C-S-C and disulfides C-S-S-C. We will also look at two more important carbonyl containing functional groups, aldehydes and ketones.

Introduction The organic groups covered in this Unit all have important biological roles Alcohols Triglycerides Amino acids and proteins Ethers Biologically active molecules Thiols Odorants Sulfides Ketones Carbohydrates and metabolic intermediates Aldehydes

Introduction Alcohols were first encountered back in Unit 2 Alcohols comprise a hydroxyl group (-OH) attached to an alkane-type carbon atom.

Introduction Ethers Ethers have an oxygen attached to two alkane-type carbon atoms.

Introduction Sulfur containing functional groups Sulfur, like oxygen, is a Group VIA element Sulfur forms functional groups which are analogous to some of the groups formed by oxygen.

Introduction Thiol Thiols look similar to alcohols and comprise a sulfhydryl (also called mercaptan) group (-SH) bonded to an alkane- type carbon.

Introduction Sulfides Sulfides look similar to ethers and contain a sulfur atom that is bonded to two alkane-type carbon atoms.

Introduction Disulfides Disulfides look similar to a sulfide, but contain two sulfur atoms that are bonded to each other and to two alkane- type carbon atoms.

Introduction Ketones Ketones are a carbonyl containing functional group in which the carbonyl carbon is bonded to two other carbon atoms.

Introduction Ketones in the news; Diacetyl http://www.usatoday.com/news/health/2007-10-27- diacetyl_N.htm

Introduction Aldehydes Aldehydes are a carbonyl containing functional group in which the carbonyl carbon is bonded to at least one hydrogen atom.

Question Circle and label the functional groups found in the following compounds. alcohol alkene ether ketone amine

Question Circle and label the functional groups found in the following compounds. thiol ammonium ion carboxylate disulfide sulfide alkene

Question Circle and label the functional groups found in the following compounds. alcohol aldehyde ketone ether phenol

Alcohols, Ethers, Thiols, Sulfides and Disulfides The IUPAC rules for naming alcohols Find the longest carbon chain containing the carbon to which the hydroxyl group is attached. Remove the “-e” ending and replace with “-ol” Number the carbon chain from the end closest to the hydroxyl group. Identify, name and locate any substituent groups If the hydroxyl group is being treated as a substituent group, refer to it as a “hydroxyl” group.

Alcohols, Ethers, Thiols, Sulfides and Disulfides Examples of alcohol names

Alcohols, Ethers, Thiols, Sulfides and Disulfides The IUPAC rules for naming thiols Find the longest carbon chain containing the carbon to which the sulfhydryl group is attached. Add the ending “-thiol”, without removing the “-e” Number the carbon chain from the end closest to the sulfhydryl group. Identify, name and locate any substituent groups

Alcohols, Ethers, Thiols, Sulfides and Disulfides Examples of thiol names (Common names are shown in parentheses)

Alcohols, Ethers, Thiols, Sulfides and Disulfides We will not use the IUPAC rules for naming the ethers, sulfides and disulfides. Instead of using an ending, the substituents attached to the oxygen or sulfur will be listed in front fo the family name.

Alcohols, Ethers, Thiols, Sulfides and Disulfides Examples of ether, sulfide and disulfide names

Question Name the following structures.

Alcohols, Ethers, Thiols, Sulfides and Disulfides Alcohols are also labeled according to the number of carbons that are attached to the carbon that the hydroxyl group is attached to. This will be important for predicting the products of oxidation reactions involving alcohols.

Alcohols, Ethers, Thiols, Sulfides and Disulfides The hydroxyl groups of alcohols are good hydrogen bonding donors and acceptors

Alcohols, Ethers, Thiols, Sulfides and Disulfides The other functional groups are not as good at forming hydrogen bonds. Ethers can only accept hydrogen bonds. Sulfur has about the same electronegativity as carbon, and therefore, is non-polar. This is reflected in the boiling points and solubilities of these molecules.

