Csir net organic synthesis revision notes and mindmaps

CSIR-NET Organic Synthesis – Deep Revision Notes with Tricks & Mind Maps

(Disconnection | Synthons | Protecting Groups | Linear vs. Convergent Synthesis)

1. Disconnection (Retrosynthetic Analysis)

Definition

A logical backward-thinking process where the target molecule (TM) is progressively simplified into readily available or known starting materials.

Core Principle

Always think in terms of functional group interconversion (FGI) + strategic C–C or C–heteroatom bond cleavage.

Key Steps in Disconnection

Identify the target functional group (FG).
Perform FGI if needed (convert to a related FG easier to disconnect).
Choose disconnection points that:

Generate stable synthons.
Correspond to known synthetic reactions.
Minimize steps in forward synthesis.

Check symmetry — symmetrical molecules often have simpler disconnections.
Validate synthetic feasibility in the forward direction.

Shortcut Framework – F.A.D.E.S.

Functional group first → Handle FG interconversion before bond breaking.
Avoid unstable intermediates (e.g., tertiary carbocations in absence of rearrangements).
Disconnect strategic bonds — those formed in robust, high-yield reactions.
Exploit symmetry to reduce complexity.
Select the shortest synthetic path.

CSIR Common Disconnection Patterns

α–C to carbonyl disconnection → Aldol, Claisen, Michael additions.
Alcohol disconnection → Grignard addition to aldehyde/ketone.
Ether disconnection → Williamson synthesis (RO⁻ + R–X).
Amide/ester disconnection → Acid derivative + amine/alcohol.
Aromatic substitution disconnection → Electrophilic aromatic substitution precursors.

Exam Trap Alert 🎯

Don’t choose a disconnection just because it’s easy — it must be practical in the lab with reagents that exist and conditions that work.
Avoid “fancy” disconnections that require unisolable or unstable species unless the question specifically points toward them.

2. Synthons

Definition

An idealized fragment (nucleophilic or electrophilic) obtained after retrosynthetic cleavage, representing how a molecule could be made from simple building blocks.

Types of Synthons

Nucleophilic synthons (Nu) – electron-rich, attack electrophiles.
Example: –CN⁻, –CH₂⁻, –OH⁻
Electrophilic synthons (E) – electron-deficient, attacked by nucleophiles.
Example: CH₃⁺, acylium ion, carbonyl C=O.

Real Reagent Mapping (Synthetic Equivalents)

–CH₂⁻ → Malonic ester, Wittig ylides, CH₂I₂ + Zn–Cu (Simmons–Smith).
CH₃⁺ → CH₃I, CH₃OTs.
–CN → NaCN, KCN.
Acyl cation → Acid chloride (R–COCl).

Shortcut Method – S.N.A.P.

See functional group & polarity.
Note nucleophile/electrophile assignment.
Assign stable lab equivalents.
Pair them in forward synthesis to check feasibility.

Memory Image

Picture synthons as puzzle pieces: one has a bump (Nu), one has a hole (E). Only matching shapes fit.

Mind Map – Synthons

3. Protecting Groups (PGs)

Purpose

Temporarily mask reactive sites to prevent unwanted reactions during multi-step synthesis.

Ideal PG Characteristics

Easy to install & remove.
Stable under reaction conditions of other steps.
Selective for one functional group.

Common PGs in CSIR Context

For Alcohols

TBDMS (tert-butyldimethylsilyl) → Installed with TBDMS-Cl, removed with TBAF.
Acetyl group → Installed with Ac₂O/pyridine, removed with NaOH/H₂O.

For Carbonyls

Acetal/Ketal → HO–CH₂–CH₂–OH, acid catalysis; removed by acid hydrolysis.
1,3-dioxolane/dioxane rings for aldehydes/ketones.

For Amines

Boc (tert-butoxycarbonyl) → Installed with Boc₂O, removed with HCl in dioxane.
Cbz (carbobenzyloxy) → Installed with Cbz-Cl, removed by hydrogenolysis (H₂/Pd).

Shortcut Rule – “Acid Loves Acetal”

Formed in acid, removed in acid.
Therefore: If acid steps are ahead → choose base-labile PG; if base steps ahead → choose acid-labile PG.

Mind Map – Protecting Groups

   Protecting Groups
        |
---------------------
|        |          |
OH PG    C=O PG     NH2 PG

4. Linear vs. Convergent Synthesis

Linear Synthesis

Steps occur sequentially.
Overall yield drops drastically with number of steps.
Good for simple targets.

Convergent Synthesis

Build large fragments separately, then couple.
Higher overall yield for complex targets.
Often used in natural product synthesis.

Yield Rule Example (90% per step)

Linear (5 steps) → 0.9⁵ = 59% yield.
Convergent (two 3-step fragments + coupling) → 0.9³ × 0.9³ × 0.9 = 66% yield.

Topic	Trick / Shortcut
Disconnection	Always start from FG → FGI → bond break
Synthons	Assign polarity → replace with real reagent
Protecting Groups	Choose PG opposite to upcoming condition (acid/base)
Linear Synthesis	Count steps → estimate % yield loss
Convergent	Build fragments in parallel for higher yield