12.5 Retrosynthetic Analysis For more challenging, complex multi-step syntheses, it is often helpful to work backwards (retro) in our analysis, although the same basic analysis is performed Perform a retrosynthetic analysis for the reaction below Analyze the structure of the reactant and product. What functional groups are we dealing with? Copyright 2012 John Wiley & Sons, Inc.

12.5 Retrosynthetic Analysis Perform a retrosynthetic analysis for the reaction below Asses HOW the carbon skeleton has changed. In this specific case, the carbon skeleton is not changing Copyright 2012 John Wiley & Sons, Inc.

12.5 Retrosynthetic Analysis Perform a retrosynthetic analysis for the reaction below Work backwards: focus on the last step in the synthesis Asses HOW the functional groups have changed. We want to make an alkyne, so what reactions do we know that can be used to make an alkyne? – see next slide Copyright 2012 John Wiley & Sons, Inc.

12.5 Retrosynthetic Analysis We only learned one method to synthesize an alkyne Review the regioselectivity and stereoselectivity in each step Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e

12.5 Retrosynthetic Analysis The last step in the synthesis must involve a geminal dihalide WHY not a vicinal dihalide? How would a vicinal dihalide be made? Copyright 2012 John Wiley & Sons, Inc.

12.5 Retrosynthetic Analysis A retrosynthetic arrow is used by chemists to show the sequence of reactions in the reverse direction Now, let’s continue the analysis by working another step backwards Copyright 2012 John Wiley & Sons, Inc.

12.5 Retrosynthetic Analysis Analyze the structure of the reactant and product. Do we know of a method to synthesize a geminal dihalide? Yes, we can use an addition reaction What reagents do we need? Copyright 2012 John Wiley & Sons, Inc.

12.5 Retrosynthetic Analysis In the full retrosynthetic analysis, so far we have the last two steps worked out Copyright 2012 John Wiley & Sons, Inc.

12.5 Retrosynthetic Analysis Recall that we used this method previously for converting alkenes to alkynes Copyright 2012 John Wiley & Sons, Inc.

12.5 Retrosynthetic Analysis One step remains in the analysis, so we can work in the forward direction Why is the Ts group necessary? Copyright 2012 John Wiley & Sons, Inc.

12.5 Retrosynthetic Analysis Review the proposed steps to make sure that the regioselectivity and stereoselectivity in each step lead to the desired product Practice with SkillBuilder 12.4 Copyright 2012 John Wiley & Sons, Inc.

12.5 Retrosynthetic Analysis Perform a retrosynthetic analysis for the conversion below Copyright 2012 John Wiley & Sons, Inc.

12.6 Practical Tips To build a molecule, you must be able to choose the right tools for the job It will be helpful if you create a list of tools and categorize them into two sets of reactions Reactions that alter the carbon skeleton – see section 12.3 Reactions that alter the functional groups – see section 12.2 As we learn more reactions, expand your list Copyright 2012 John Wiley & Sons, Inc.

12.6 Create Your Own Problems A great way to practice syntheses is to design your own problems Start with a relatively simple reactant compound Choose a set of reagents to change the compound’s carbon skeleton or functional groups, and predict the structure of the product Repeat step 2 a few more times Take out all of the intermediates and reagents so you don’t give the answer away Swap problems with a classmate to practice more Copyright 2012 John Wiley & Sons, Inc.

12.6 Create Your Own Problems This process will help you to think about syntheses in new ways Let’s work through an example Start with a relatively simple reactant compound. Let’s start with acetylene Choose a set of reagents to change the compound’s carbon skeleton or functional groups, and predict the structure of the product Copyright 2012 John Wiley & Sons, Inc.

12.6 Create Your Own Problems Repeat step 2 a few more times Take out all of the intermediates and reagents so you don’t give the answer away Swap problems with a classmate Copyright 2012 John Wiley & Sons, Inc.

