Islamic University in Madinah Department of Chemistry CH1

Islamic University in Madinah Department of Chemistry CH-1 Organic Chemistry-2 Alcohols from Carbonyl Compounds Oxidation-Reduction & Organometallic Compounds Prepared By Prof Dr. Abdelfattah Haikal & Dr. Khalid Ahmad Shadid

Structure & Nomenclature v Alcohols have a hydroxyl (–OH) group bonded to a saturated carbon atom (sp 3 hybridized) 1 o 2 o Ethanol 2 -Propanol (isopropyl alcohol) 3 o 2 -Methyl 2 -propanol (tert-butyl alcohol)

Phenols • Compounds that have a hydroxyl group attached directly to a benzene ring

Ethers • The oxygen atom of an ether is bonded to two carbon atoms

Physical Properties of Alcohols and Ethers have boiling points that are roughly comparable with those of hydrocarbons of the same molecular weight (MW) v Alcohols have much higher boiling points than comparable ethers or hydrocarbons v

v For example v Alcohol molecules can associate with each other through hydrogen bonding, whereas those of ethers and hydrocarbons cannot

v Water solubility of ethers and alcohols • Both ethers and alcohols are able to form hydrogen bonds with water • Ethers have solubilities in water that are similar to those of alcohols of the same molecular weight and that are very different from those of hydrocarbons • The solubility of alcohols in water gradually decreases as the hydrocarbon portion of the molecule lengthens; long-chain alcohols are more “alkane-like” and are, therefore, less like water

v Physical Properties of Ethers Name Formula mp (o. C) bp (o. C) (1 atm)

v Physical Properties of Alcohols Name Formula * Water solubility (g/100 m. L H 2 O) mp (o. C) bp (o. C) (1 atm) *

Diethyl Ether v Diethyl ether is a very low boiling, highly flammable liquid v Most ethers react slowly with oxygen by a radical process called autoxidation to form hydroperoxides and peroxides

v v Step 1 Step 2 Hydrogen abstraction adjacent to the ether oxygen occurs readily

v Step 3 a A hydroperoxide or v Step 3 b Hydroperoxides and peroxides can be explosive A peroxide

Synthesis of Alcohols from Alkenes Acid-catalyzed Hydration of Alkenes v H ⊕

Reactions of Alcohols v The reactions of alcohols have mainly to do with the following: • The oxygen atom of the –OH group is nucleophilic and weakly basic • The hydrogen atom of the –OH group is weakly acidic • The –OH group can be converted to a leaving group so as to allow substitution or elimination reactions

C–O & O–H bonds of an alcohol are polarized v Protonation of the alcohol converts a poor leaving ⊖ group (HO ) into a good one (H 2 O)

v Once the alcohol is protonated substitution reactions become possible The protonated –OH group is a good leaving group (H 2 O)

Alcohols as Acids v Alcohols have acidities similar to that of water p. Ka Values for Some Weak Acids Acid p. Ka CH 3 OH 15. 5 H 2 O 15. 74 CH 3 CH 2 OH 15. 9 (CH 3)3 COH 18. 0

v Relative Acidity H 2 O & alcohols are the strongest acids in this series Increasing acidity v Relative Basicity ⊖ HO is the weakest acid in this series Increasing basicity

Conversion of Alcohols into Alkyl Halides • HX (X = Cl, Br, I) • PBr 3 • SOCl 2

v Examples

Alkyl Halides from the Reaction of Alcohols with Hydrogen Halides v The order of reactivity of alcohols • 3 o v > 2 o > 1 o < methyl The order of reactivity of the hydrogen halides • HI > HBr > HCl (HF is generally unreactive)

Mechanisms of the Reactions of Alcohols with HX Secondary, tertiary, allylic, and benzylic alcohols appear to react by a mechanism that involves the formation of a carbocation v Step 1 v

v Step 2 v Step 3

v Primary alcohols and methanol react to form alkyl halides under acidic conditions by an SN 2 mechanism

v Reaction of alcohols with SOCl 2 • SOCl 2 converts 1 o and 2 o alcohols to alkyl chlorides • As with PBr 3, the reaction does not involve the formation of a carbocation and usually occurs without rearrangement of the carbon skeleton (especially if the temperature is kept below 0°C) • Pyridine (C 5 H 5 N) is often included to promote the reaction

Structure of the Carbonyl Group v Carbonyl compounds Aldehyde Carboxylic acid Ketone Ester Amide

Structure The carbonyl carbon atom is sp 2 hybridized; thus it and the three groups attached to it lie in the same plane. The bond angles between the three attached atoms are what we would expect of a trigonal planar structure; they are approximately 120 o. The bonding molecular orbital of formaldehyde (HCHO). The electron pair of the bond occupies both lobes.

Polarization and resonance structure The more electronegative oxygen atom strongly attracts the electrons of both the bond and the bond, causing the carbonyl group to be highly polarized; the carbon atom bears a substantial positive charge and the oxygen atom bears a substantial negative charge.

