| HS Code | 541715 |
| Product Name | tert-Butyl Cyanoacetate |
| Iupac Name | tert-butyl 2-cyanoacetate |
| Cas Number | 1116-98-1 |
| Molecular Formula | C7H11NO2 |
| Molecular Weight | 141.17 g/mol |
| Appearance | Colorless to pale yellow liquid |
| Density | 0.987 g/mL at 25 °C |
| Boiling Point | 107-108 °C at 10 mmHg |
| Flash Point | 88 °C |
| Refractive Index | n20/D 1.419 |
| Solubility | Slightly soluble in water; soluble in common organic solvents |
| Storage Conditions | Store under inert gas at 2-8 °C |
| Synonyms | Cyanoacetic acid tert-butyl ester; tert-Butyl 2-cyanoacetate |
| Smiles | CC(C)(C)OC(=O)CC#N |
| Inchi | InChI=1S/C7H11NO2/c1-7(2,3)10-6(9)4-5-8/h4H2,1-3H3 |
| Purity | Typically ≥98% |
As an accredited Tert-Butyl Cyanoacetate factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.
| Packing | Tert-Butyl Cyanoacetate is supplied in a 100 g amber glass bottle with a PTFE-lined cap, sealed for safe storage. |
| Container Loading (20′ FCL) | Container Loading (20′ FCL): Tert-Butyl Cyanoacetate packed in drums, palletized, secured, and labeled inside a 20-foot container for export. |
| Shipping | Tert-Butyl Cyanoacetate is shipped as UN 3276, Nitriles, liquid, toxic, n.o.s. (tert-butyl cyanoacetate), Class 6.1, Packing Group III. It requires UN-approved packaging, toxic labels, and proper shipping papers. Keep containers closed, away from heat, oxidizers, and moisture; follow IATA, IMDG, and ADR regulations. |
| Storage | Store Tert-Butyl Cyanoacetate in a cool, dry, well-ventilated area away from heat, sparks, and open flames. Keep containers tightly closed and protected from moisture. Use appropriate flammable-liquid storage cabinets. Segregate from strong oxidizing agents, acids, and bases. Handle under inert gas if required. Ensure secondary containment and proper labeling. Keep away from food, drink, and incompatible materials. |
| Shelf Life | Stable for at least 12 months when stored tightly sealed in a cool, dry, well-ventilated place, away from moisture and heat. |
In pharmaceutical intermediate manufacture, tert-butyl cyanoacetate (CAS 1116-98-9) is charged as a protected active methylene donor in Knoevenagel condensations with substituted benzaldehydes and heteroaromatic aldehydes. A production-scale cycle typically uses 1.00 mol aldehyde, 1.15–1.30 mol tert-butyl cyanoacetate, 0.08–0.12 mol piperidine, and 0.10–0.14 mol acetic acid in 8.0–10.0 L cyclohexane per mol aldehyde inside a 3,000–5,000 L glass-lined reactor equipped with a retreat-curve impeller and a Dean-Stark trap. The batch is held at 80–82°C for 8–14 h until the water of condensation is collected, and conversion is monitored by GC-FID area percent after cold split injection. The resulting benzylidene cyanoacetate is concentrated at 45–55°C under 50–80 mbar vacuum, then crystallized from n-heptane at 0–5°C and discharged through a pressure nutsche. The tert-butyl ester group resists premature hydrolysis during subsequent heterocycle formation; downstream treatment with substituted hydrazines in ethanol at 20–40°C yields pyrazole and pyrazoline carboxylate intermediates that enter pharmaceutical synthesis routes. Residual solvent control for pharmaceutical intermediates aligns with ICH Q3C Class 2 limits of 890 ppm for toluene and 3,880 ppm for cyclohexane, while water content is determined by ISO 760. Terminal products from this application track include 5-substituted pyrazole building blocks, β-keto nitrile derivatives, and protected amino acid precursors. Published data for individual drug candidates based on this specific tert-butyl ester is limited because most dossiers disclose the final active pharmaceutical ingredient rather than early-stage protected intermediates.