12.6 Create Your Own Problems There will often be more than one way to solve a synthesis problem In general, a chemists goal is to find the most facile synthesis generally having the fewest steps Copyright 2012 John Wiley & Sons, Inc.

13.1 Alcohols and Phenols Alcohols possess a hydroxyl group (-OH) Hydroxyl groups are extremely common in natural compounds Copyright 2012 John Wiley & Sons, Inc.

13.1 Alcohols and Phenols Hydroxyl groups in natural compounds Copyright 2012 John Wiley & Sons, Inc.

13.1 Alcohols and Phenols Phenols possess a hydroxyl group directly attached to an aromatic ring Copyright 2012 John Wiley & Sons, Inc.

13.1 Alcohols Nomenclature Alcohols are named using the same procedure we used in Chapter 4 to name alkanes with minor modifications Identify the parent chain, which should include the carbon that the –OH is attached to Identify and Name the substituents Assign a locant (and prefix if necessary) to each substituent. Give the carbon that the –OH is attached to the lowest number possible List the numbered substituents before the parent name in alphabetical order. Ignore prefixes (except iso) when ordering alphabetically The –OH locant is placed either just before the parent name or just before the -ol suffix Copyright 2012 John Wiley & Sons, Inc.

13.1 Alcohols Nomenclature Alcohols are named using the same procedure we used in Chapter 4 to name alkanes with minor modifications Identify the parent chain Copyright 2012 John Wiley & Sons, Inc.

13.1 Alcohols Nomenclature Alcohols are named using the same procedure we used in Chapter 4 to name alkanes with minor modifications Assign a locant (and prefix if necessary) to each substituent. Give the carbon that the –OH is attached to the lowest number possible taking precedence over C=C double bonds Copyright 2012 John Wiley & Sons, Inc.

13.1 Alcohols Nomenclature Alcohols are named using the same procedure we used in Chapter 4 to name alkanes with minor modifications The –OH locant is placed either just before the parent name or just before the -ol suffix R or S configurations should be shown at the beginning of the name Copyright 2012 John Wiley & Sons, Inc.

13.1 Alcohols Nomenclature For cyclic alcohols, the –OH group should be on carbon 1, so often the locant is assumed and omitted Common names for some alcohols are also frequently used Copyright 2012 John Wiley & Sons, Inc.

13.1 Alcohols Nomenclature Like halides, alcohols are often classified by the type of carbon they are attached to WHY do we use these classifications? Copyright 2012 John Wiley & Sons, Inc.

13.1 Alcohols Nomenclature When an –OH group is attached to a benzene ring, the parent name is phenol Practice with SkillBuilder 13.1 Copyright 2012 John Wiley & Sons, Inc.

13.1 Alcohols Nomenclature Name the following molecule Draw the most stable chair conformation for (cis)-1-isopropyl-1,4-cyclohexadiol Copyright 2012 John Wiley & Sons, Inc.

13.1 Commercially Important Alcohols Methanol (CH3OH) is the simplest alcohol With a suitable catalyst, about 2 billion gallons of methanol is made industrially from CO2 and H2 every year Methanol is quite poisonous, but it has many uses Solvent Precursor for chemical syntheses Fuel Copyright 2012 John Wiley & Sons, Inc.

13.1 Commercially Important Alcohols Ethanol (CH3CH2OH) has been produced by fermentation for thousands of years. HOW? About 5 billion gallons of ethanol is made industrially from the acid-catalyzed hydration of ethylene every year Ethanol has many uses Solvent, precursor for chemical syntheses, fuel Human consumption – ethanol suitable for drinking is heavily taxed. Ethanol used for purposes other than drinking is often denatured. WHY? Is it poisonous? Copyright 2012 John Wiley & Sons, Inc.

13.1 Commercially Important Alcohols Isopropanol is rubbing alcohol. Draw its structure Isopropanol is made industrially from the acid-catalyzed hydration of propylene Isopropanol is poisonous, but it has many uses Industrial solvent Antiseptic Gasoline additive Copyright 2012 John Wiley & Sons, Inc.