30 There is a large dipole moments associated with carbonyl compounds. 1/31/2015

Reactions of Carbonyl Compounds with Nucleophiles One of the most important reactions of carbonyl compounds is one in which the carbonyl compound undergoes nucleophilic addition. The carbonyl group is susceptible to nucleophilic attack because, the carbonyl carbon bears a partial positive charge. As the reaction takes place, the carbon atom undergoes a change in its geometry and its hybridization state. It goes from a trigonal planar geometry and sp 2 hybridization to a tetrahedral geometry and sp 3 hybridization.

v Two important nucleophiles: ● Hydride ions (from Na. BH 4 and Li. Al. H 4) ● Carbanions (from RLi and RMg. X) Primary alcohols can be oxidized to aldehydes, and aldehydes can be reduced to alcohols. [O] [H]

Oxidation-Reduction Reactions in Organic Chemistry v Reduction of an organic molecule usually corresponds to increasing its hydrogen content or decreasing its oxygen content decreases carboxylic acid aldehyde hydrogen content increases

v v The opposite reaction of reduction is oxidation. Oxidation involves Increasing the oxygen content of an organic molecule or decreasing its hydrogen content is oxidation lowest oxidation state highest oxidation state

v Oxidation of an organic compound may be more broadly defined as a reaction that increases its content of any element more electronegative than carbon

Alcohols by Reduction of Carbonyl Compounds Primary and secondary alcohols can be synthesized by the reduction of a variety of com pounds that contain the carbonyl group. Aldehyde (1 o alcohol) Carboxylic acid Ester (2 o alcohol) Ketone

Lithium Aluminum Hydride v Li. Al. H 4 (LAH) ● Not only nucleophilic, but also very basic ● Reacts violently with H 2 O or acidic protons (e. g. ROH) ● Usually reactions run in ethereal solvents (e. g. Et 2 O, THF) ● Reduces all carbonyl groups

38 Reductions of carboxylic acids are the most difficult, but they can be accomplished with the powerful reducing agent lithium aluminum hydride (Li. Al. H 4, abbreviated LAH). It reduces carboxylic acids to primary alcohols in excellent yields. 1/31/2015

v Examples

v Mechanism o Esters are reduced to 1 alcohols

Sodium Borohydride Aldehydes and ketones can also be reduced to alcohols by hydrogen and a metal catalyst, by sodium borohydride (Na. BH 4) v Na. BH 4 ● less reactive and less basic than Li. Al. H 4 ● can use protic solvent (e. g. ROH) ● reduces only more reactive carbonyl groups (i. e. aldehydes and ketones) but not reactive towards esters or carboxylic acids

v Examples

v Mechanism (Animation) Aldehydes are reduced to 1° alcohols & ketones are reduced to 2° alcohols

44 A Mechanism for the Reaction 1/31/2015

Overall Summary of Li. Al. H 4 and Na. BH 4 Reactivity Reduced by Li. Al. H 4 Reduced by Na. BH 4 ease of reduction

46 Problem Which reducing agent, Li. AIH 4 or Na. BH 4 would you use to carry out the following transformations? 1/31/2015

5. Organometallic Compounds v Compounds that contain carbon-metal bonds are called organometallic compounds Organometallic compounds of lithium and magnesium are of great importance in organic synthesis. Their carbon-metal bonds have considerable ionic character. The carbon atoms that is bonded to the metal atom of an organolithium or organomagnesiurn compound is a strong base and powerful nucleophile.

Preparation of Organomagnesium Compounds Organomagnesium halides were discovered by the French chemist Victor Grignard in 1900. Grignard received the Nobel Prize for his discovery in 1912, and they are now called Grignard reagents in his honor. Grignard reagents have great use in organic synthesis. Grignard reagents are usually prepared by the reaction of an organic halide and magnesium metal in an ether solvent. v Order of reactivity of RX ● RI > RBr > RCl

v Example

50 Preparation of Organomagnesium Compounds Reactions with Compounds Containing Acidic Hydrogen Atoms Grignard reagents and Organolithium compounds are very strong bases. They react with any compound that has a hydrogen attached to an electronegative atom such as oxygen, nitrogen, or sulfur. 1/31/2015

Reactions of Organolithium and Organomagnesium Compounds Reactions with Compounds Containing Acidic Hydrogen Atoms

v v Grignard reagents are very strong bases Examples ● As base

v Examples ● As base

v Examples ● As base A good method for the preparation of alkynylmagnesium halides

Reactions of Grignard Reagents with Epoxides (Oxiranes) Not only are Grignard reagents strong bases, they are also powerful nucleophiles. T attack at a saturated carbon when they react with oxiranes to give primary alcohols. The nucleophilic alkyl group of the Grignard reagent attacks the partially positive carbon of the oxirane ring. Because it is highly strained, the ring opens, and the reaction leads to the salt of a primary alcohol.

v Via SN 2 reaction

Alcohols from Grignard Reagents Grignard additions to carbonyl compounds are especially useful because they can be used to prepare primary, secondary, or tertiary alcohols. 1. Grignard Reagents React with Formaldehyde to Give a Primary Alcohol. 2. Grignard Reagents React with All Other Aldehydes to Give Secondary Alcohols

3. Grignard Reagents React with Ketones to Give Tertiary Alcohols 4. Esters React with Two Molar Equivalents of a Grignard Reagent to Form Tertiary Alcohols. The product is a tertiary alcohol with two identical alkyl groups, groups that correspond to the alkyl portion of the Grignard reagent

v R = alkyl, R’ = H (higher aldehydes) o ● 2 alcohol (Animation)

v R, R’ = alkyl (ketone) o ● 3 alcohol

61 1/31/2015

62 GOOD LUCK 1/31/2015