| Control parameter | Method or standard | Limit |
|---|---|---|
| Assay | GC-FID area normalization | ≥ 98.0 area% |
| Water | ISO 760 | ≤ 0.10 wt% |
| Free cyanoacetic acid | Acid-base titration | ≤ 0.5 wt% |
| Toluene | ICH Q3C Class 2 | ≤ 890 ppm |
| Cyclohexane | ICH Q3C Class 2 | ≤ 3,880 ppm |
The kinetic penalty imposed by the branched tert-butyl ester is most significant when ortho-substituted aromatic aldehydes are used, because the ester group restricts approach of the secondary amine catalyst to the carbonyl carbon and slows formation of the enamine intermediate. Direct production-scale kinetic comparisons for tert-butyl cyanoacetate are not extensively published; process qualification campaigns therefore rely on statistically designed experiments to set catalyst loadings and hold times. In a representative hindered-substrate run, a piperidine loading of 0.05 mol per mol aldehyde can leave conversion below 95.0 area% after 6 h, whereas the same substrate with a linear ester may exceed 98.0 area% in 6–8 h. Raising catalyst loading to 0.15–0.20 mol accelerates conversion but increases the risk of Michael addition of piperidine to the benzylidene intermediate, which generates colored oligomeric material and reduces filtration rates on production filters. The practical processing window is therefore narrow: catalyst loading is held at 0.08–0.12 mol, reaction temperature is maintained at 80–82°C by cyclohexane reflux, and incremental additions of 0.02–0.03 mol pyrrolidine are used only when conversion plateaus. Water removal is critical because the Knoevenagel reaction is reversible; Dean-Stark operation must return dried cyclohexane to the reactor, and residual water in the solvent should be below 0.05 wt% by ISO 760. A rise in reaction temperature above 82°C through addition of toluene or xylene accelerates aldehyde consumption but also increases higher-molecular-weight byproducts, which complicates downstream crystallization and lowers isolated yield. The terminal products from this hindered ester route are substituted benzylidene cyanoacetates that serve as intermediates for heterocyclic active ingredients; ester-specific adoptions are usually justified when the downstream process requires acid-labile ester protection during alkaline work-up sequences.
Selective removal of the tert-butyl group without cleavage of the nitrile function is performed under anhydrous acidolytic conditions in fine chemical and pharmaceutical intermediate campaigns. A typical charge includes 1.00 mol tert-butyl cyanoacetate derivative dissolved in 5.0–8.0 L dichloromethane per mol substrate, cooled to 0–5°C under nitrogen in a glass-lined reactor with a brine jacket capable of maintaining −10 to −5°C during the initial exotherm. A solution of 2.5–5.0 mol hydrogen chloride in 4 M dioxane is added over 1–2 h while the internal temperature is kept at 0–10°C, followed by holding at 20–25°C for 4–6 h. The acidolysis releases 1.0 mol isobutylene per mol ester; at 25°C this occupies approximately 24.5 L per mol, and the reactor vent is routed through a caustic scrubber containing 20–25 wt% aqueous sodium hydroxide to remove isobutylene and residual acid vapours. Water is excluded because water promotes ester hydrolysis and can create a two-phase reaction mixture that reduces selectivity; the solvent and acid reagent are predried to 0.10 wt% water or less by ISO 760. After reaction completion, the mixture is quenched into ice water, extracted with dichloromethane, dried over magnesium sulfate, and concentrated at 40–50°C and 20–30 mbar vacuum. The resulting cyanoacetic acid derivative or cyanoacetic acid salt is typically isolated in 95–99 area% purity by GC-FID or HPLC area normalization. Residual dioxane is controlled to the ICH Q3C Class 2 limit of 380 ppm because dioxane is used as the acid carrier, while the process is operated under the quality expectations of ICH Q7 for active pharmaceutical ingredient intermediates. The terminal products are deprotected cyanoacetate building blocks used in subsequent amidation, salt formation, or cyclization steps. This route is incompatible with primary or secondary amines and with alcoholic solvents that can re-esterify the liberated acid under acidic conditions.
Agrochemical intermediate production employs tert-butyl cyanoacetate as a sterically shielded methylene source when the ester must survive condensation and hydrogenation sequences without premature hydrolysis. The first step is a Knoevenagel condensation between 4-substituted benzaldehydes and 1.05–1.20 mol tert-butyl cyanoacetate per mol aldehyde in cyclohexane or n-heptane at reflux, with a catalytic mixture of piperidine and acetic acid. After phase separation and solvent exchange, the intermediate is hydrogenated over Raney nickel or supported palladium in tetrahydrofuran at 25–40°C and 0.5–1.0 MPa hydrogen pressure to give saturated β-amino ester intermediates. The reactor is typically a hydrogenation autoclave with a gas-inducing impeller, and the catalyst loading is maintained at 5–10 wt% relative to substrate. During work-up, the organic phase is washed with dilute sodium bicarbonate at pH 8.0–8.5, a condition under which the tert-butyl ester is significantly more resistant to hydrolysis than methyl or ethyl esters. The product stream is then polished by vacuum distillation at 50–80°C and 1–10 mbar to remove low-boiling impurities. Terminal products from this track are β-amino acid ester building blocks and substituted cyanoacetate intermediates that enter crop protection discovery and development programs; specific actives using the tert-butyl ester are not routinely identified in public registration dossiers because the ester is often transformed before the final active ingredient is declared.
