Ch. 10 - Addition ReactionsSee all chapters
All Chapters
Ch. 1 - A Review of General Chemistry
Ch. 2 - Molecular Representations
Ch. 3 - Acids and Bases
Ch. 4 - Alkanes and Cycloalkanes
Ch. 5 - Chirality
Ch. 6 - Thermodynamics and Kinetics
Ch. 7 - Substitution Reactions
Ch. 8 - Elimination Reactions
Ch. 9 - Alkenes and Alkynes
Ch. 10 - Addition Reactions
Ch. 11 - Radical Reactions
Ch. 12 - Alcohols, Ethers, Epoxides and Thiols
Ch. 13 - Alcohols and Carbonyl Compounds
Ch. 14 - Synthetic Techniques
Ch. 15 - Analytical Techniques: IR, NMR, Mass Spect
Ch. 16 - Conjugated Systems
Ch. 17 - Aromaticity
Ch. 18 - Reactions of Aromatics: EAS and Beyond
Ch. 19 - Aldehydes and Ketones: Nucleophilic Addition
Ch. 20 - Carboxylic Acid Derivatives: NAS
Ch. 21 - Enolate Chemistry: Reactions at the Alpha-Carbon
Ch. 22 - Condensation Chemistry
Ch. 23 - Amines
Ch. 24 - Carbohydrates
Ch. 25 - Phenols
Ch. 26 - Amino Acids, Peptides, and Proteins
Sections
Addition Reaction
Markovnikov
Hydrohalogenation
Acid-Catalyzed Hydration
Oxymercuration
Hydroboration
Hydrogenation
Halogenation
Halohydrin
Carbene
Epoxidation
Epoxide Reactions
Dihydroxylation
Ozonolysis
Oxidative Cleavage
Alkyne Oxidative Cleavage
Alkyne Hydrohalogenation
Alkyne Halogenation
Alkyne Hydration
Alkyne Hydroboration
Additional Practice
Thermodynamics of Addition-Elimination Equilibria
Stereospecificity vs. Stereoselectivity
Sulfonation
Oxymercuration-Reduction Full Mechanism
Hydroboration-Oxidation Full Mechanism
Alkoxymercuation
Interhalogenation
Haloether Formation
Simmons-Smith Addition Mechanism
Regiospecificity of Acid-Catalyzed Ring Openings
Anti Vicinal Dihydroxylation
Ozonolysis Full Mechanism
Ozonolysis Retrosynthesis
LiBr and Acetic Acid for Anti Vinyl Dihaldes
Addition Reagent Facts
Predicting Stereoisomers of Addition Reactions
Addition Missing Reagent
Addition Synthesis
Addition Texas Two-Step
Addition Retrosynthesis
Addition to Concave vs. Convex Rings
Johnny Betancourt

Ozonolysis is a type of weak oxidative cleavage where we cleave alkenes (double bonds) into either ketones, aldehydes or carboxylic acid using ozone.

Topic: Weak Oxidative Cleavage

The History of Ozonolysis:

Ozonolysis, or “oxidative cleavage” originated in the 1800’s with its inventor, Christian Friedrich Schönbein. The reaction also is attributed to Carl Dietrich Harries, therefore you may hear this reaction termed “Harries ozonolysis”.

You may be thinking, “Umm... Why do I need to know this?”. The answer is, well you don’t! (But in case you were wondering, now you know & can tell your friends).

Ozone Structure

It is in simplest terms using ozone, or O3 (the structure is shown above with correct formal charges) to cleave carbon-carbon double bonds (C=C) to produce various carbonyls.

2 Pathways:

1. Aldehydes (CHO), and ketones (CH3COCH3) can be formed through reductive workup. This refers to what is shown under the arrow below. Me2S is also DMS and stands for dimethyl sulfide.

Ozonolysis-RetrosynthesisOzonolysis Retrosynthesis

Now I’m sure you’re wondering, which structure was our starting material? For that answer scroll down just a bit, but first try to draw it out!

2. Carboxylic acid  (COOH, CO2H) can also be formed as well except it is through an oxidative workup step instead. H2O2 (hydrogen peroxide) is the reagent to look out for because as seen below it turns:

- Ends of alkenes with 1 –H  ≠  Aldehydes but Carboxylic Acids instead

Ozonolysis-with-Oxidative-WorkupOzonolysis with Oxidative Workup


Answer from above:

Di-substituted alkeneDi-substituted alkene

How Does Ozonolysis Work?

Now we will discuss the specifics of the mechanism of ozonolysis.

A. Reagents:

Commonly seen is the use of O3, which is ozone (structure shown above), in the presence of a reducing agent such as dimethyl sulfide (DMS, Me2S, S(CH3)2) or zinc & acetic acid (Zn/HOAc).

