synthesis practice problems organic chemistry 2

Chemistry Steps

Organic Chemistry

Organic synthesis problems.

Organic Chemistry Practice Problems can be found after each topic covered in Chemistry Steps. The list of topics can be found here , and below are some examples of what you will find.

Organic Chemistry 1 Synthesis Problems

Nucleophilic substitution and elimination reactions, practice problems.

Predict the mechanism as SN1, SN2, E1 or E2 and draw the major organic product formed in each reaction. Consider any regioselectivity and stereoselectivity where applicable:

Answers and Solutions

Reactions of Alkenes Practice Problems

This is a comprehensive problem that covers the following topics and will serve as a review of all of them:

Substitution and elimination reactions.  Particularly,  substitution and elimination reactions of alcohols , the  regio – and stereochemistry of E2 reactions, and E2 reaction of cyclohexanes .

Mesylation and tosylation in Substitution and elimination reactions. 

Hydrohalogenation of alkenes according to Markovnikov’s rule .

Radical hydrohalogenation of alkenes .

Hydroboration-Oxidation of Alkenes .

Halogenation of alkenes through halohydrin formation .

Syn and anti dihydroxylation of alkenes.

Elimination reactions: Zaitsev and Hoffman products .

Ozonolysis of Alkenes.

Attempt to solve the entire problem before accessing the answers!

The  answers  will give you the structure of the  final product(s) only . Use this as a hint to determine the compounds formed after the first and second reactions.

Complete the following synthesis by adding the missing reagent(s) for each step and the structures for compound A and B:

Reactions of Alkynes Practice Problems

On the following synthetic scheme, identify the reagents, in the correct order, that you would use to achieve the following synthetic transformations. Determine the structure of compounds A and B and the major organic products resulting from the alkyne.

Organic Chemistry 2 Practice Problems

Alcohols practice problems.

Predict the major organic product(s) for the following Grignard reactions of a ketone, aldehyde, ester, carbon dioxide and an epoxide:

The Diels-Alder Reaction Practice Problems

For each Diels–Alder reaction, predict the major product(s) with correct stereochemistry when each cyclic  diene is reacted with a dienophile:

Aromatic Substitution Practice Problems

Show how each compound can be synthesized from benzene and any other organic or inorganic reagents.

The order of reactions is very important!  So, before every step,  consider the ortho – ,  para – ,  or meta directing effect  of the current group on the aromatic ring.

Devise a synthesis of each of the following compounds using an arene diazonium salt. They all require more than one step and you may select the desired regioisomer (for example the para product from an ortho, para mixture) when needed.

Aldehydes and Ketones Practice Problems

Predict the major product(s) obtained when each of the following compounds undergoes hydrolysis in the presence of an acid:

 Carboxylic Acids and Their Derivatives Practice Problems

Predict the  major organic product(s)  for each of the following reactions. They  all involve carboxylic acid derivatives  such as  esters, acid chlorides, nitriles, anhydrides, and amides . You may also need to go over the reactions covered in earlier chapters, particularly, the  Grignard  and  Gilman  reagents,  oxidizing  and  reducing   agents  and  electrophilic aromatic substitutions .

A link to each topic encountered in a given problem will be provided in the answer tab.

Alpha Carbon Chemistry – Enols and Enolates Practice Problems

This is a comprehensive practice problem  on the alpha carbon chemistry. The topics covered range from the simple halogenation reactions of enols to  multistep synthetic transformation .

To correctly answer these questions, you need to review the main principles of enolate chemistry – direct enolate alkylation, aldol condensation, crossed aldol condensation, alkylation using acetoacetic ester synthesis, malonic ester synthesis, the Stork enamine synthesis, Claisen condensation, Michael addition, and Robinson annulation.

CS Prime membership will also grant you access to multiple-choice quizzes !

If you are towards the end of your Organic 2 semester having covered most of the topics and ready for some more challenging synthesis problems – you are in the right place! In these practice problems, we will go over multistep organic synthesis.

Check also our new synthesis puzzles!

Go ahead and give it a try!

Determine the structure of each unknown in the following synthesis problems:

Keep in mind that it is rare to perform synthesis where only one product is formed and most often there is a need for isolating and purifying the desired product. So in this set of problems, you can choose a route where the target product is obtained as a mixture, even though it is desirable to design a synthesis where the yield of the target compound is in a reasonable range.

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By joining Chemistry Steps, you will gain instant access to the answers and solutions for all the Practice Problems including over 20 hours of problem-solving videos, Multiple-Choice Quizzes, Puzzles, and t he powerful set of Organic Chemistry 1 and 2 Summary Study Guides .

Check Also:

• Carboxylic Acids and Their Derivatives Practice Problems
• Acetals as Protecting Groups for Aldehydes and Ketones
• How to Choose Molecules for Doing SN2 and SN1 Synthesis-Practice Problems
• Alkene Reactions Practice Problems
• Changing the Position of a Double Bond
• Changing the Position of a Leaving Group
• Alkenes Multi-Step Synthesis Practice Problems
• Alkyne Synthesis Reactions Practice Problems
• Radical Halogenation in Organic Synthesis
• Grignard Reaction in Organic Synthesis with Practice Problems
• Ortho Para Meta Directors in Electrophilic Aromatic Substitution with Practice Problems
• Orientation in Benzene Rings With More Than One Substituent

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The following problems are meant to be useful study tools for students involved in most undergraduate organic chemistry courses.  The problems have been color-coded to indicate whether they are:

1.   Generally useful , 2.   Most likely to be useful to students in year long, rather than survey courses , 3.   Most likely to be useful only to students in courses for chemistry majors and/or honors students .

Some of these problems make use of a Molecular Editor drawing application.  To practice using this editor Click Here .

Most of these Interactive Organic Chemistry Practice Problems have been developed by Professor William Reusch. �1999 William Reusch, All rights reserved. Comments, questions and errors should be sent to [email protected] . The Virtual Text and some of the problems make use of either the CHIME plugin , or Jmol . Click on the name for information and a free copy. If possible, monitor resolutions of 1024 x 768 or 1152 x 870 should be used.