Preparations of Alcohols, Ethers, Thiols and Sulfides In this unit we will be learn many new reactions. Pages 346 and 347 in Raymond contains a nice summary of all of the reactions that will will cover in this unit.

Preparations of Alcohols, Ethers, Thiols and Sulfides Alcohols, Ethers, Thiols and Sulfides can be prepared from alkyl halides using nucleophilic substitution reactions. A nucleophile is an electron rich atom or group or atoms. The halogen atom make a good leaving group. The nucleophile “attacks” that atom to which the halogen is attached and the halogen leaves. This results in the the nucleophile substituting for the leaving group.

Preparations of Alcohols, Ethers, Thiols and Sulfides Using nucleophilic substitution to prepare alcohols from alkyl halides: The OH- attacks The Cl- leaves The OH- attacks The Br- leaves The OH- attacks The I- leaves

Preparations of Alcohols, Ethers, Thiols and Sulfides Using nucleophilic substitution to prepare ethers, thiols and sulfides from alkyl halides:

Preparations of Alcohols, Ethers, Thiols and Sulfides Another way to produce alcohols is the hydration of alkenes We saw this reaction back in Unit 2

Reactions Involving Water (Unit 4) Hydration In the hydration reaction water is also split, but instead of being used to split another molecule, it is added to another molecule to produce a single product. The water it is added to either an alkene or alkyne: The hydration of an alkene produces an alcohol.

Reactions Involving Water (Unit 4) Hydration This can also be written in shorthand as: The H+ below the reaction arrow is used to indicate that this is an acid-catalyzed reaction. The shorthand is used to emphasize what happens to the key reactant.

Reactions Involving Water (Unit 4) Hydration example On an earlier slide a reaction from the Citric Acid Cycle was shown, which involved the dehydrogenation of succinic acid to produce fumaric acid. The sequent reaction in the Citric Acid Cycle is an example of a hydration reaction:

Preparations of Alcohols, Ethers, Thiols and Sulfides Another way to produce alcohols is the hydration of alkenes When we looked at hydration reactions back in Unit 2 we conveniently picked reactants that would only produce one product. It is possible to have multiple products in hydration reactions.

Preparations of Alcohols, Ethers, Thiols and Sulfides Multiple products occur whenever there are a different number of hydrogen atoms attached to the two carbons double-bonded carbons in the alkene. Markovnikov’s Rule can be used to predict which of the two products is predicted to be the major product. The hydrogen from the water in a hydration reaction is added to the double-bonded carbon atom that originally carried the most hydrogen atoms. If you consider hydrogens as a source of wealth, this can be more simply stated as “The rich get richer!”

Preparations of Alcohols ... More examples of hydration reactions:

Reactions of Alcohols and Thiols Back in Unit 4 we developed several definitions for Oxidation- Reduction Reactions.

Oxidation and Reduction (Unit 4) Ways of recognizing oxidation/reduction reactions: Oxidation and reductions always occur together Oxidation Reduction An atom loses electrons An atom gains electrons An atom gains a bond to oxygen An atom loses a bond to oxygen An atom loses a bond to hydrogen An atom gains a bond to hydrogen

Reactions of Alcohols and Thiols Back in Unit 7 we saw how the definition “loses hydrogens” could be applied to the oxidation of hydroquinones to produce quinones

Carboxylic Acids & Phenols, Other Reactions (Unit 7) The oxidation of hydroquinones is also an important biological reaction. A chemical oxidation of hydroquinones can be carried out the oxidizing agent K2Cr2O7 (potassium dichromate) The K2Cr2O7 is not acting as a base to remove 2 H+ ions, instead it is removing 2 H• atoms. It is not just the H+ ion that is removed in oxidation, but the H+ with its electrons.

