Work backward through known transformations, execute forward through exact intermediate states, and carry every scaffold atom, reactive site, workup, and selectivity boundary to the target.
Write the target atom, bond, functional-group, regioselective, and stereochemical deltas.
02Disconnect
Choose a simpler precursor connected by a known forward reaction with known limits.
03Execute
Reverse the analysis and list every reagent, intermediate, spectator group, and workup.
04Verify
Close the atom, compatibility, protection, stereochemical, and route-comparison ledgers.
The four official topic lines come from the ADA Organic Chemistry specification ↗. The route-ledger method and original cases are DAT TRAIN study tools, not ADA weights.
Four connected synthesis lessons
The route is only as strong as its weakest handoff.
Each lesson pairs a planning rule with a complete route ledger. Scaffold counts follow target-bearing heavy atoms; temporary protecting-group atoms are called out and excluded.
01
LESSON 1 · 25 MIN
Two-step routes
Make the intermediate earn its place
Plan, order, and verify two-step routes from target requirements, continuous intermediate states, and scaffold-atom provenance.
ESSENTIAL QUESTIONWhat exact intermediate can be made from the start and consumed to make the target?
R01
Install one carbon through a nitrile
1-bromopropane → butanoic acid
001-bromopropanealkyl-halide · C3 · Br1
01butanenitrilenitrile · C4 · N1
02butanoic acidcarboxylic-acid · C4 · O2
Complete route ledger for Install one carbon through a nitrile
Step
Input → output
Conditions + workup
Group ledger
Selectivity boundary
1 · SN2 cyanide substitution
1-bromopropane → butanenitrile
NaCN; no separate workup
Target: alkyl-halide; preserve: none
The declared target group changes while every listed spectator group is preserved. This ledger validates the named transformation and stated conditions; it does not predict an experimental yield unless one is supplied.
2 · nitrile hydrolysis
butanenitrile → butanoic acid
H3O+; heat; workup: aqueous acid
Target: nitrile; preserve: none
The declared target group changes while every listed spectator group is preserved. This ledger validates the named transformation and stated conditions; it does not predict an experimental yield unless one is supplied.
ACCESSIBLE ROUTE MODEL · COMPLETE STATE, CONDITION, GROUP, AND BOUNDARY TABLE INCLUDED
01
Work backward one transformation
Name a plausible immediate precursor whose conversion supplies the target functional group and required carbon skeleton.
Target to precursor
State the bond or group change
02
Reconnect to the start
The first operation must produce the same intermediate the second operation consumes under compatible conditions.
Exact handoff
Order follows required input
03
Audit the complete route
Balance scaffold atoms, declare workups, and verify that the final state—not just a familiar reaction name—matches the target.
Track carbon sources
Include required workup
Worked example
Plan butanoic acid from 1-bromopropane.
1
Work backward from the acid to a nitrile that can hydrolyze.
2
Make butanenitrile by SN2 substitution of the primary bromide with cyanide.
3
Count the cyanide carbon and then hydrolyze the nitrile through the stated aqueous workup.
ConclusionThe nitrile is a productive intermediate because it connects both transformations and explains the one-carbon increase.
Close the notes first
Retrieve the route rule.
01What makes an intermediate valid?
It must be the actual output of one step and required input of the next.
A name-only sequence can hide a broken handoff.
02Where does the extra carbon in alkyl halide → nitrile come from?
The carbon of cyanide.
Cyanide becomes part of the target scaffold.
03Why is a workup part of the route?
It creates or isolates the declared product state after the reactive step.
Omitting it can leave the wrong protonation or reagent-bound state.
02
LESSON 2 · 28 MIN
Multistep routes
Plan backward; execute forward
Choose productive disconnections, translate them into a coherent forward sequence, and compare viable routes with explicit constraints.
ESSENTIAL QUESTIONWhich disconnection simplifies the target without creating an impossible forward step?
R08
Reject the attractive shortcut
2-bromopropane → 2-methyl-2-propanol
002-bromopropanealkyl-halide · C3 · Br1
01propenealkene · C3
022-propanolfree-alcohol · C3 · O1
03acetoneketone · C3 · O1
042-methyl-2-propanolfree-alcohol · C4 · O1
Complete route ledger for Reject the attractive shortcut
Step
Input → output
Conditions + workup
Group ledger
Selectivity boundary
1 · E2 dehydrohalogenation
2-bromopropane → propene
KOEt; ethanol; heat; no separate workup
Target: alkyl-halide; preserve: none
The declared target group changes while every listed spectator group is preserved. This ledger validates the named transformation and stated conditions; it does not predict an experimental yield unless one is supplied.