Department of Chemistry Michigan State University East Lansing, MI  48824

MCAT and Organic Chemistry Study Guides, Videos, Cheat Sheets, tutoring and more

How to Tackle Organic Chemistry Synthesis Questions

November 10, 2016 By Leah4sci 4 Comments

It's not so scary at first, think about the simple acid/base deprotonation, an alkene reaction here, another there. Before you know it, you’re drowning in dozens upon dozens of reactions!

You’re asked to ‘memorize’ each one, to know what every reactant and reagent will do. And once you have it all down, don’t forget the dozen or so exceptions to the rule.

And once you have all THAT down, let’s put them all together: when you’re given molecule A and asked to come up with all 20 steps to produce product Z!

Ok, perhaps I’m exaggerating a bit…but really, just a tiny bit!

The average Organic Chemistry 1 or 2 exam synthesis question will range from two to five steps with intermediates.

How do you keep everything you learned straight?

And more importantly, how do you sift through the hundreds of data points in your head to produce the exact steps required to achieve the desired outcome?

As a kid, I was proud to call myself a nerd. Perhaps with a bit of OCD. I always looked for trends and found patterns where they didn’t exist. Perhaps that’s why I enjoy Orgo so much.

The SECRET to synthesis is simple:

A) Look for patterns, as we’ll explain below. B)  when you get stuck, remember there’s likely more than one way to reach your desired product.

Coming up with a proper synthesis requires a combination of forward and reverse thinking!

We’ll cover the reverse thinking in the Retrosynthesis tutorial . For this tutorial, we’ll focus on the shorter and simpler synthesis.

Let’s start by looking for patterns.

The following questions will help you understand what to pay close attention to.

Look out for the following:

• What functional group is present on the reactant ?
• What functional group is present on the product ?
• Which reactions do I know to convert from one to the other?
• Do I know of a reaction that produces an intermediate to the above product?

“What do I have in the reactant?” A reactive pi bond!

“ What do I have in the product?” An alcohol.

“Which reaction do I know can help me convert from an alkene to an alcohol?”

Well, there are many if you think about it. Let’s go in order from most obvious to less obvious:

• Acid catalyzed hydration
• Oxymercuration-demercuration
• Hydroboration-oxidation

But what if you weren’t given the alkene, or didn’t think of these alkene reactions? What about putting a halogen leaving group on the alkene through hydrohalogenation ? Or a radical halogenation if starting with an alkane?

What if it wasn’t that easy?

What if you’re asked to start with an alkyne?

This is where we introduce many options: –> If you reduce the alkyne to an alkene, you may use one of the following as already discussed above:

–> If you go from the alkyne to a carbonyl (ketone or aldehyde) you can follow up by reduction:

Do you see where we’re going with this?

A) Identify the patterns B) Ask yourself, “What do I know?” to recognize these patterns C) Go from there

Let’s start with a simple example for concept, then apply the same logic to something more complicated.

• What functional group is present on the reactant ? Reactive terminal alkyne
• What functional group is present on the product ? Ketone on carbon #2
• Which reactions do I know to convert from one to the other? Acid catalyzed hydration of alkynes will yield a ketone following Markovnikov’s Rule .

HOWEVER ,  in this example we’re starting with a 3-carbon chain yet ending with a 4-carbon chain.

4. Do I know of a reaction that produces an intermediate to the above product? Yes! Terminal alkynes easily undergo chain elongation via SN2.

We'll start with an acid/base reaction  to deprotonate the terminal alkyne forming a good nucleophile.

But wait, the product is an enol, not a ketone!!

And there we have it!

Even scarier than a synthesis by itself is the following exam question/request:

“Propose a reasonable mechanism to carry out the following synthesis.”

This is where you’re given one reactant, one product, and ONE or TWO sets of reagents. In other words, you’re given all the steps but asked to show how the different molecules work together.

While the question is completely different, the concept is the same .

We’ll modify the initial questions slightly:

• WHERE IS THE REACTIVITY ON THE STARTING MOLECULE? As in, where do I start the mechanism?

A student recently showed me this exam question for which not a single student in his class got full credit.

Let me preface this by saying YES, this is a tough question. BUT, if you think through it logically, you’ll realize that if you studied the individual steps and recognize them, you should be able to follow along.

In fact, I challenge you to give this a try and see how far you get before reading on.

Propose a reasonable mechanism for the following reaction. show all intermediates and formal charges. is this reaction sn1 sn2 e1 e2 .

What do you think? Did you get it?

Here's a video with a step by step solution: 

No matter how well you prepare, you'll still get caught off-guard by one tricky step or another.

And when you get stuck?

Chances are, there’s more than one way to derive your product!

When I took my first weekly Organic Chemistry 2 quiz, I inadvertently set a trend of scoring top of the class, but it was a fluke. I didn’t realize we had weekly quizzes…

We were asked to outline a step by step procedure to separate two similar molecules with different functional groups. The process involved a series of reactions to prepare one molecule for extraction.

I remembered that there were about six steps, but I could only confidently answer four. I’d already bombed, then aced Orgo 1, and didn’t want to do that again!

No matter what I did, I couldn’t come up with the other steps. So instead, I crossed out my four and a half steps and wrote a detailed step by step procedure for carrying out fractional distillation.

My TA very reluctantly gave me full credit with an amused warning. No one else came close.

Am I asking you to outsmart the question?

Just recognize that the more reactions you learn, the more options you have for creating a single functional group.

If you're stuck on a certain pathway or can’t fully describe the steps, Ask yourself, “Is there another way to create the same functional group?”

Think back to the many alcohol formation reactions we discussed above. If you forgot one option, simply use another.

Here are a few interesting patterns and alternates to consider.

–> Chain Elongation ‘Go-To’ reactions

• Use alkynes in Orgo 1
• Use grignards or condensation in Orgo 2

–> Adding carboxylic acids or carbonyls

• Alcohol -> oxidation
• Oxidative cleavage using KMnO4 or O3 (smaller chain)
• Grignard and CO2 (longer chain)

–> ‘Moving’ Reactivity so that you can start/react at a different portion of the molecule compared to the current location of the active group.

Active groups include leaving groups, pi bonds, nucleophilic centers susceptible to attack and more.