13.1 Physical Properties of Alcohols The –OH of an alcohol can have a big effect on its physical properties Compare the boiling points below Explain the differences Copyright 2012 John Wiley & Sons, Inc.

13.1 Physical Properties of Alcohols Because they can H-bond, hydroxyl groups can attract water molecules strongly Alcohols with small carbon chains are miscible in water (they mix in any ratio). WHY? Alcohols with large carbon chains do not readily mix with water Copyright 2012 John Wiley & Sons, Inc.

13.1 Physical Properties of Alcohols Do hydrophobic groups repel or attract water? WHY are molecules with large hydrophobic groups generally insoluble in water? Alcohols with 3 or less carbons are generally water miscible Alcohols with more than 3 carbons are not miscible, and their solubility decreases as the size of the hydrophobic group increases Copyright 2012 John Wiley & Sons, Inc.

13.1 Physical Properties of Alcohols The potency as an anti-bacterial agent for an alcohol depends on the size of the hydrophobic group To kill a bacterium, the alcohol should have some water solubility. WHY? To kill a bacterium, the alcohol should have a significant hydrophobic region. WHY? Copyright 2012 John Wiley & Sons, Inc.

13.1 Physical Properties of Alcohols Hexylresorcinol is used as an antibacterial and as an antifungal agent It has a good combination of hydrophobic and hydrophilic regions It has significant water solubility Its nonpolar region helps it to pass through cell membranes Practice with conceptual checkpoint 13.3 Copyright 2012 John Wiley & Sons, Inc.

Study Guide for Sections 12.5-12.6, 13.1 DAY 4, Terms to know: Sections 12.5-12.6, 13.1 geminal, vicinal, retrosynthetic arrow, tosyl, hydroxyl, phenol group, hydrophobic, hydrophilic DAY 4, Specific outcomes and skills that may be tested on exam 1: Sections 12.5-12.6, 13.1 Given some reagents and/or intermediates, be able to solve syntheses longer than 3 steps Be able to explain region- and stereo- outcomes predicted in your syntheses Be able to perform a retrosynthetic analysis to design a synthesis for a specific product Be able to name alcohols and phenols Given a name, be able to draw structures for alcohols and phenols Be able to describe the types of intermolecular attractions that could exist between two molecules and describe how that affects their physical properties such as boiling point, solubility, etc.

Extra Practice Problems for Sections 12.5-12.6, 13.1 Complete these problems outside of class until you are confident you have learned the SKILLS in this section outlined on the study guide and we will review some of them next class period. 12.13 12.16 12.18 12.20 12.24 12.26 13.1 13.2 13.30 13.31 13.32 For the quiz on day 5, to earn credit, you must write two synthesis problems that are at least three step synthesis and hand them in. I will review them, and I will select some to use as quiz questions for individuals. This quiz will be worth 10 points instead of the usual 5 points.

Prep for Day 5 Must Watch videos: Other helpful videos: https://www.youtube.com/watch?v=CLzd8G9EDaY (alcohol redox, FLC) https://www.youtube.com/watch?v=fWGlMCJ8XQA (Grignards, FLC) https://www.youtube.com/watch?v=qy9WKwf8ltc (alcohol reactions, FLC) https://www.youtube.com/watch?v=ad5e-jy-eqs (alcohol preparation, Khan) https://www.youtube.com/watch?v=03GNijdNvo0 (diol prep, Josh) https://www.youtube.com/watch?v=KsdZsWOsB84 (protection of alcohols, Khan) Other helpful videos: https://www.youtube.com/watch?v=XKGlMS_3-Ao (alcohol preparations, Roxi) https://www.youtube.com/watch?v=HuW3Rp1bj2k (naming alcohols, Leah) http://ocw.uci.edu/lectures/chemistry_51b_organic_chemistry_lec_06.html (alcohols, UC-Irvine) watch first 16 minutes Read Sections 13.2-13.7