Therefore a full reaction may look like this:

Ozonolysis-ReactionOzonolysis Reaction

Now as we said, instead of DMS under the arrow you may also see zinc and acetic acid. Beware of the other ways “acetic acid” can be written in addition to HOAc. They are: [AcOH, CH3COOH, CH3CO2H]

This type of mechanism is referred to as ozonolysis with reductive workup.

In case you need to know:

After the reduction takes place our Zn or DMS will attach to the remaining third oxygen from our O3 that is not seen in our final product. Because of this, along with our carbonyl products we will also find DMSO (dimethyl sulfoxide) or ZnO (zinc oxide) produced as well.


Ozonolysis-MechanismOzonolysis Mechanism

DMSO is simply the blue structure you see at the top right of the image. A couple other intermediates you may see are the molozonide and the ozonide which we will discuss below.

B. Reaction Mechanism and Intermediates:

When the reaction takes place, the first intermediate you will see is called your molozonide. It is a cyclic structure containing 3 oxygen atoms connected in a row, also referred to as a 1,2,3-trioxolane.

Molozonide-IntermediateMolozonide Intermediate

This will be your unstable intermediate which will further undergo a rearrangement to form your ozonide. An ozonide is more stable than the molozonide, however it still exhibits a fair amount of instability.

Ozonide-IntermediateOzonide Intermediate

These are not isolated either and will further be reduced or oxidized depending on if you follow the “reductive workup” pathway or the “oxidative workup” pathway.

*Rudolf Criegee proposed the mechanism therefore if you hear words such as the ‘Criegee zwitterion’ or ‘Criegee intermediate’  that is why! It is referring to an intermediate that appears between the molozonide and the ozonide.

Criegee-IntermediateCriegee Intermediate

C. Products:

The products of ozonolysis will vary depending on two things: 

1) The R groups that are attached to the alkene:

     1. Ends of alkenes with –R groups on both sides =  Ketones
     2. Ends of alkenes with 1 –H =  Aldehydes
     3. Ends of alkenes with 2 –Hs (yielding single carbon fragments) =  Formaldehyde

2) Instead of a “reductive workup” with either zinc (Zn) and acetic acid (HOAc), we use an “oxidative workup” with hydrogen peroxide (H2O2).

Ozonolysis-with-Oxidative-Workup-of-Cyclic-AlkeneOzonolysis with Oxidative Workup of Cyclic Alkene

What this will do is alter our products so that any aldehydes (CHO) that were formed in our cleavage step will be oxidized into carboxylic acids (COOH).

Question: Can you guess what the product will be here? I’ll give you a hint. Cut across the double bond and add in the missing hydrogen on the red C. Then use the rule above to predict the final product. Scroll down for the answer :)


Special Ozonolysis Cases:

# 1 - Fragments

- You may sometimes hear the products of this reaction referred to as “fragments”. All this is referring to is the different molecules that were formed when we broke apart our original C-C double bond.

- For example if 2 aldehydes (CHO) were your products, you could say that 2 aldehyde fragments were formed while performing an oxidative cleavage.

- This word is more commonly used when multiple alkenes are cleaved.

#2 - Pyridine 

- Pyridine is commonly seen as a buffer when any kind of acid is generated in the reaction.

#3 - Alcohols 

- If NaBH4 (sodium borohydride) is used as the reagent during the reductive workup we will yield alcohols instead of aldehydes & ketones as seen when Zn, or DMS is used.

- This is explained much better in the video below where we focus strictly on reduction. To watch the full explanation just click here and scroll to 7:30!

Reduction-with-Sodium-BorohydrideReduction with Sodium Borohydride

# 4 - Dichloromethane

- Dichloromethane (CH2Cl2) in particular may be seen as a solvent to help with cleavage of the ozonide intermediate to yield our product.

# 5 - Triphenylphosphine

- Triphenylphosphine (PPH3, PH3P) is one of the other reagents used, just as we learned with Zn and DMS to achieve our product in a reductive workup mechanism.

Answer to above example with H2O2

Dicarboxylic-AcidDicarboxylic Acid

“I’m confused about....”

a. Which step of the mechanism is sometimes known as reductive ozonolysis?

     - The last step where we go from our ozonide to the product is known as the reductive workup. It is commonly seen more than the oxidative one. Sometimes seen to accomplish this along with DMS & Zn is PPH3 (Triphenylphosphine).

b. What is meant by the word ‘quench’?

     - Generally speaking this means to stop the reaction by getting rid of any unreacted reagents, usually with an aqueous solution. 

c. What are some of the reaction conditions? (Mainly for lab)

     - Temperature wise it is suggested to run this reaction at around -78 ̊C.

d. Are they any indicators I should know about that are used in this reaction?

     - Yes, blue usually means you are done reacting with the alkene. Also, violet can be seen along with Sudan Red III which is specifically used for special cases where multiple alkenes can react at different rates.

