PTT 102 Organic Chemistry Alcohol & Ether Reaction of Alcohol and Ethers Mdm Khadijah Hanim Abdul Rahman

Course Outcome CO2: Ability to EXPLAIN and DIFFERENTIATE the chemical, physical properties and reactions of alcohol, ether, aldehyde, ketone and carboxylic acids

HOW ARE ALCOHOLS CLASSIFIED AND NAMED?

Alcohols – An alcohol is an organic compound with an — OH group. – The —OH functional group in alcohols is called a hydroxyl group or hydroxy function. 23.2

Alcohols 23.2

Alcohols 23.2

Alcohols 23.2

8 1. Determine the longest hydrocarbon containing the functional group: 2. The functional group suffix should get the lowest number:

9 3. When there is both a functional group suffix and a substituent, the functional group suffix gets the lowest number: 4. The chain is numbered in the direction that gives a substituent the lowest number:

10 6. If there is more than one substituent, the substituents are cited in alphabetical order: 5. The functional group substituent on a ring gets the number 1, but the functional group is not numbered in the name:

exercise

Chemical and Physical Properties Alcohols have an odor that is often described as “biting” and as “hanging” in the nasal passages. Alcohol has both non-polar alkyl groups and polar hydroxyl group. Is alcohol polar or non-polar molecules? Depends on the size of the alkyl group. As the alkyl group increases in size, becoming a more significant fraction of the alcohol, the compound become less and less soluble in water. Alcohol less than 4 carbons soluble in water. Because of hydrogen bonding, alcohols tend to have higher boiling points than comparable hydrocarbons and ethers. The boiling point of the alcohol ethanol is °C.hydrogen bondinghydrocarbonsethers Alcohols can also undergo oxidation to give aldehydes, ketones, or carboxylic acids, or they can be dehydrated to alkenes. They can react to form ester compounds, and they can (if activated first) undergo nucleophilic substitution reactionsoxidationaldehydesketones carboxylic acidsalkenesester compoundsnucleophilic substitution

Ethers What is the general structure of an ether and how are the alkyl groups of an ether named? 23.2

Ethers – The general structure of an ether is R—O—R. The alkyl groups attached to the ether linkage are named in alphabetical order and are followed by the word ether. 23.2

Ethers An ether is a compound in which oxygen is bonded to two carbon groups. 23.2

16 Nomenclature of Ethers As substituents:

Exercises CH 3 CH 2 CH 2 CH 2 CHCH 2 CH 2 CH 3 CH 3 CHOCH 2 CH 2 CHCH 3 1- propoxy-butane 2-isopropoxyhexane OCH CH 3

Physical and Chemical Properties Ether molecules cannot form hydrogen bonds with each other, resulting in a relatively low boiling points.moleculeshydrogen bonds boiling points Ethers are slightly polar. Ethers are more polar than alkenes but not as polar as alcohols, esters, or amides of comparable structure.amides Ethers in general are of low chemical reactivity, but they are more reactive than alkanesreactivityalkanes

Reaction of Alcohol and Ethers 1. Alcohol Elimination Reaction 2. Oxidation of Alcohol 3. Ether substitution reaction 4. Epoxide Reaction 5.Crown Ethers Synthesis

1. Alcohol Elimination Reaction Alcohol can undergo elimination reaction by losing an OH from one carbon and an H from adjacent carbon. Overall, this amounts to the elimination of WATER. Lost of water from a molecule is called DEHYDRATION. The product of the reaction is an ALKENE.

Dehydration of an alcohol requires an acid catalyst and heat. Sulfuric acid (H 2 SO 4 ) and Phosphoric acid (H 3 PO 4 ) are commonly used acid catalysts.

The mechanism for acid-catalyzed dehydration depends on the structure of the alcohol. Dehydration of secondary and tertiary alcohol are E1 reactions.

What is the E1 reaction? E1 reaction stand for, E=elimination and 1= unimolecular. The E1 reaction has 2 steps: In the E1 mechanism, the the first step is the loss of the leaving group, which leaves in a very slow step, resulting in the formation of a carbocation. The base then attacks a neighboring hydrogen, forcing the electrons from the hydrogen-carbon bond to make the double bond.

24 Dehydration of Secondary and Tertiary Alcohols by an E1 Pathway The acids protonates the most basic atom in the reactant. Protonation converts the very polar leaving group (OH) into a good leaving (H 2 O). Water departs, leaving behind a carbocation. A base in the reaction mixture (water is the base) removes a proton from a β carbon, forming an alkene

When acid-catalyzed dehydration leads to more than 1 elimination product, the major product will be the more substituted alkene- the 1 obtained by removing a proton from the β-carbon bonded to fewest H.

26 Because the rate-determining step in the dehydration reaction of 2° or 3° alcohol is a formation Of a carbocation intermediate, The rate of dehydration reflects the ease with which the carbocation is formed: In order to undergo dehydration, tertiary alcohols must be heated to 50 o C in 5% H 2 SO 4. secondary alcohols must be heated to about 100 o C in 75% acid primary alcohol can be dehydrated in extreme conditions, 170 o C in 95% acid

Carbocation Rearrangement Dehydration of 2° and 3° alcohols involves the formation of carbocation intermediate, so be sure to check the structure of the carbocation. Carbocation will rearrange if rearrangement produces a more stable carbocation. 27

Primary Alcohols Undergo Dehydration by an E2 Pathway Why?? Because primary carbocation are too unstable to be formed. E2 reaction :one-step process of elimination with a single transition state.transition state Any base (B: ) in the reaction mixture (ROH,ROR, H 2 O.HSO 4 - ) can remove the proton in the elimination reaction An ether is also obtained: it is the product of competing S N 2 reaction since 1° alcohol are one most likely to form substitution products in S N 2/E2 reaction

The E2 reaction E= elimination; 2= bimolecular The base (OH- ion) removes a proton from a C that is adjacent to the carbon that is bonded to the halogen. As the proton is removed, the electrons that it shared with C move toward the adjacent carbon that is bonded to the halogen. As these electrons move toward the C, the halogen leaves, taking its bonding electrons with it.