Reactions of Alcohols and Thiols This same definition can also be applied to the oxidation of alcohols by potassium dichromate (K2Cr2O7). The oxidation requires that there are hydrogens to be removed on the carbon to which the hydroxyl is bound

Reactions of Alcohols and Thiols Application: Breathalyzer(http://science.howstuffworks.com/breathalyzer3.htm 1. The sulfuric acid removes the alcohol from the air into a liquid solution. 2. The alcohol reacts with potassium dichromate to produce: * chromium sulfate * potassium sulfate * acetic acid * water The silver nitrate is a catalyst,

Reactions of Alcohols and Thiols The oxidation of primary (1°) alcohols is a way for preparing aldehydes and carboxylic acids. The oxidation of secondary (2°) alcohols is a way for preparing ketones. The oxidation of tertiary (3°) alcohols does not occur because there are not hydrogens attached to the carbon to to which the hydroxyl is attached

Reactions of Alcohols and Thiols

Reactions of Alcohols and Thiols In biological reactions the coenzyme NAD+ is often used as the oxidizing agent. The NAD+ takes the electrons away from alcohols to produce aldehydes, carboxylic acids and ketones.

Reactions of Alcohols and Thiols Example The oxidation of malate to oxaloacetate that occurs in the citric acid cycle:

Reactions of Alcohols and Thiols Thiols can be oxidized to form disulfides using I2 as oxidizing agent We will see this oxidation reaction when we discuss proteins in Unit 10

Preparations of Alcohols, Ethers, Thiols and Sulfides Another reaction that we saw back in Unit 2 was the dehydration of alcohols to produce alkenes. We saw this reaction back in Unit 2

Preparations of Alcohols, Ethers, Thiols and Sulfides Like the complement hydration reaction, dehydration can also produce multiple products.

Preparations of Alcohols, Ethers, Thiols and Sulfides Multiple products occur whenever there are a different number of hydrogen atoms attached to the two carbons that are on either side of the carbon to which the hydroxyl is attached. There is a rule that can be used to predict which of the two products is predicted to be the major product. In a dehydration of an alcohol, the hydrogen will be removed from the neighboring carbon atom that carries the fewest hydrogen atoms. If you consider hydrogens as a source of wealth, and since we are removing wealth, this can be more simply stated as “The poor get poor!”

Preparations of Alcohols, Ethers, Thiols and Sulfides Examples of dehydration of alcohols

Aldehydes and Ketones Aldehydes and ketones are carbonyl containing functional group. They have an array of important roles to play in biological chemistry. We just saw how they can be prepared from the oxidation of primary and secondary alcohols. Back in Unit 7, we also saw how they can be prepared from the decarboxylation of α-keto acids and β-keto acids. aldehyde ketone

Carboxylic Acids & Phenols, Other Reactions (Unit 7) The decarboxylation of β-keto acids produces ketones The decarboxylation of α-keto acids produces aldehydes The carboxylic acid group leaves as CO2 and is replaced by a hydrogen. (Raymond’s answers to problems 10.27b and 10.31 are wrong)

Aldehydes and Ketones The IUPAC rules for naming aldehydes Find the longest carbon chain containing the carbon to which the hydroxyl group is attached. Remove the “-e” ending and replace with “-al” Number the carbon chain from the carbonyl carbon. Identify, name and locate any substituent groups Some of the smaller aldehydes have common names which are more often used than the IUPAC names.

Aldehydes and Ketones The IUPAC rules for naming ketones Find the longest carbon chain containing the carbon to which the hydroxyl group is attached. Remove the “-e” ending and replace with “-one” Number the carbon chain from end of the chain closest tothe carbonyl carbon. Identify, name and locate any substituent groups Common names are also used ketones The names of the two substituent groups connected to the carbonyl carbon are listed and followed by the family name ketone.