2 · Markovnikov hydration
propene → 2-propanol
H2O; H2SO4; no separate workup
Target: alkene; preserve: none
The declared target group changes while every listed spectator group is preserved. This ledger validates the named transformation and stated conditions; it does not predict an experimental yield unless one is supplied.
3 · secondary alcohol oxidation
2-propanol → acetone
PCC; workup: filtration
Target: free-alcohol; preserve: none
The declared target group changes while every listed spectator group is preserved. This ledger validates the named transformation and stated conditions; it does not predict an experimental yield unless one is supplied.
4 · Grignard addition
acetone → 2-methyl-2-propanol
1. CH3MgBr; 2. H3O+; workup: aqueous acid after carbon–carbon bond formation
Target: ketone; preserve: none
The declared target group changes while every listed spectator group is preserved. This ledger validates the named transformation and stated conditions; it does not predict an experimental yield unless one is supplied.
Supplied route comparison
Four selective operationseligible
One extra operation, but all groups and workups are compatible.
Three-step lower-yield routeeligible
Fewer steps but lower overall material throughput.
Two-step incompatible shortcutrejected
The proposed organometallic reagent is quenched before the required bond formation.
ACCESSIBLE ROUTE MODEL · COMPLETE STATE, CONDITION, GROUP, AND BOUNDARY TABLE INCLUDED
01
Choose a productive disconnection
Work backward through a known transformation whose limits, stereochemical outcome, and substrate requirements are understood.
Known forward reaction
Simpler immediate precursor
02
Reverse the analysis
Retrosynthetic arrows propose precursors; the written synthesis must reverse them into a forward sequence with every reagent and workup.
Backward plan
Forward execution
03
Compare after gating
Reject incompatible or nonselective routes before comparing overall yield, step count, or supplied practical constraints.
Feasibility first
Multiply step yields
Worked example
Plan cis-2-hexene from 1-pentyne.
1
Identify 2-hexyne as the immediate precursor that can set cis geometry by partial hydrogenation.
2
Disconnect one methyl group to recover the terminal 1-pentyne acetylide precursor.
3
Run acetylide methylation first and Lindlar reduction last.
ConclusionThe final stereochemistry-setting step stays last, while the carbon–carbon bond is built on the alkyne precursor.
Close the notes first
Retrieve the route rule.
01What does a retrosynthetic arrow mean?
A proposed precursor relationship, not a forward reagent step.
The actual synthesis must be written in the reverse order.
02How is overall route yield calculated?
Multiply the fractional yield of every step.
Material loss compounds across the sequence.
03Can a shorter incompatible route win?
No.
Compatibility and selectivity are feasibility gates.
03
LESSON 3 · 29 MIN
Functional-group selectivity
Inventory every reactive site
Predict competing reactivity, select conditions that preserve spectator groups, and use a complete protection cycle only when necessary.
ESSENTIAL QUESTIONWhat else in the molecule can react under the proposed conditions?
The declared target group changes while every listed spectator group is preserved. Protecting-group atoms are temporary and excluded from the target-scaffold atom ledger.
The declared target group changes while every listed spectator group is preserved. This ledger validates the named transformation and stated conditions; it does not predict an experimental yield unless one is supplied.
The declared target group changes while every listed spectator group is preserved. This ledger validates the named transformation and stated conditions; it does not predict an experimental yield unless one is supplied.
The declared target group changes while every listed spectator group is preserved. This ledger validates the named transformation and stated conditions; it does not predict an experimental yield unless one is supplied.
ACCESSIBLE ROUTE MODEL · COMPLETE STATE, CONDITION, GROUP, AND BOUNDARY TABLE INCLUDED
01
List targets and spectators
Carry every functional group through each state instead of drawing only the group intended to change.
Target group
Preserved groups
02
Check condition conflicts
A free alcohol quenches Grignard reagents, strong hydrides can reduce esters, and a nitro group can block Friedel–Crafts chemistry.
Acid–base compatibility
Chemoselective reagent strength
03
Close temporary cycles
If protection is needed, record protection, compatible transformation, and deprotection before declaring the target reached.
Protect before conflict
Deprotect before target
Worked example
Carboxylate 3-bromopropan-1-ol through a Grignard reagent.