• Move the Pi bond intermediate then apply a Markovnikov or Anti-Markovnikov addition .
• No pi bond? Radical halogenation to introduce a leaving group and THEN eliminate.

These are just SOME of the tricks you can utilize.

Maximizing Partial Credit On Your Exam

Gaining bonus points on exams is one thing, but here’s the best part:

The average synthesis question is worth anywhere from 10-30 points. And the average professor WILL give partial credit. So, if you can only remember four of five steps, DO NOT leave it blank to receive zero points!

Instead, write the four steps and add in as much relevant information as possible. Then VERY CONFIDENTLY fake the fifth step.

Do not write “ Magic! ”   (yes, I’ve seen this on a student exam).

Make up something that appears to be just a ‘careless’ mistake. Your professor will be impressed by your work and hopefully give you an 80% for the question.

This also applies to reagents!

If you only remember the steps, but don’t remember which reagents will get you there, start by drawing out the molecules:

A –> B –> C

This has two benefits:

• It helps you think without distractions so you can clearly see how the molecule and functional groups change/evolve from step to step.
• Now that you have a clear picture of where you’re doing, you should be able to retrace your steps and fill in the required reagents!

Of course if Reagents are giving you trouble with this, here's a video on  ‘Memorizing’ Organic Chemistry Reagents .

And if you can’t remember them, invent something rather than leave it blank.  try to use a reagent that has the groups you’re adding..

Are they correct? Not quite! Both will cleave the alkyne.

BUT, I’ve seen enough students use this as a legitimate mistake that your professor may think the same and hopefully give you partial credit.

Again, I’m not asking you to invent on your exam.

But, guessing logically on a multi-step problem where you’ve already earned sufficient points will help you get closer to full credit.

I’ve done this successfully on my orgo exams and come out top of the class, despite missing half a point here and there on multiple questions. My Study Hall members and tutoring clients do the same thing to squeeze in a few extra points, bringing them to the top.

Bottom line, make sure you learn and UNDERSTAND all of the required reactions!

But even the best of us forget some things under pressure.

That’s when you can utilize the tips above to help you try your best and you’ll have an advantage with most professors. They'll hopefully give you the benefit of the doubt when answers are questionable or not exactly what they were seeking.

Ready to start thinking backwards? That's where the more difficult topic of  Retrosynthetic Analysis or simply retrosynthesis  comes into play.

I’d love to hear from you

Do you feel better about synthesis and knowing what to do when you are stuck? Let me know in the comments below

September 26, 2018 at 12:42 pm

its too much difficult topic I can’t understand….infact i can’t thnk too much like that to propose a mechanism………Wt should I do? paper b ha?

March 1, 2018 at 8:23 am

why in this case the pi bond forms in C1 and C2 and not in C2 and C3 (more substitued alkene) https://leah4sci.com/wp-content/uploads/2016/11/Moving-Reactivity-can-help-react-a-different-portion-of-the-molecule-using-intermediates-and-then-Mark-or-Anti-Markovnikov-addition.jpg

December 23, 2017 at 1:21 pm

Great post!!This article will be extremely helpful for students. Thank you for sharing this great guide it is really well written and very easy to understand with some great tips for chemistry. Nice work!

April 23, 2017 at 12:18 pm

I can’t explain how much this just helped me for my Ochem exam this thursday! THANK YOU

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Organic Chemistry Reference Material and Cheat Sheets

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• Prof. Rick Danheiser

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• Molecular Biology
• Organic Chemistry

Learning Resource Types

Synthetic organic chemistry ii, assignments.

Problem set solutions courtesy of Wesley Austin. Used with permission.

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Home / Synthesis Problems Involving Grignard Reagents

Organometallics

By James Ashenhurst

• Synthesis Problems Involving Grignard Reagents

Last updated: July 6th, 2023 |

Grignard Practice Problems: Synthesis Exercises Involving Grignard Reagents

• Grignard reagents add once to aldehydes to give secondary alcohols and also add once  to ketones to give tertiary alcohols.
• Esters react  twice with Grignard reagents to give tertiary alcohols which contain two identical R groups.

So when working backwards in a synthesis problem involving Grignard reagents:

• Secondary alcohols can be produced two possible ways, depending on which C-C bond is formed by the Grignard reagent.
• Tertiary alcohols containing three different R groups can be produced in three possible ways, via three possible ketone precursors
• Tertiary alcohols where at least two groups are the same can be produced from an ester in only one way – the two groups that are the same will originate as Grignard reagents, and the other R group will be a part of the ester.

Table of Contents

• Solving Synthesis Problems Involving Grignard Reagents
• Three Key Reactions of Grignard Reagents
• Problem 1: Learning To Think In Reverse
• What About Esters? (And Problem 3)
• Summary: Grignard Practice Problems

Test Yourself!

1. solving synthesis problems involving grignard reagents.

Now that we’ve covered some of the most important reactions of Grignard reagents , it’s time to actually apply this knowledge to practical matters. And by practical matters, I mean synthesis. 

After all, the point of learning each of the reactions in organic chemistry is that they’re useful tools for forging and breaking certain bonds. Just like a carpenter might use a hammer, nails, screwdrivers and various saws to build a table, organic chemists apply the “tools” of organic reactions toward some kind of goal – building a molecule from simpler components, for example.

A skilled carpenter can imagine a finished table and then think backwards to what tools to use to build it from simpler parts. Similarly, organic chemists must be able to envision how a complex molecule can be made through a sequence of  reactions .

In this post, we’ll  go through three exercises that show how we can “think backwards” from the product of a Grignard reaction to its starting materials.

So let’s get started!

How do we answer a question like this?

Break it down into parts, of course! We’ll tackle A, B, and C in turn.

Here’s our plan.

First, we’ll look at what we know about Grignards in the forward direction, and then use that information to work backwards. To take a simple example, if you know that 3 + 4 = 7, then you can work backwards to figure out what number must be subtracted from 7 to give you 3.  It’s the same idea, as we’ll see.

2. Three Key Reactions of Grignard Reagents

Here’s three key reactions of Grignards we learned in a previous post : addition to aldehydes, addition to ketones, and addition to esters.

Note that in each case we’re forming C-C and breaking C-O  as well as forming O-H. In the case of the ester, the Grignard actually adds twice – a point that’s important for planning, as we’ll see.

3. Problem 1: Learning To Work “In Reverse”

Let’s look at the first molecule,  2-pentanol.

Let’s start with the obvious. It’s a secondary alcohol , as the carbon attached to OH is in turn attached to two other carbons. Looking at our list of three reactions above, we know that secondary alcohols can be made through the addition of Grignard reagents to aldehydes.

Again, note that we form C-C and O-H, and break C-O (π).

Now let’s ask: what if we were to wave a magic wand, and make this reaction act in reverse? What bonds would form and break?

We’d be  breaking  C-C and O-H, and  forming  C-O (π). Since this isn’t a “real” reaction, we use a special open-ended arrow called a “retrosynthesis arrow” to show that this is a “planned” reaction rather than an actual one.

Getting back to that earlier comment about subtraction: if you know that

and are then asked “what number must be removed from 13 to give 5 ?”

you’d just have rearrange the equation like this:

Of course, you’re very familiar with subtraction by now, but your 1st grade self probably started by thinking it was tricky. Likewise, working backwards in the context of chemical reactions is a new thing for many people. It takes practice to apply!

Getting back to 2-pentanol: as you might have noticed, there’s actually 2 ways to go about looking at this reaction in the reverse reaction, since there are  two  different C-C bonds (let’s call A and B ) that we could break to give an aldehyde and a Grignard.

• Breaking bond A (retrosynthetically) gives us butanal and methyl Grignard.
• Breaking bond B (retrosynthetically) gives us ethanal and propyl Grignard.

There’s no wrong answer here: they’re actually equally good.

After each Grignard reaction we need to do a mildly acidic workup so that we end up with the neutral alcohol. So in the forward direction we can go:

[See that I switched something around there: I made the second Grignard derived from Cl instead of Br . Whether your Grignard is Cl, Br, or I doesn’t matter – they all work fine].

4. Problem 2:

Ready for another one? Let’s look at B.

The first observation to make here is that the C attached to OH is itself attached to 3 carbons, so it’s a  tertiary alcohol. 

Going back to what we saw about the reactions of Grignards, we can suppose that this might be made through the reaction of a ketone with a Grignard reagent.

In the previous case, there were 2 different ways to make 2-pentanol. Here, there are three , because we could either break bonds A, B, or C in the “reverse” direction to give us one of 3 different combinations of ketone and Grignard reagent.

All are equally OK! Just for clarity, let’s look at each of them in the forward direction.

Again, I mixed up the halides with the Grignards here, just for variety. You might also see many different (equivalent) workup conditions for Grignard reactions.

As long as they result in protonating the intermediate alkoxide to give the alcohol, they’re fine. 

5. What About Esters? (And Problem 3)

Now you might be asking: reactions of Grignards with esters also gives tertiary alcohols. Why can’t we use this here?

The problem is that there are 3 different R groups on the tertiary alcohol . Recall that Grignards add twice to esters. Therefore, if we were to plan to use a Grignard reaction with an ester to make a tertiary alcohol, we’d need at least 2 identical R groups to be present. The bottom of the image gives some examples.

That bottom example also happens to be a good answer to question C, by the way.

C can be made through either addition of cyclohexyl Grignard to an ester, or by 2 different combinations of ketones and Grignard reagents. Can you find them? Answer below [ Note 1 ].

That’s one of the interesting things about synthesis – there are often many different ways to go about solving the same problem . In that respect, it’s also a bit like carpentry: even two different carpenters building the same table might use a slightly different sequence of events to make the same thing.

In introductory organic, we don’t get too picky about whether you pick the most efficient synthesis of a molecule. The key is just being able to get there.

6. Summary: Grignard Practice Problems

The key takeaway for this post is to  get in the habit of looking at reactions in the backwards direction as well as in the forward direction.  If you know the bonds that form and break in the forward direction, you can apply the reverse to “retrosynthetically” work backwards to its starting materials.

This is yet another reason why I harp on “what bonds form, what bonds break?” as the most important question you should ask yourself when you learn a new reaction.

In the next post we’ll look at a few more Grignard synthesis problems, but throw in a new twist – a reaction of alcohols we’ve already learned about called  oxidation. This will allow us to build up even more complex products from simpler precursors using the Grignard reaction.

Next Post: Grignard Reactions and Synthesis (2) 

Related Articles

• Grignard Reactions And Synthesis (2)
• Formation of Grignard and Organolithium Reagents
• Protecting Groups In Grignard Reactions
• Nucleophilic Acyl Substitution (With Negatively Charged Nucleophiles)
• Reactions of Grignard Reagents
• Grignard Practice Problems (MOC Membership)

Note 1.  The answer to how to make  C from the reaction of a ketone with a Grignard reagent.

00 General Chemistry Review

• Lewis Structures
• Ionic and Covalent Bonding
• Chemical Kinetics
• Chemical Equilibria
• Valence Electrons of the First Row Elements
• How Concepts Build Up In Org 1 ("The Pyramid")

01 Bonding, Structure, and Resonance

• How Do We Know Methane (CH4) Is Tetrahedral?
• Hybrid Orbitals and Hybridization
• How To Determine Hybridization: A Shortcut
• Orbital Hybridization And Bond Strengths
• Sigma bonds come in six varieties: Pi bonds come in one
• A Key Skill: How to Calculate Formal Charge
• The Four Intermolecular Forces and How They Affect Boiling Points
• 3 Trends That Affect Boiling Points
• How To Use Electronegativity To Determine Electron Density (and why NOT to trust formal charge)
• Introduction to Resonance
• How To Use Curved Arrows To Interchange Resonance Forms
• Evaluating Resonance Forms (1) - The Rule of Least Charges
• How To Find The Best Resonance Structure By Applying Electronegativity
• Evaluating Resonance Structures With Negative Charges
• Evaluating Resonance Structures With Positive Charge
• Exploring Resonance: Pi-Donation
• Exploring Resonance: Pi-acceptors
• In Summary: Evaluating Resonance Structures
• Drawing Resonance Structures: 3 Common Mistakes To Avoid
• How to apply electronegativity and resonance to understand reactivity
• Bond Hybridization Practice
• Structure and Bonding Practice Quizzes
• Resonance Structures Practice

