1. 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?
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2. 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
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3. 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
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4. 12.5 Retrosynthetic Analysis
We only learned one method to synthesize an alkyne
Review the regioselectivity and stereoselectivity in each step
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Klein, Organic Chemistry 1e

5. 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?
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6. 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
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7. 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?
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8. 12.5 Retrosynthetic Analysis
In the full retrosynthetic analysis, so far we have the last two steps worked out
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9. 12.5 Retrosynthetic Analysis
Recall that we used this method previously for converting alkenes to alkynes
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10. 12.5 Retrosynthetic Analysis
One step remains in the analysis, so we can work in the forward direction
Why is the Ts group necessary?
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11. 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. 12.5 Retrosynthetic Analysis
Perform a retrosynthetic analysis for the conversion below
Copyright 2012 John Wiley & Sons, Inc.

13. 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.

14. 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.

15. 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.

16. 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.

17. 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.

18. 13.1 Alcohols and Phenols Alcohols possess a hydroxyl group (-OH)
Hydroxyl groups are extremely common in natural compounds
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19. 13.1 Alcohols and Phenols Hydroxyl groups in natural compounds
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20. 13.1 Alcohols and Phenols
Phenols possess a hydroxyl group directly attached to an aromatic ring
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21. 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.

22. 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.

23. 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.

24. 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.

25. 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.

26. 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?
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27. 13.1 Alcohols Nomenclature
When an –OH group is attached to a benzene ring, the parent name is phenol
Practice with SkillBuilder 13.1
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28. 13.1 Alcohols Nomenclature
Name the following molecule
Draw the most stable chair conformation for (cis)-1-isopropyl-1,4-cyclohexadiol
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29. 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.

30. 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.

31. 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
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32. 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
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33. 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.

34. 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.

35. 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.

36. 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.

37. Study Guide for Sections 12.5-12.6, 13.1
DAY 4, Terms to know:
Sections , geminal, vicinal, retrosynthetic arrow, tosyl, hydroxyl, phenol group, hydrophobic, hydrophilic
DAY 4, Specific outcomes and skills that may be tested on exam 1:
Sections , 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.

38. 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
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.

39. Prep for Day 5 Must Watch videos: Other helpful videos:
(alcohol redox, FLC)
(Grignards, FLC)
(alcohol reactions, FLC)
(alcohol preparation, Khan)
(diol prep, Josh)
(protection of alcohols, Khan)
Other helpful videos:
(alcohol preparations, Roxi)
(naming alcohols, Leah)
(alcohols, UC-Irvine) watch first 16 minutes
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