Putting it together (1)
- “Initial Tails” and “Final Heads”
- 3 Ways To Make OH A Better Leaving Group
- A Simple Formula For 7 Important Aldehyde/Ketone Reactions
- Acetoacetic
- Acids (Again!)
- Activating and Deactivating
- Actors In Every Acid Base Reaction
- Addition – Elimination
- Addition Pattern 1 – Carbocations
- Addition pattern 2 – 3 membered rings
- Addition Reactions
- Aldehydes And Ketones – Addition
- Alkene Pattern #3 – The “Concerted” Pathway
- Alkyl Rearrangements
- Alkynes – 3 Patterns
- Alkynes: Deprotonation and SN2
- Amines
- Aromaticity: Lone Pairs
- Avoid These Resonance Mistakes
- Best Way To Form Amines
- Bulky Bases
- Carbocation Stability
- Carbocation Stability Revisited
- Carboxylic Acids are Acids
- Chair Flips
- Cis and Trans
- Conformations
- Conjugate Addition
- Curved Arrow Refresher
- Curved Arrows
- Decarboxylation
- Determining Aromaticity
- Diels Alder Reaction – 1
- Dipoles: Polar vs. Covalent Bonding
- E2 Reactions
- Electronegativity Is Greed For Electrons
- Electrophilic Aromatic Substitution – Directing Groups
- Elimination Reactions
- Enantiocats and Diastereocats
- Enolates
- Epoxides – Basic and Acidic
- Evaluating Resonance Forms
- Figuring Out The Fischer
- Find That Which Is Hidden
- Formal Charge
- Frost Circles
- Gabriel Synthesis
- Grignards
- Hofmann Elimination
- How Acidity and Basicity Are Related
- How Are These Molecules Related?
- How Stereochemistry matters
- How To Stabilize Negative Charge
- How To Tell Enantiomers From Diastereomers
- Hybridization
- Hybridization Shortcut
- Hydroboration
- Imines and Enamines
- Importance of Stereochemistry
- Intermolecular Forces
- Intro to Resonance
- Ketones on Acid
- Kinetic Thermodynamic
- Making Alcohols Into Good Leaving Groups
- Markovnikov’s rule
- Mechanisms Like Chords
- Mish Mashamine
- More On The E2
- Newman Projections
- Nucleophiles & Electrophiles
- Nucleophilic Aromatic Substitution
- Nucleophilic Aromatic Substitution 2
- Order of Operations!
- Oxidation And Reduction
- Oxidative Cleavage
- Paped
- Pi Donation
- Pointers on Free Radical Reactions
- Protecting Groups
- Protecting Groups
- Proton Transfer
- Putting it together (1)
- Putting it together (2)
- Putting it together (3)
- Putting the Newman into ACTION
- Reaction Maps
- Rearrangements
- Recognizing Endo and Exo
- Redraw / Modify
- Robinson Annulation
- Robinson Annulation Mech
- Sigma and Pi Bonding
- SN1 vs SN2
- sn1/sn2 – Putting It Together
- sn1/sn2/e1/e2 – Exceptions
- sn1/sn2/e1/e2 – Nucleophile
- sn1/sn2/e1/e2 – Solvent
- sn1/sn2/e1/e2 – Substrate
- sn1/sn2/e1/e2 – Temperature
- Stereochemistry
- Strong Acid Strong Base
- Strong And Weak Oxidants
- Strong and Weak Reductants
- Stronger Donor Wins
- Substitution
- Sugars (2)
- Synthesis (1) – “What’s Different?”
- Synthesis (2) – What Reactions?
- Synthesis (3) – Figuring Out The Order
- Synthesis Part 1
- Synthesis Study Buddy
- Synthesis: Walkthrough of A Sample Problem
- Synthesis: Working Backwards
- t-butyl
- Tautomerism
- The 4 Actors In Every Acid-Base Reaction
- The Claisen Condensation
- The E1 Reaction
- The Inflection Point
- The Meso Trap
- The Michael Reaction
- The Nucleophile Adds Twice (to the ester)
- The One-Sentence Summary Of Chemistry
- The Second Most Important Carbonyl Mechanism
- The Single Swap Rule
- The SN1 Reaction
- The SN2 Reaction
- The Wittig Reaction
- Three Exam Tips
- Tips On Building Molecular Orbitals
- Top 10 Skills
- Try The Acid-Base Reaction First
- Two Key Reactions of Enolates
- What makes a good leaving group?
- What Makes A Good Nucleophile?
- What to expect in Org 2
- Work Backwards
- Zaitsev’s Rule
I have a lot of students ask me about how to do synthesis. Today, I’ll share with you a 3-step method I suggest to them, and today we’ll start to go through it. It goes like this:
- Analyze the starting material and the product – ask yourself, what bonds are formed and what bonds are broken?
- When you’ve made your list, ask yourself – what reactions do I know that will form/break these bonds?
- In what order do I do these reactions?
As an illustration, let’s use this synthesis question for alkynes.
Part 1. Asking “what’s new” ?
A lot of students expect that they’ll be able to look at a synthesis problem and “just see the answer”. This is not how it works. A synthesis question is a bit like solving a Sudoku . There’s a method to it. Before you can make headway, you have to do some arithmetic first.
Step 1 is where you do your arithmetic. It might really help if you draw out all the hidden hydrogens, because these can be hard to spot. You want to make as complete a list of the bonds that form and break as possible – including all the hydrogens.
Like this:
Part 2: Asking “what are some potential reactions?”
The next step is to ask yourself what reactions form and break these bonds. There’s no getting around the fact that you have to know what each reaction does. But there are a few general hints (that extend beyond alkynes):
- any time you’re breaking a C-C (pi) bond, it’s an addition reaction
- if you’re forming a C-C (pi) bond, it’s an elimination reaction.
- substitution reactions form and break a bond on the same carbon
- look for good leaving groups
- pay close attention to stereochemistry
For the reaction we’re talking about, we’re breaking two C-C (pi) bonds, which points to two addition reactions. We’re forming two C-H bonds and two C-OH bonds.
What are some addition reactions that will form these bonds? Here, you have to come up with a list of possibilities. We’re just “playing around” here.
- Hydroboration (form C-H, form C-OH)
- Hydration (form C-H, form C-OH)
- dihydroxylation (form C-OH, form C-OH)
- hydrogenation (form C-H, form C-H)
Tomorrow, we’ll go through these possibilities and figure out which ones make sense and which don’t.
Thanks for reading! James