02 Acid Base Reactions

• Introduction to Acid-Base Reactions
• Acid Base Reactions In Organic Chemistry
• The Stronger The Acid, The Weaker The Conjugate Base
• Walkthrough of Acid-Base Reactions (3) - Acidity Trends
• Five Key Factors That Influence Acidity
• Acid-Base Reactions: Introducing Ka and pKa
• How to Use a pKa Table
• The pKa Table Is Your Friend
• A Handy Rule of Thumb for Acid-Base Reactions
• Acid Base Reactions Are Fast
• pKa Values Span 60 Orders Of Magnitude
• How Protonation and Deprotonation Affect Reactivity
• Acid Base Practice Problems

03 Alkanes and Nomenclature

• Meet the (Most Important) Functional Groups
• Condensed Formulas: Deciphering What the Brackets Mean
• Hidden Hydrogens, Hidden Lone Pairs, Hidden Counterions
• Don't Be Futyl, Learn The Butyls
• Primary, Secondary, Tertiary, Quaternary In Organic Chemistry
• Branching, and Its Affect On Melting and Boiling Points
• The Many, Many Ways of Drawing Butane
• Wedge And Dash Convention For Tetrahedral Carbon
• Common Mistakes in Organic Chemistry: Pentavalent Carbon
• Table of Functional Group Priorities for Nomenclature
• Summary Sheet - Alkane Nomenclature
• Organic Chemistry IUPAC Nomenclature Demystified With A Simple Puzzle Piece Approach
• Boiling Point Quizzes
• Organic Chemistry Nomenclature Quizzes

04 Conformations and Cycloalkanes

• Staggered vs Eclipsed Conformations of Ethane
• Conformational Isomers of Propane
• Newman Projection of Butane (and Gauche Conformation)
• Introduction to Cycloalkanes
• Geometric Isomers In Small Rings: Cis And Trans Cycloalkanes
• Calculation of Ring Strain In Cycloalkanes
• Cycloalkanes - Ring Strain In Cyclopropane And Cyclobutane
• Cyclohexane Conformations
• Cyclohexane Chair Conformation: An Aerial Tour
• How To Draw The Cyclohexane Chair Conformation
• The Cyclohexane Chair Flip
• The Cyclohexane Chair Flip - Energy Diagram
• Substituted Cyclohexanes - Axial vs Equatorial
• Ranking The Bulkiness Of Substituents On Cyclohexanes: "A-Values"
• Cyclohexane Chair Conformation Stability: Which One Is Lower Energy?
• Fused Rings - Cis-Decalin and Trans-Decalin
• Naming Bicyclic Compounds - Fused, Bridged, and Spiro
• Bredt's Rule (And Summary of Cycloalkanes)
• Newman Projection Practice
• Cycloalkanes Practice Problems

05 A Primer On Organic Reactions

• The Most Important Question To Ask When Learning a New Reaction
• Learning New Reactions: How Do The Electrons Move?
• The Third Most Important Question to Ask When Learning A New Reaction
• 7 Factors that stabilize negative charge in organic chemistry
• 7 Factors That Stabilize Positive Charge in Organic Chemistry
• Nucleophiles and Electrophiles
• Curved Arrows (for reactions)
• Curved Arrows (2): Initial Tails and Final Heads
• Nucleophilicity vs. Basicity
• The Three Classes of Nucleophiles
• What Makes A Good Nucleophile?
• What makes a good leaving group?
• 3 Factors That Stabilize Carbocations
• Equilibrium and Energy Relationships
• What's a Transition State?
• Hammond's Postulate
• Learning Organic Chemistry Reactions: A Checklist (PDF)
• Introduction to Free Radical Substitution Reactions
• Introduction to Oxidative Cleavage Reactions

06 Free Radical Reactions

• Bond Dissociation Energies = Homolytic Cleavage
• Free Radical Reactions
• 3 Factors That Stabilize Free Radicals
• What Factors Destabilize Free Radicals?
• Bond Strengths And Radical Stability
• Free Radical Initiation: Why Is "Light" Or "Heat" Required?
• Initiation, Propagation, Termination
• Monochlorination Products Of Propane, Pentane, And Other Alkanes
• Selectivity In Free Radical Reactions
• Selectivity in Free Radical Reactions: Bromination vs. Chlorination
• Halogenation At Tiffany's
• Allylic Bromination
• Bonus Topic: Allylic Rearrangements
• In Summary: Free Radicals
• Synthesis (2) - Reactions of Alkanes
• Free Radicals Practice Quizzes

07 Stereochemistry and Chirality

• Types of Isomers: Constitutional Isomers, Stereoisomers, Enantiomers, and Diastereomers
• How To Draw The Enantiomer Of A Chiral Molecule
• How To Draw A Bond Rotation
• Introduction to Assigning (R) and (S): The Cahn-Ingold-Prelog Rules
• Assigning Cahn-Ingold-Prelog (CIP) Priorities (2) - The Method of Dots
• Enantiomers vs Diastereomers vs The Same? Two Methods For Solving Problems
• Assigning R/S To Newman Projections (And Converting Newman To Line Diagrams)
• How To Determine R and S Configurations On A Fischer Projection
• The Meso Trap
• Optical Rotation, Optical Activity, and Specific Rotation
• Optical Purity and Enantiomeric Excess
• What's a Racemic Mixture?
• Chiral Allenes And Chiral Axes
• Stereochemistry Practice Problems and Quizzes

08 Substitution Reactions

• Nucleophilic Substitution Reactions - Introduction
• Two Types of Nucleophilic Substitution Reactions
• The SN2 Mechanism
• Why the SN2 Reaction Is Powerful
• The SN1 Mechanism
• The Conjugate Acid Is A Better Leaving Group
• Comparing the SN1 and SN2 Reactions
• Polar Protic? Polar Aprotic? Nonpolar? All About Solvents
• Steric Hindrance is Like a Fat Goalie
• Common Blind Spot: Intramolecular Reactions
• Substitution Practice - SN1
• Substitution Practice - SN2