1
Recognize that the free alcohol would quench the organomagnesium reagent.
2
Protect the alcohol, form the Grignard reagent in dry ether, then capture carbon dioxide before aqueous acid.
3
Remove the silyl protecting group and confirm the hydroxy-acid target and one-carbon increase.
ConclusionProtection solves a named incompatibility and is complete only after deprotection restores the target alcohol.
Close the notes first
Retrieve the route rule.
01Why protect a free alcohol before Grignard formation?
Its acidic proton would quench the organomagnesium reagent.
The acid–base reaction would consume the intended nucleophile.
02What must happen to every spectator group?
It must be explicitly preserved, deliberately transformed, or protected.
Untracked groups can invalidate selectivity.
03When is a protection cycle complete?
When the group is protected before conflict and restored before the final target.
A protected intermediate is not the requested unprotected target.
04
LESSON 4 · 27 MIN
Route audit
Audit the route, not the resemblance
Translate targets into requirements, recall reactions by function and boundary, and perform a complete feasibility audit.
ESSENTIAL QUESTIONDoes every state, atom source, condition, workup, and selectivity claim support the same route?
Complete route ledger for Install the viable director first
Step
Input → output
Conditions + workup
Group ledger
Selectivity boundary
1 · Friedel–Crafts acylation
benzene → acetophenone
CH3COCl; AlCl3; workup: aqueous workup
Target: arene; preserve: arene
The declared target group changes while every listed spectator group is preserved. This ledger validates the named transformation and stated conditions; it does not predict an experimental yield unless one is supplied.
2 · aromatic nitration
acetophenone → m-nitroacetophenone
HNO3; H2SO4; workup: aqueous isolation
Target: arene; preserve: arene, ketone
The acyl substituent directs nitration meta in this bounded route. This ledger validates the named transformation and stated conditions; it does not predict an experimental yield unless one is supplied.
Supplied route comparison
Acylate, then nitrateeligible
The deactivating acyl group slows but directs the second substitution meta.
Nitrate, then attempt acylationrejected
A nitro group strongly deactivates the ring, so the later Friedel–Crafts acylation is not viable.
ACCESSIBLE ROUTE MODEL · COMPLETE STATE, CONDITION, GROUP, AND BOUNDARY TABLE INCLUDED
01
Write requirements before reagents
Record carbon change, bond change, functional-group change, and stereochemical requirement before searching memory for a reaction.
Target delta
Needed reaction function
02
Recall function with boundary
Store transformations as input → output functions tied to regiochemical, stereochemical, substrate, and workup limits.
Function, not incantation
Limits travel with reagents
03
Run the final audit
Check continuity, atoms, competing sites, workups, protection balance, and route comparison without overclaiming experimental performance.
Every ledger closes
Study feasibility is not lab safety
Worked example
Compare the supplied selective, lower-yield, and incompatible routes.
1
Reject the shortcut because its conditions cannot execute the required bond formation.
2
Multiply each eligible route's fractional step yields rather than averaging them.
3
Select 81.45% over 57.38%, then state that the supplied comparison omits unmodeled cost and safety factors.
ConclusionA longer route can be preferred when it is feasible, selective, and higher yielding overall.
Close the notes first
Retrieve the route rule.
01What should be written before a reagent list?
The target's atom, bond, functional-group, and stereochemical requirements.
Requirements constrain which reactions can actually solve the problem.
02What travels with a reaction function?
Its substrate, regioselectivity, stereoselectivity, compatibility, and workup boundaries.
Reagent recall without limits creates invalid sequences.
03What does a study-level route audit not establish?
Laboratory safety or measured yield beyond supplied data.
Those claims require experimental and procedural evidence.
Randomized synthesis retrieval
Choose the route that closes.
All sixteen route cases are represented. Questions and five-choice answer sets shuffle without detaching the validated intermediate, atom source, condition, or boundary.
16 PRACTICE QUESTIONS
Retrieve before you review.
Question order and all five answer options are shuffled when you begin. The correct answer stays attached to the same underlying choice.
Scope and score notice
A viable study route is not a laboratory procedure.
This route covers all four remaining Chemical Synthesis topic lines and every frozen synthesis objective. The ADA does not publish line-level quotas, so DAT TRAIN does not invent them.
The validators enforce route continuity, scaffold accounting, compatibility, workups, selectivity, protection balance, and supplied yield comparison. They do not establish safety, measured yield, official difficulty, or completion-form calibration.