30 Primary Alcohols Undergo Dehydration by an E2 Pathway

2. Oxidation of Alcohol Reagent used to oxidize alcohols : chromic acid (H 2 CrO 4 ) Secondary alcohols : oxidized to ketones. - Recognized as oxidation because the no of C-H bonds in the reactant decreases and the no. of C-O bonds increases.

Oxidation by Chromium (VI) 32

Primary alcohols Initially oxidized to aldehydes. The reaction continue (further oxidized- no of C-O bonds increases) to carboxylic acid.

Oxidation of a primary alcohol will stop at aldehyde if PCC (pyridinium chlorochromate) is used as the oxidizing agent in solvent (CH 2 Cl). Oxidation of both 1 o and 2 o alcohol, a H is removed from C that OH is attached. The carbon bearing OH group in a 3 o alcohol is not bonded to H, so its OH group cannot be oxidized.

36 A tertiary alcohol cannot be oxidized and is converted to a stable chromate ester instead: Di-tert-Butyl Chromate No hydrogen on this carbon

Mechanism: An oxygen of chromic acid is protonated in the acidic solution The alcohol molecule displaces a molecule of water in an S N 2 reaction on chromium A base present in the reaction mixture (H2O, ROH) removes a proton from the strongly acidic spesies A base removes a proton from chromates ester in an E2 reaction, thereby forming the carbonyl compound

Exercises 3-pentanol 1-pentanol 2-methyl-2-pentanol Propose a mechanism for the chromic acid oxidation of 1-propanol to propanal.

3. Nucleophilic substitution reactions of ethers The OR group of an ether and the OH group of an alcohol have nearly the same basicity. Both groups are strong bases, so both are very poor leaving group. Consequently, ethers, like alcohols, needs to be activated before they can undergo a nucleophilic substitution reaction

40 Nucleophilic Substitution Reactions of Ethers Ethers, like alcohols, can be activated by protonation. Ethers can undergo nucleophilic substitution reactions with HBr/HI If departure of ROH creates a relatively stable carbocation, an S N 1 reaction occurs

41 Mechanism for Ether cleavage: an S N 1 reaction: 1. Protonation converts the very basic RO- leaving group into the less basic ROH leaving group. 2. The leaving group departs 3. The halide ion combines with carbocation However if departure of the leaving group would create an unstable carbocation, the leaving group cannot depart but has to be displaced by halide ion  S N 2 reaction.

Ether cleavage: an S N 2 reaction: 1.Protonation converts the very basic RO- leaving group into the less basic ROH leaving group. 2.The halide ion preferentially attacks the less sterically hindered of the 2 alkyl groups.

exercise Give the major product obtained from heating the following ether with HI CH 3 CH=CH-O-CH 2 CH 3

4. Nucleophilic substitution Reactions of Epoxides Alkene can be converted into epoxide by a peroxyacid Or by the addition of ClOH (by using Cl 2 and H 2 O) followed by HO -

Epoxides undergo substitution reaction with hydrogen halides. The mechanisms of the reaction depends on whether it is carried out under acidic or neutral/basic conditions.

Nucleophilics Substitution: Acid Conditions

47 Acid-Catalyzed Epoxide Ring Opening HBr: Protonated epoxides are so reactive that they can be opened by poor nucleophiles, such as water and alcohols, where HB+ is any acid in the solution and :B is any base. The acid protonates the oxygen atom of the epoxide The protonated epoxide undergoes back-side attack by the halide ion

If different substituent are attached to the two carbons of the protonated epoxide, and the nucleophile is something other than H 2 O, the product obtained from nucleophilic attack on the 2- position of the oxirane will be different from that obtained from nucleophilic attack on the 3- position. The major product is the one resulting from nucleophilic attack on the more substituted carbon

49 Reaction of an epoxide in the presence of methanol and acid Mechanism: Regioselectivity:

Nucleophilics Substitution: Basic/Neutral Conditions

51 When a nucleophile attacks an unprotonated epoxide, the reaction is a pure S N 2 reaction: The C-O bond does not begin to break until the carbon is attacked by the nucleophile. The nucleophile is more likely to attack the less substituted carbon because it is less sterically hindered The alkoxide ion picks up a proton from the solvent or from acid added after the reaction is over. Thus the site of nucleophilic attack on an unsymmetrical epoxide under neutral/basic conditions is different from the site of nucleophilic attack under acidic conditions Therefore:

5.Crown Ethers Synthesis Crown ethers are cyclic compounds containing several ether linkage around a central cavity A crown ether specifically binds certain metal ions or organic molecules. The crown ether is called the “host” and the species it binds is called the “guest”

Crown ethers are named [X]-Crown-Y, where X is the total no of atoms in the ring and Y is the no of oxygen atoms in the ring. Binding of Na+ and crown ethers are thru interaction of the positively charged ion with lone pair electrons of oxygen atoms that point into the cavity. Crown ethers are soluble in nonpolar solvents because the outside of the crown is composed of primarily C-H bonds.

54 Crown Ethers The ability of a host to bond only certain guests is an example of molecular recognition. The recognition of 1 molecule for another as a result of specific interactions. Because the ether linkages are chemically inert, the crown ether can bind the guest without reacting with it. The crown-guest complex is called INCLUSION COMPOUND