09 Elimination Reactions

• Elimination Reactions (1): Introduction And The Key Pattern
• Elimination Reactions (2): The Zaitsev Rule
• Elimination Reactions Are Favored By Heat
• Two Elimination Reaction Patterns
• The E1 Reaction
• The E2 Mechanism
• E1 vs E2: Comparing the E1 and E2 Reactions
• Antiperiplanar Relationships: The E2 Reaction and Cyclohexane Rings
• Bulky Bases in Elimination Reactions
• Comparing the E1 vs SN1 Reactions
• Elimination (E1) Reactions With Rearrangements
• E1cB - Elimination (Unimolecular) Conjugate Base
• Elimination (E1) Practice Problems And Solutions
• Elimination (E2) Practice Problems and Solutions

10 Rearrangements

• Introduction to Rearrangement Reactions
• Rearrangement Reactions (1) - Hydride Shifts
• Carbocation Rearrangement Reactions (2) - Alkyl Shifts
• Pinacol Rearrangement
• The SN1, E1, and Alkene Addition Reactions All Pass Through A Carbocation Intermediate

11 SN1/SN2/E1/E2 Decision

• Identifying Where Substitution and Elimination Reactions Happen
• Deciding SN1/SN2/E1/E2 (1) - The Substrate
• Deciding SN1/SN2/E1/E2 (2) - The Nucleophile/Base
• SN1 vs E1 and SN2 vs E2 : The Temperature
• Deciding SN1/SN2/E1/E2 - The Solvent
• Wrapup: The Key Factors For Determining SN1/SN2/E1/E2
• Alkyl Halide Reaction Map And Summary
• SN1 SN2 E1 E2 Practice Problems

12 Alkene Reactions

• E and Z Notation For Alkenes (+ Cis/Trans)
• Alkene Stability
• Alkene Addition Reactions: "Regioselectivity" and "Stereoselectivity" (Syn/Anti)
• Stereoselective and Stereospecific Reactions
• Hydrohalogenation of Alkenes and Markovnikov's Rule
• Hydration of Alkenes With Aqueous Acid
• Rearrangements in Alkene Addition Reactions
• Halogenation of Alkenes and Halohydrin Formation
• Oxymercuration Demercuration of Alkenes
• Hydroboration Oxidation of Alkenes
• m-CPBA (meta-chloroperoxybenzoic acid)
• OsO4 (Osmium Tetroxide) for Dihydroxylation of Alkenes
• Palladium on Carbon (Pd/C) for Catalytic Hydrogenation of Alkenes
• Cyclopropanation of Alkenes
• A Fourth Alkene Addition Pattern - Free Radical Addition
• Alkene Reactions: Ozonolysis
• Summary: Three Key Families Of Alkene Reaction Mechanisms
• Synthesis (4) - Alkene Reaction Map, Including Alkyl Halide Reactions
• Alkene Reactions Practice Problems

13 Alkyne Reactions

• Acetylides from Alkynes, And Substitution Reactions of Acetylides
• Partial Reduction of Alkynes With Lindlar's Catalyst
• Partial Reduction of Alkynes With Na/NH3 To Obtain Trans Alkenes
• Alkyne Hydroboration With "R2BH"
• Hydration and Oxymercuration of Alkynes
• Hydrohalogenation of Alkynes
• Alkyne Halogenation: Bromination, Chlorination, and Iodination of Alkynes
• Alkyne Reactions - The "Concerted" Pathway
• Alkenes To Alkynes Via Halogenation And Elimination Reactions
• Alkynes Are A Blank Canvas
• Synthesis (5) - Reactions of Alkynes
• Alkyne Reactions Practice Problems With Answers

14 Alcohols, Epoxides and Ethers

• Alcohols - Nomenclature and Properties
• Alcohols Can Act As Acids Or Bases (And Why It Matters)
• Alcohols - Acidity and Basicity
• The Williamson Ether Synthesis
• Ethers From Alkenes, Tertiary Alkyl Halides and Alkoxymercuration
• Alcohols To Ethers via Acid Catalysis
• Cleavage Of Ethers With Acid
• Epoxides - The Outlier Of The Ether Family
• Opening of Epoxides With Acid
• Epoxide Ring Opening With Base
• Making Alkyl Halides From Alcohols
• Tosylates And Mesylates
• PBr3 and SOCl2
• Elimination Reactions of Alcohols
• Elimination of Alcohols To Alkenes With POCl3
• Alcohol Oxidation: "Strong" and "Weak" Oxidants
• Demystifying The Mechanisms of Alcohol Oxidations
• Protecting Groups For Alcohols
• Thiols And Thioethers
• Calculating the oxidation state of a carbon
• Oxidation and Reduction in Organic Chemistry
• Oxidation Ladders
• SOCl2 Mechanism For Alcohols To Alkyl Halides: SN2 versus SNi
• Alcohol Reactions Roadmap (PDF)
• Alcohol Reaction Practice Problems
• Epoxide Reaction Quizzes
• Oxidation and Reduction Practice Quizzes

15 Organometallics

• What's An Organometallic?
• Organometallics Are Strong Bases
• Organocuprates (Gilman Reagents): How They're Made
• Gilman Reagents (Organocuprates): What They're Used For
• The Heck, Suzuki, and Olefin Metathesis Reactions (And Why They Don't Belong In Most Introductory Organic Chemistry Courses)
• Reaction Map: Reactions of Organometallics
• Grignard Practice Problems

16 Spectroscopy

• Degrees of Unsaturation (or IHD, Index of Hydrogen Deficiency)
• Conjugation And Color (+ How Bleach Works)
• Introduction To UV-Vis Spectroscopy
• UV-Vis Spectroscopy: Absorbance of Carbonyls
• UV-Vis Spectroscopy: Practice Questions
• Bond Vibrations, Infrared Spectroscopy, and the "Ball and Spring" Model
• Infrared Spectroscopy: A Quick Primer On Interpreting Spectra
• IR Spectroscopy: 4 Practice Problems
• 1H NMR: How Many Signals?
• Homotopic, Enantiotopic, Diastereotopic
• Diastereotopic Protons in 1H NMR Spectroscopy: Examples
• C13 NMR - How Many Signals
• Liquid Gold: Pheromones In Doe Urine
• Natural Product Isolation (1) - Extraction
• Natural Product Isolation (2) - Purification Techniques, An Overview
• Structure Determination Case Study: Deer Tarsal Gland Pheromone