Aldehydes and Ketones Examples of names for aldehydes and ketones

Aldehydes and Ketones Aldehydes and ketones can serve has hydrogen bond acceptors, but not donors. This means that they cannot hydrogen bond to themselves, and so have much lower boiling points than alcohols However, they can hydrogen bond to water, so small aldehydes and ketones are soluble in water.

Question Draw structures for the following molecules: 3-Methylheptanal 3-Methy-2-pentanone Methyl s-butyl ketone

Oxidation of Aldehydes We have already seen how aldehydes and alcohols can be oxidized to carboxylic acids with K2Cr2O7

Oxidation of Aldehydes Aldehydes can also be oxidized with the copper(II) ion (Cu2+) This reaction oxidizes aldehydes, but not alcohols. The Cu2+ ion forms a clear blue solution The Cu+ that is produced in the reaction forms an orange/red precipitate.

Oxidation of Aldehydes Aldehydes can also be oxidized with the copper(II) ion (Cu2+) The reaction is called the Benedict’s reaction, and has been used for years in a clinical setting to test for the presence of glucose in the urine. Cu2+ Cu2+ + Cu+ Cu+

Reduction of Aldehydes and Ketones In Unit 4 we saw how H2 could be used to reduce alkenes to alkanes in the hydrogenation reaction. Because this reaction involves adding hydrogens to a molelcule, it is a reduction reaction.

Oxidation and Reduction (Unit 4) Hydrogenation Another type of oxidation/reduction reaction is the hydrogenation reaction: In this example, an alkene is reduced to an alkane. This is considered reduction, because the hydrogen is bringing in additional electrons to the molecule. The alkane that is produced in this reaction is considered “saturated” because it can no longer absorb any more hydrogen atoms. Show the fumarate reaction using FAD Show the alcohol dehydrogenase eaction using NADH Reactions with water hyrolysis of ester with acid hydrolysis of ester with base hydration reaction dehydration reactions unsaturated saturated

Oxidation and Reduction (Unit 4) Often chemist use a shorthand method of writing equations like these: The equation shown on the previous slide can be written as follows: One of the reactants, H2, is placed above the reaction arrow Technically, this equation is no longer balanced The shorthand method of writing a chemical equation is used to emphasize what happens to a key component of the reaction In this case it is the alkene. Show the fumarate reaction using FAD Show the alcohol dehydrogenase eaction using NADH Reactions with water hyrolysis of ester with acid hydrolysis of ester with base hydration reaction dehydration reactions

Reduction of Aldehydes and Ketones The same reaction can also be used to reduce aldehydes and ketones to alcohols:

Reduction of Aldehydes and Ketones In biochemistry, NADH + H+ is used instead of H2 The reduction of a ketone containing steroid by the enzyme Hydroxsteroid dehydrogenase.

Reactions of Alcohols with Aldehydes and Ketones Aldehydes and ketones can react with alcohols to form hemiacetals, hemiketals, acetals and ketals. Theses reactions will become in important in the next unit when we talk about carbohydrates. This is because carbohydrates are rich in aldehydes, ketones and alcohols

Reactions of Alcohols with Aldehydes and Ketones The first reaction, which is similar to the reduction of aldehydes and ketones, involves adding an alcohol across the carbonyl to form a hemiacetal (from aldehydes) or a hemiketal (from ketones).

Reactions of Alcohols with Aldehydes and Ketones Hemiacetal and hemiketal formation is catalyzed by acids.

Reactions of Alcohols with Aldehydes and Ketones As we will see with the carbohydrates, the carbonyl group and the alchohol that react can come from the same molecule. This will produce a ring molecule.

Reactions of Alcohols with Aldehydes and Ketones A hemiacetal or hemiketal can react with a second alcohol to form an acetal or ketal. This is a substitution reaction and produces an water molecule:

Reactions of Alcohols with Aldehydes and Ketones Sometimes the two reactions are combined into a single reaction equation:

Question Complete the following reaction:

Question Draw the structure of the hemiacetal that can form from this molecule:

The End