MED-108 Organic Chemistry Alcohols 2 PDF

MED-108 Organic Chemistry Alcohols 2 LOBs covered Discuss methods of preparation of alcohols Identify reactants and products of alcohol reactions Making Alcohols - Grignard Reagents How do we make a Grignard reagent? Characteristics of Grignard Reagent Electronic structure is important Figure Explan...

MED-108 Organic Chemistry Alcohols 2 LOBs covered Discuss methods of preparation of alcohols Identify reactants and products of alcohol reactions Making Alcohols - Grignard Reagents How do we make a Grignard reagent? Characteristics of Grignard Reagent Electronic structure is important Figure Explanations for Revision Since Mg is less electronegative than C, when a Mg-C bond is made, electron density flows towards the C atom, making it δ-. This partially negative C atom can now attack a δ+ carbon and make a C-C bond. Making C-C bonds in organic synthesis is very difficult, thus Grignard reagents are very useful synthetically. In the second diagram, the δ- C atom from the Grignard reagent attacks a δ+ C atom in the carbonyl compound (ketone), making a C-C bond. When this happens, the C=O bond breaks and is converted to a C-O bond, and the O atom becomes negatively charged. Addition of an acid (H+) to this, will protonate the negative O atom, forming an alcohol. Alcohols from Grignard Reagents Additional Notes for Revision Addition of formaldehyde H-CHO to a Grignard reagent forms a primary alcohol Addition of an aldehyde (R-CHO) other than formaldehyde to a Grignard reagent will lead to the formation of a secondary alcohol Addition of a ketone to a Grignard reagent will lead to the formation of a tertiary alcohol More Examples Limitations – Problems Water destroys a Grignard reagent forming an alkane A similar thing can happen if there is a proton-donating group on another part of the Grignard reagent – -OH, -NH, -SH, -COOH – The proton (H) attacks the C bonded to the Mg atom, kicking MgBr off Limitations – Problems If a carbonyl group is present on another part of the Grignard reagent, there will be a self-reaction forming a cyclic compound The δ- C atom from the Grignard reagent part, attacks the δ+ C atom from the carbonyl group and makes a C-C bond with it. This causes the carbon chain to wrap around forming a ring compound, while the MgBr part is kicked off While this is a limitation, it can also serve as a useful synthetic tool for rings Alcohols Chemical Reactions Chemical Reactions of Alcohols Fischer Esterification Alcohol + Carboxylic Acid produces Ester How does the reaction take place? Examples 5-Minute Break Oxidation of Alcohols Alcohols are oxidized to carbonyl compounds (Carbonyl compounds are reduced to alcohols) Oxidizing agents KMnO4 CrO3 Na2Cr2O7 Alcohol Oxidation Primary alcohol → aldehyde → carboxylic acid (usually cannot halt the oxidation) Secondary alcohol → ketone Tertiary alcohol → resistant to oxidation (Tertiary alcohols will be oxidized to ketones under very harsh conditions) For this course we assume that ketones cannot be further oxidized Primary Alcohol Partial Oxidation One can halt the oxidation of a primary alcohol to an aldehyde by using a specialty oxidizing agent Pyridinium chlorochromate (PCC) Examples Dehydration of Alcohols Alcohol + dehydrating agent → alkene + water Dehydrating agents H2SO4 / H2O (tertiary alcohols) POCl3 / pyridine (primary & secondary alcohols) Pyridine (base) Example of Alcohol Dehydration Ethanol can be dehydrated to ethylene The acid is employed as a catalyst It makes –OH a better leaving group Additional Explanations for Revision Ethanol can be dehydrated to ethylene Since the C-O bond is quite strong, the –OH group is not a good leaving group. If we protonate the –OH group by adding an acid, then it becomes a good leaving group, giving a stable water molecule and a carbocation. Using a strong base to abstract a H atom leads to the formation of a pi bond (alkene) So, in essence, we remove the –OH group, and a H from an adjacent C atom. The net effect is removal of a water molecule - dehydration Multiple Alkene Products Often, more than one alkene can be produced Multiple Alkene Products What is the main difference between the two alkene products? Zaitsev’s Rule In the elimination of HX (or HOH) from an alkyl halide (or alcohol), the more highly substituted alkene dominates the product mixture More highly substituted means having more non-H groups connected to the alkene C atoms WATCH: https://www.youtube.com/watch?v=iJN4Uc1BVbs Alcohol Dehydration Often, cis and trans alkene products can be formed Summary for Revision Grignard reagents are formed when an alkyl halide is treated with magnesium powder in very dry ether. These reagents are useful for the formation of primary, secondary and tertiary alcohols. Reacting a Grignard reagent with formaldehyde will give a primary alcohol. Reaction with any other aldehyde will produce a secondary alcohol. Reaction with a ketone will produce a tertiary alcohol. Grignard reagent have limitations – see slides for more detail. Alcohols react with carboxylic acids to form esters. Alcohols can be oxidized readily. Primary alcohols are oxidized to carboxylic acids, through an aldehyde intermediate. Secondary alcohols oxidize to ketones. Ketones cannot easily oxidize further. Primary alcohols can oxidize to aldehydes (and not to carboxylic acids) by using PCC. Alcohols can be dehydrated, forming alkenes. Sometimes dehydration of alcohols leads to the formation of a mixture of alkenes. In this case, the major product is the most highly substituted alkene (Zaitsev’s Rule).