Tert-butyl cyanoacetate can be condensed with paraformaldehyde under base catalysis to yield oligomeric poly(tert-butyl cyanoacrylate), which is then thermally depolymerized to release the corresponding cyanoacrylate monomer. The condensation uses 1.00 mol tertiary ester and 1.00–1.10 mol formaldehyde equivalent in the presence of a secondary amine catalyst, with water removed by azeotropic distillation. The resulting oligomer is fed through a wiped film evaporator at 180–220°C and 1–5 mbar absolute pressure, where the monomer is recovered as a vapour and condensed into a stabilizer-containing receiver. The bulky tertiary ester side chain slows anionic polymerization relative to ethyl cyanoacrylate, making the monomer less responsive to initiators at ambient temperature; published lap-shear data for tert-butyl cyanoacrylate on standardized metal coupons is limited, and industrial validation under ASTM D1002-10 would be required before adhesive qualification. Stabilizer systems for this monomer type must be established by inhibitor screening; typical loads for cyanoacrylate monomers are measured in the 10–100 ppm range, but the exact level for the tert-butyl analogue depends on residual water and acid content in the monomer. The terminal product is a low-volatility cyanoacrylate monomer that may be evaluated where slower surface-initiated cure is acceptable, although technical adoption in high-speed metal bonding is limited compared with ethyl, methoxyethyl, and 2-ethylhexyl homologues. Production equipment must be electrostatically grounded because monomer vapour can deposit and polymerize in vacuum lines; cold traps and line heat-tracing at 40–60°C are used to prevent plugging before the receiver.
In UV absorber and functional coating intermediate synthesis, tert-butyl cyanoacetate is used as the cyanoacetate donor in condensation with diaryl ketones to produce α-cyano-β,β-diarylacrylate structures analogous to octocrylene chemistry. The reaction is carried out in xylene at 140–145°C for 12–18 h using ammonium acetate at 0.15–0.25 mol per mol ketone and a slight molar excess of the tertiary ester at 1.20–1.40 mol per mol ketone. Water is removed by azeotropic distillation, and the crude product is washed with water and dilute sodium chloride, dried, and then crystallized from isopropanol or methanol. The crystalline intermediate is isolated by filtration and vacuum-dried at 40–50°C and 10–30 mbar to reduce solvent retention. Purity is controlled by HPLC at 254 nm with area normalization, and residual solvent limits follow standard chemical supplier specifications. The tert-butyl ester imparts different solubility and volatility characteristics compared with the 2-ethylhexyl analogue used in sunscreen-grade octocrylene; published comparative migration and photostability data for this specific tert-butyl derivative is limited. Terminal products from this application are ester-controlled cyanoacrylate UV absorber intermediates and functional coating additives for evaluation in industrial polymer matrices where lower ester volatility is required during processing.
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Tert-butyl cyanoacetate, CAS 1116-98-9, is the 1,1-dimethylethyl ester of cyanoacetic acid, with molecular formula C7H11NO2 and molar mass 141.17 g·mol⁻¹. The molecule combines an active methylene carbon flanked by nitrile and tert-butoxycarbonyl groups; this arrangement retains the nucleophilic reactivity of cyanoacetate esters while replacing linear alkyl ester substituents with a tertiary alkyl group. Commercial material is supplied as a clear to pale-yellow liquid in two common grade bands. Technical-grade lots are specified at ≥98.0% assay by GC-FID area normalization, with moisture ≤0.10% by Karl Fischer titration conforming to ASTM E203, and high-purity pharmaceutical-intermediate lots are controlled to ≥99.0% GC assay. The tert-butyl ester is not a single-model product in the polymer-resin sense; grade differentiation arises from residual water, titratable acidity, and color rather than molecular architecture. Because the compound is used as a building block in route scouting and registered intermediate manufacturing, batch-to-batch consistency in moisture and acidity is more process-critical than nominal assay alone.
In pilot-scale syntheses, tert-butyl cyanoacetate is transferred through stainless steel or glass-lined equipment with PTFE seals. The measured density is approximately 1.02 g/mL at 25 °C, which permits volumetric metering when mass-flow cells are unavailable; however, moisture ingress during drum discharge changes Karl Fischer values before GC assay shifts. Refractive index, reported near 1.420 for n20D, can serve as rapid identity verification when referenced against the supplier lot certificate. Distillation for specification recovery is executed under reduced pressure with a boiling range reported near 107–108 °C at 24 mmHg; vacuum source capacity must account for the low vapor pressure and avoid localized overheating above 120 °C, where thermal elimination of isobutylene may reduce recovery.