17 Dienes and MO Theory

• What To Expect In Organic Chemistry 2
• Are these molecules conjugated?
• Conjugation And Resonance In Organic Chemistry
• Bonding And Antibonding Pi Orbitals
• Molecular Orbitals of The Allyl Cation, Allyl Radical, and Allyl Anion
• Pi Molecular Orbitals of Butadiene
• Reactions of Dienes: 1,2 and 1,4 Addition
• Thermodynamic and Kinetic Products
• More On 1,2 and 1,4 Additions To Dienes
• s-cis and s-trans
• The Diels-Alder Reaction
• Cyclic Dienes and Dienophiles in the Diels-Alder Reaction
• Stereochemistry of the Diels-Alder Reaction
• Exo vs Endo Products In The Diels Alder: How To Tell Them Apart
• HOMO and LUMO In the Diels Alder Reaction
• Why Are Endo vs Exo Products Favored in the Diels-Alder Reaction?
• Diels-Alder Reaction: Kinetic and Thermodynamic Control
• The Retro Diels-Alder Reaction
• The Intramolecular Diels Alder Reaction
• Regiochemistry In The Diels-Alder Reaction
• The Cope and Claisen Rearrangements
• Electrocyclic Reactions
• Electrocyclic Ring Opening And Closure (2) - Six (or Eight) Pi Electrons
• Diels Alder Practice Problems
• Molecular Orbital Theory Practice

18 Aromaticity

• Introduction To Aromaticity
• Rules For Aromaticity
• Huckel's Rule: What Does 4n+2 Mean?
• Aromatic, Non-Aromatic, or Antiaromatic? Some Practice Problems
• Antiaromatic Compounds and Antiaromaticity
• The Pi Molecular Orbitals of Benzene
• The Pi Molecular Orbitals of Cyclobutadiene
• Frost Circles
• Aromaticity Practice Quizzes

19 Reactions of Aromatic Molecules

• Electrophilic Aromatic Substitution: Introduction
• Activating and Deactivating Groups In Electrophilic Aromatic Substitution
• Electrophilic Aromatic Substitution - The Mechanism
• Ortho-, Para- and Meta- Directors in Electrophilic Aromatic Substitution
• Understanding Ortho, Para, and Meta Directors
• Why are halogens ortho- para- directors?
• Disubstituted Benzenes: The Strongest Electron-Donor "Wins"
• Electrophilic Aromatic Substitutions (1) - Halogenation of Benzene
• Electrophilic Aromatic Substitutions (2) - Nitration and Sulfonation
• EAS Reactions (3) - Friedel-Crafts Acylation and Friedel-Crafts Alkylation
• Intramolecular Friedel-Crafts Reactions
• Nucleophilic Aromatic Substitution (NAS)
• Nucleophilic Aromatic Substitution (2) - The Benzyne Mechanism
• Reactions on the "Benzylic" Carbon: Bromination And Oxidation
• The Wolff-Kishner, Clemmensen, And Other Carbonyl Reductions
• More Reactions on the Aromatic Sidechain: Reduction of Nitro Groups and the Baeyer Villiger
• Aromatic Synthesis (1) - "Order Of Operations"
• Synthesis of Benzene Derivatives (2) - Polarity Reversal
• Aromatic Synthesis (3) - Sulfonyl Blocking Groups
• Birch Reduction
• Synthesis (7): Reaction Map of Benzene and Related Aromatic Compounds
• Aromatic Reactions and Synthesis Practice
• Electrophilic Aromatic Substitution Practice Problems

20 Aldehydes and Ketones

• What's The Alpha Carbon In Carbonyl Compounds?
• Nucleophilic Addition To Carbonyls
• Aldehydes and Ketones: 14 Reactions With The Same Mechanism
• Sodium Borohydride (NaBH4) Reduction of Aldehydes and Ketones
• Grignard Reagents For Addition To Aldehydes and Ketones
• Wittig Reaction
• Hydrates, Hemiacetals, and Acetals
• Imines - Properties, Formation, Reactions, and Mechanisms
• All About Enamines
• Breaking Down Carbonyl Reaction Mechanisms: Reactions of Anionic Nucleophiles (Part 2)
• Aldehydes Ketones Reaction Practice

21 Carboxylic Acid Derivatives

• Addition-Elimination Mechanisms With Neutral Nucleophiles (Including Acid Catalysis)
• Basic Hydrolysis of Esters - Saponification
• Transesterification
• Proton Transfer
• Fischer Esterification - Carboxylic Acid to Ester Under Acidic Conditions
• Lithium Aluminum Hydride (LiAlH4) For Reduction of Carboxylic Acid Derivatives
• LiAlH[Ot-Bu]3 For The Reduction of Acid Halides To Aldehydes
• Di-isobutyl Aluminum Hydride (DIBAL) For The Partial Reduction of Esters and Nitriles
• Amide Hydrolysis
• Thionyl Chloride (SOCl2)
• Diazomethane (CH2N2)
• Carbonyl Chemistry: Learn Six Mechanisms For the Price Of One
• Making Music With Mechanisms (PADPED)
• Carboxylic Acid Derivatives Practice Questions

22 Enols and Enolates

• Keto-Enol Tautomerism
• Enolates - Formation, Stability, and Simple Reactions
• Kinetic Versus Thermodynamic Enolates
• Aldol Addition and Condensation Reactions
• Reactions of Enols - Acid-Catalyzed Aldol, Halogenation, and Mannich Reactions
• Claisen Condensation and Dieckmann Condensation
• Decarboxylation
• The Malonic Ester and Acetoacetic Ester Synthesis
• The Michael Addition Reaction and Conjugate Addition
• The Robinson Annulation
• Haloform Reaction
• The Hell–Volhard–Zelinsky Reaction
• Enols and Enolates Practice Quizzes
• The Amide Functional Group: Properties, Synthesis, and Nomenclature
• Basicity of Amines And pKaH
• 5 Key Basicity Trends of Amines
• The Mesomeric Effect And Aromatic Amines
• Nucleophilicity of Amines
• Alkylation of Amines (Sucks!)
• Reductive Amination
• The Gabriel Synthesis
• Some Reactions of Azides
• The Hofmann Elimination
• The Hofmann and Curtius Rearrangements
• The Cope Elimination
• Protecting Groups for Amines - Carbamates
• The Strecker Synthesis of Amino Acids
• Introduction to Peptide Synthesis
• Reactions of Diazonium Salts: Sandmeyer and Related Reactions
• Amine Practice Questions