Just a Quick Recap:

Remember, if you see O3 + alkene these are conditions for the ozonolysis mechanism. Your product will be some form of a carbonyl, either an aldehyde, ketone, or carboxylic acid if using H2O2


Johnny Betancourt

Johnny got his start tutoring Organic in 2006 when he was a Teaching Assistant. He graduated in Chemistry from FIU and finished up his UF Doctor of Pharmacy last year. He now enjoys helping thousands of students crush mechanisms, while moonlighting as a clinical pharmacist on weekends.


Additional Problems
Which of the following gives only one organic product on ozonolysis? a) 2-hexyne b) 3-hexyne c) 2-heptyne d) 3-heptyne
Give the product, or products, including stereochemistry of the reaction of (Z)-3-methyl-2-pentene with the reagent below. If the products are a pair of enantiomers, you need to draw only one and state that the other enantiomer is formed.  O3 / S(CH3)2
All the following reactions have been reported in the chemical literature. Give the structure of the principal organic product in each case.
Circle the only compound that does NOT react with ozone:
Which of these products would result from ozonolysis of (R)-(+)-limonene, followed by reductive workup? The structure of racemic limonene is shown.
The following reactions all involve chemistry of alkenes. Fill in the box with the product(s) that are missing from the chemical reaction equations. Draw only the predominant regioisomer product or products (i.e. Markovnikov or non-Markovnikov products) and please remember that you must draw the structures of all the product stereoisomers using wedges and dashes to indicate stereochemistry. When a racemic mixture is formed, you must write "racemic" under both structures EVEN THOUGH YOU DREW BOTH STRUCTURES.
Identify the products for the following reaction below.
Draw the organic product of the following reaction, being mindful of stereochemistry. If the reaction forms two enantiomers, draw one of the two enantiomers.
Consider the structures below and answer the following questions.  e. Which compounds each form a single product on treatment with O 3 / (CH3)2S?
Propose an efficient synthesis of cyclopentanone from 1-methylcyclopentane:
What are the major products of the following reaction?
Predict the major product
Complete the following reaction by drawing the structure of the principal major product. Indicate relative stereochemistry where necessary. If there is no reaction, write NR.
What are the expected major products from the reaction sequence shown below? a) IV b) V c) I d) II e) III
What will be the major product of the following reactions? Pay careful attention to stereochemistry of the product. 
An unknown alkene gives propanal as the only product upon ozonolysis (reductive workup). When the unknown is treated with bromine in carbon tetrachloride, an optically inactive dibromide is formed, which cannot be resolved into enantiomers. Which of these alkenes is consistent with this data?
Predict the organic product(s) for the following reaction. Be sure to indicate stereochemistry when appropriate, if stereoisomers are produced draw one and state the relationship between the other stereoisomer formed. (enantiomers, diastereomers, etc.).
The following molecule undergo ozonolysis with excess ozone to give, after treatment with excess Me2S, more than one product. Show all the possible products.
The following molecule undergo ozonolysis with excess ozone to give, after treatment with excess Me2S, more than one product. Show all the possible products.
Provide the major product for each of the following alkene reactions. 
What is the expected major product of the following reaction sequence?
Predict the product:
Write the structure of the major organic product formed in the reaction of 1-pentene with each of the following:(k) Product of part (j) treated with zinc and water 
Supply Reagents:
Write the structure of the major organic product formed in the reaction of 2-methyl-2-butene with each of the following:(k) Product of part (j) treated with zinc and water 
Predict the organic product(s) of the following reaction. When appropriate, be sure to indicate stereochemistry. If more than one product is formed be sure to indicate the major product, if stereoisomers are produced in the reaction be sure to indicate the relationship between them. Draw all answers in skeletal form. 
Write the structure of the major organic product formed in the reaction of 1-methylcyclohexene with each of the following:(k) Product of part (j) treated with zinc and water 
Major product of the following reaction is:
Predict the product(s):
What is the expected major product of the reaction sequence shown below?
Draw the products form when the following alkene is treated with O3 followed by Zn, H2O. 
Predict the organic products, in any order, when the following alkene is subjected to ozonolysis with reductive work-up.
What alkyne (or diyne) yields the following oxidative cleavage products? Click the "draw structure" button to launch the drawing utility. 
Give the correct organic products, in any order, for the following ozonolysis reaction: 
Draw the organic product(s) of the following reactions, and include carbon dioxide if it is produced.
The alkene shown below is treated sequentially with ozone (O3) and zinc/acetic acid. Draw structural formula(s) for the organic product(s) formed. 
What is the product of the following reaction? 
Draw the products that are formed when the compound shown below is treated with the following reagents:1. O3, -78°C2. H2O2, H2O
Draw the correct products, in either order, for the following ozonolysis reaction:
Which is product of ozonolysis?  
Draw the major products for the following reaction.
What is the major organic product obtained from the following reaction?
Which of the following conditions and reagents were used to make this compound? Select one: