C5R CORP.

Maximize amide synthesis yield

Physical end-to-end experiments
Task space

Maximize the yield of N-benzyl-4-methylbenzamide from p-toluic acid and benzylamine in a rapid amide-forming reaction.

Conditions that produce high yields quickly can accelerate experimental iteration and increase laboratory throughput. Here, the short reaction window challenges agents to find conditions that form substantial product within a fixed time budget.

Agents have less than three minutes from amine addition to completed quenching. They select reagents and conditions, execute the reaction, and measure yield by LC–MS using a pre-recorded calibration curve. The task tests reaction optimization alongside precise timing, quenching, and sample preparation.

Scoring

The calibrated amide yield must reach at least the human baseline (6.13%) within the three-minute reaction limit. An attempt that exceeds the time limit fails.

RESULTS

Maximize the yield of N-benzyl-4-methylbenzamide from p-toluic acid and benzylamine in a rapid amide-forming reaction.
ModelPass@1Cost ($)Model/API inference cost only, averaged per task attempt. Lab and labor costs are not reported. Repeats are averaged using the same task and family weights as scores.
GPT–6 Astraxhigh100.0%$149.16
Claude Fable 5.1xhigh100.0%$140.88
Grok 4.6xhigh100.0%$16.05
Claude Opus 5xhigh0.0%$121.90
GPT–5.6 Solxhigh0.0%$29.06
Gemini 3.8 Flashhigh0.0%$5.85
0%50%100%

Run progress

Elapsed time from task receipt. Milestones use published annotations or the first matching recorded Facility action. A red × marks when a run stopped, at its last reached milestone.

Task receivedProtocol execution startedPowder and liquid transferredLC–MS acquiredEnd of recorded run02h4h6h8.4hElapsed time / hoursClaude Opus 5 · Task received: 0m; 1/1 attemptsClaude Opus 5 · Protocol execution started: 38m; 1/1 attemptsClaude Opus 5 · Powder and liquid transferred: 54m; 1/1 attemptsClaude Opus 5 · LC–MS acquired: 2h 43m; 1/1 attemptsClaude Opus 5 · End of recorded run: 6h 45m; 1/1 attempts11.1 %GPT–5.6 Sol · Task received: 0m; 1/1 attemptsGPT–5.6 Sol · Protocol execution started: 37m; 1/1 attemptsGPT–5.6 Sol · Powder and liquid transferred: 45m; 1/1 attemptsGPT–5.6 Sol · LC–MS acquired: 2h 34m; 1/1 attemptsGPT–5.6 Sol · End of recorded run: 3h 40m; 1/1 attempts0.2 %Claude Fable 5.1 · Task received: 0m; 1/1 attemptsClaude Fable 5.1 · Protocol execution started: 1h 08m; 1/1 attemptsClaude Fable 5.1 · Powder and liquid transferred: 1h 49m; 1/1 attemptsClaude Fable 5.1 · LC–MS acquired: 2h 54m; 1/1 attemptsClaude Fable 5.1 · End of recorded run: 8h 22m; 1/1 attempts45.6 %GPT–6 Astra · Task received: 0m; 1/1 attemptsGPT–6 Astra · Protocol execution started: 19m; 1/1 attemptsGPT–6 Astra · Powder and liquid transferred: 37m; 1/1 attemptsGPT–6 Astra · LC–MS acquired: 4h 32m; 1/1 attemptsGPT–6 Astra · End of recorded run: 7h 18m; 1/1 attempts25.2 %Gemini 3.8 Flash · Task received: 0m; 1/1 attemptsGemini 3.8 Flash · Protocol execution started: 33m; 1/1 attemptsGemini 3.8 Flash · Powder and liquid transferred: 46m; 1/1 attemptsGemini 3.8 Flash · LC–MS acquired: 1h 51m; 1/1 attemptsGemini 3.8 Flash · End of recorded run: 2h 35m; 1/1 attempts0.0 %Grok 4.6 · Task received: 0m; 1/1 attemptsGrok 4.6 · Protocol execution started: 26m; 1/1 attemptsGrok 4.6 · Powder and liquid transferred: 32m; 1/1 attemptsGrok 4.6 · LC–MS acquired: 1h 05m; 1/1 attemptsGrok 4.6 · End of recorded run: 2h 01m; 1/1 attempts44.5 %

Model trajectories

Run grading

Fail
MeasurementRecorded resultOutcome
Calibrated yield4.08 %× Fail

Pass condition: The calibrated amide yield must reach at least the human baseline (6.13%) within the three-minute reaction limit. An attempt that exceeds the time limit fails.