24 Carbohydrates

• D and L Notation For Sugars
• Pyranoses and Furanoses: Ring-Chain Tautomerism In Sugars
• What is Mutarotation?
• Reducing Sugars
• The Big Damn Post Of Carbohydrate-Related Chemistry Definitions
• The Haworth Projection
• Converting a Fischer Projection To A Haworth (And Vice Versa)
• Reactions of Sugars: Glycosylation and Protection
• The Ruff Degradation and Kiliani-Fischer Synthesis
• Isoelectric Points of Amino Acids (and How To Calculate Them)
• Carbohydrates Practice
• Amino Acid Quizzes

25 Fun and Miscellaneous

• A Gallery of Some Interesting Molecules From Nature
• Screw Organic Chemistry, I'm Just Going To Write About Cats
• On Cats, Part 1: Conformations and Configurations
• On Cats, Part 2: Cat Line Diagrams
• On Cats, Part 4: Enantiocats
• On Cats, Part 6: Stereocenters
• Organic Chemistry Is Shit
• The Organic Chemistry Behind "The Pill"
• Maybe they should call them, "Formal Wins" ?
• Why Do Organic Chemists Use Kilocalories?
• The Principle of Least Effort
• Organic Chemistry GIFS - Resonance Forms
• Reproducibility In Organic Chemistry
• What Holds The Nucleus Together?
• How Reactions Are Like Music
• Organic Chemistry and the New MCAT

26 Organic Chemistry Tips and Tricks

• Common Mistakes: Formal Charges Can Mislead
• Partial Charges Give Clues About Electron Flow
• Draw The Ugly Version First
• Organic Chemistry Study Tips: Learn the Trends
• The 8 Types of Arrows In Organic Chemistry, Explained
• Top 10 Skills To Master Before An Organic Chemistry 2 Final
• Common Mistakes with Carbonyls: Carboxylic Acids... Are Acids!
• Planning Organic Synthesis With "Reaction Maps"
• Alkene Addition Pattern #1: The "Carbocation Pathway"
• Alkene Addition Pattern #2: The "Three-Membered Ring" Pathway
• Alkene Addition Pattern #3: The "Concerted" Pathway
• Number Your Carbons!
• The 4 Major Classes of Reactions in Org 1
• How (and why) electrons flow
• Grossman's Rule
• Three Exam Tips
• A 3-Step Method For Thinking Through Synthesis Problems
• Putting It Together
• Putting Diels-Alder Products in Perspective
• The Ups and Downs of Cyclohexanes
• The Most Annoying Exceptions in Org 1 (Part 1)
• The Most Annoying Exceptions in Org 1 (Part 2)
• The Marriage May Be Bad, But the Divorce Still Costs Money
• 9 Nomenclature Conventions To Know
• Nucleophile attacks Electrophile

27 Case Studies of Successful O-Chem Students

• Success Stories: How Corina Got The The "Hard" Professor - And Got An A+ Anyway
• How Helena Aced Organic Chemistry
• From a "Drop" To B+ in Org 2 – How A Hard Working Student Turned It Around
• How Serge Aced Organic Chemistry
• Success Stories: How Zach Aced Organic Chemistry 1
• Success Stories: How Kari Went From C– to B+
• How Esther Bounced Back From a "C" To Get A's In Organic Chemistry 1 And 2
• How Tyrell Got The Highest Grade In Her Organic Chemistry Course
• This Is Why Students Use Flashcards
• Success Stories: How Stu Aced Organic Chemistry
• How John Pulled Up His Organic Chemistry Exam Grades
• Success Stories: How Nathan Aced Organic Chemistry (Without It Taking Over His Life)
• How Chris Aced Org 1 and Org 2
• Interview: How Jay Got an A+ In Organic Chemistry
• How to Do Well in Organic Chemistry: One Student's Advice
• "America's Top TA" Shares His Secrets For Teaching O-Chem
• "Organic Chemistry Is Like..." - A Few Metaphors
• How To Do Well In Organic Chemistry: Advice From A Tutor
• Guest post: "I went from being afraid of tests to actually looking forward to them".

Comment section

14 thoughts on “ synthesis problems involving grignard reagents ”.

Thanks alot you really help me but my question is having a skeletal structure like this one

/+\/\// having a carbonation how can one predict the nucleophile,electrophile and curved arrows to show the attack of the nucleophile on the electrophile

I think you’re describing a reaction where the alkene acts as a nucleophile on the carbocation electrophile, forming a cyclic five-membered ring with a new carbocation. There’s some examples in this article (go to the bottom) – https://www.masterorganicchemistry.com/2013/02/08/markovnikovs-rule-1/

hello sir. in case of esters when the RO- group leaves, a carbocation is formed and thereafter oxygen donates it’s LP and we get a ketone. My question is if carbocation rearrangement will be possible?

No carbocation is formed. The new C-O pi bond forms at the same time as the C-O single bond breaks. This mechanism is known as “elimination” or sometimes 1,2-elimination.

No carbocation rearrangement occurs because there is no carbocation.

Is -NHBoc compatible with grignard reagent? I am trying to make a grignard reagent bearing -NHBoc but turned unsuccessful. And I didn’t find similar examples from reaxys.

No, proton is too acidic for a Grignard. Will just deprotonate

thank you so much for this, cheers!

Glad you find it helpful Lynn.

Wow Really helpful especially in the retro synthesis products

Thank you for that helpful post

Sir you are literally my Ogchem saver🙏

This is great and a big help. Thank you!

Glad to hear it Daniel!

Thank you so much! This is extremely helpful!

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