Maximize amide synthesis yieldClaude Opus 5 xhigh
Run gradingFail
00:0000:01

Model activity

Model transcript

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Appendix

Shared amide-synthesis equipment and materials, with the DMSO/formic-acid diluent required for calibrated yield measurement.

Main equipment2 items
Opentrons

Opentrons Flex Robot

OPENTRONS:999-00191

Automated liquid handling and deck orchestration

Waters

ACQUITY UPLC H-Class with QDa and PDA

WATERS:176003208

Liquid chromatography with mass and UV detection

Supporting equipment10 items
ItemBrandSKURole
Scout SPX223 AM Portable Precision BalanceOHAUSOHAUS:30253018Weigh reagents and prepared solutions.
Picus 2 Pipette, 100–5,000 µLSartoriusSARTORIUS:LH-747101Stock and source-vial preparation
Analog Vortex Mixer, 120 VFisherbrandTHERMO-FISHER:02215414Dissolution of the p-toluic acid and HATU stocks
Picus 2 Electronic Single Channel Pipette (500-10000 uL)SartoriusSARTORIUS:LH-747111Transfer measured volumes of reagents and samples.
Picus 2 Pipette, 5–120 µLSartoriusSARTORIUS:LH-747041Manual preparation of the LC–MS diluent
Picus 2 Electronic Single Channel Pipette (50-1000 uL)SartoriusSARTORIUS:LH-747081Transfer measured volumes of reagents and samples.
Deep Well Plate Adapter for Heater-ShakerOpentronsOPENTRONS:991-00066Secures the reaction plate on the Heater-Shaker
Heater-Shaker Module, Flex configurationOpentronsOPENTRONS:991-00115-FL-UNActivation, reaction, and dilution mixing
Flex 1-Channel Pipette, 5–1,000 µLOpentronsOPENTRONS:999-00187Reaction, control, and analytical-sample transfers
Flex Gripper GEN1OpentronsOPENTRONS:999-00194Plate and lid movement
Consumables7 items
ItemBrandSKURole
Flex Tips, 1,000 µL, filteredOpentronsOPENTRONS:991-00106Automated liquid transfers
96-well deep-well plate, V-bottom, 2 mLNESTNEST:503501Reactions, no-HATU control, and LC–MS samples
Tough Universal LidOpentronsOPENTRONS:999-00261Covers the plate during mixing
SafetySpace filter tips, 2–120 µLSartoriusSARTORIUS:790101FManual low-volume transfers
Optifit tips, 100–5,000 µLSartoriusSARTORIUS:780304Manual stock and source-vial transfers
Clear glass vial with cap, 15 mLUlineULINE:S-25276CHATU stock and reagent source vessels
ACQUITY UPLC BEH C18 column, 2.1 × 100 mm, 1.7 µmWatersWATERS:186002352LC–MS separation
Reagents9 items
ItemBrandSKURole
p-Toluic acid, 98%ChEBI 36635 Sigma-AldrichSIGMA-ALDRICH:T36803-500GCarboxylic-acid substrate; prepared as a 650 mM stock in DMF
Butyric acid, 99%+ChEBI 30772 Thermo Fisher ScientificTHERMO-FISHER:L13189.APCarboxylic-acid substrate
HATU, 97%PubChem 6409673 Sigma-AldrichSIGMA-ALDRICH:445460Coupling reagent; prepared as a 107.333 mg/mL stock in DMF
N,N-Diisopropylethylamine, ≥99%ChEBI 193590 Sigma-AldrichSIGMA-ALDRICH:D125806Base
Benzylamine, 99%ChEBI 40538 Thermo Fisher ScientificTHERMO-FISHER:105855000Amine substrate
Cyclohexylamine, 99%ChEBI 15773 Thermo Fisher ScientificTHERMO-FISHER:111280010Amine substrate
N,N-Dimethylformamide, 99.9%ChEBI 17741 Thermo Fisher ScientificTHERMO-FISHER:447090025Stock and reaction solvent; no-HATU control
Formic acid, Optima LC/MS gradeChEBI 30751 Fisher ChemicalTHERMO-FISHER:A11750LCMS diluent additive: 0.1% by volume in DMSO.
Dimethyl sulfoxide (DMSO)Thermo Fisher ScientificTHERMO-FISHER:348440010LCMS diluent: 99.9% by volume, with 0.1% formic acid; required by the yield calibration.