The tertiary ester substituent is not merely a protecting group; it changes the steric and electronic environment at the carbonyl and the adjacent active methylene. In Knoevenagel condensations with aromatic aldehydes run in toluene or dioxane at 70–90 °C using piperidinium acetate or ammonium acetate, tert-butyl cyanoacetate gives the corresponding α-cyanoacrylates with less competitive amide formation than methyl or ethyl cyanoacetate. The lower susceptibility to nucleophilic attack at the ester carbonyl arises from steric hindrance at the tert-butyl oxygen-bearing carbon. Stoichiometric ratios of aldehyde to tert-butyl cyanoacetate are typically maintained at 1:1.0 to 1:1.2 to compensate for the slightly reduced enolate formation rate. In continuous-flow equipment with perfluoroalkoxy tubing and residence times of 10–30 min, conversions above 90% have been reported for selected aryl aldehydes, though published data for specific catalyst loadings is limited.
Process control is centered on the base-sensitive self-condensation of the active methylene component. The practical operating window is often set at 80 °C ± 5 °C for piperidinium acetate catalysis: lower temperatures give incomplete conversion within the desired batch time, while higher temperatures raise color and oligomer content. Water removal is the dominant kinetic variable in toluene reflux systems; Dean–Stark traps are run until the collected water is ≤0.2% of the reaction mass. On a 500–2,000 L glass-lined reactor, the aldehyde and catalyst are commonly charged in toluene first, followed by slow addition of tert-butyl cyanoacetate at 80 °C over 60–90 min. This addition order limits the concentration of the unreacted active methylene compound under base, reducing self-condensation oligomer formation. Published data for this specific configuration is limited to route descriptions, and exact conversion varies with aldehyde electronics.
Specification sheets for tert-butyl cyanoacetate are less standardized than those for commodity acrylate esters, and the absence of a unified pharmacopoeial monograph places analytical burden on the receiving quality unit. At incoming inspection, identity is commonly confirmed by FTIR against a reference spectrum and by GC retention time using a 30 m × 0.25 mm × 0.25 µm 5%-phenyl methylpolysiloxane capillary column. The nitrile stretch appears near 2260 cm⁻¹, and the ester carbonyl appears near 1740 cm⁻¹. Water content is determined by Karl Fischer coulometry per ASTM E203; values below 0.05% are required when the ester is used in enolate chemistry with alkoxide bases, because residual water quenches alkoxide equivalents and creates hydroxide, which hydrolyzes the ester to cyanoacetic acid and tert-butanol. Color is controlled by APHA/Pt-Co per ASTM D1209; a value above 50 usually indicates thermal history or air oxidation and may correlate with non-volatile residue. Titratable acidity is reported as cyanoacetic acid and is relevant because free acid alters stoichiometry in base-sensitive condensations.
The following comparison uses representative physical-property values from supplier certificates and public safety data sheets; they are not unified specifications but distinguish the tert-butyl ester from its lower homologues.
| Ester | CAS | Molar mass (g·mol⁻¹) | Density at 25 °C (g/mL) | Boiling range | Steric class |
|---|---|---|---|---|---|
| Methyl cyanoacetate | 105-34-0 | 99.09 | 1.123 | 203–205 °C at 760 mmHg | primary |
| Ethyl cyanoacetate | 105-56-6 | 113.11 | 1.062 | 208–210 °C at 760 mmHg | primary |
| Tert-butyl cyanoacetate | 1116-98-9 | 141.17 | 1.02 | 107–108 °C at 24 mmHg | tertiary |
Typical incoming acceptance checks for high-purity lots are summarized below. The limits are common commercial criteria, not regulatory specifications, and should be verified against the current supplier certificate.
| Parameter | Test method | Typical acceptance criterion |
|---|---|---|
| Assay | GC-FID area percent | ≥99.0% |
| Water | ASTM E203 Karl Fischer | ≤0.05% |
| Color | ASTM D1209 APHA/Pt-Co | ≤50 |
| Titratable acidity | Titration as cyanoacetic acid | ≤0.10% |
| Refractive index n20D | Abbé refractometer | 1.419–1.423 |
Additional identity confirmation is obtained by ¹H NMR in CDCl3: the tert-butyl group appears as a sharp singlet near δ 1.50 with integration 9H, and the active methylene appears near δ 3.44 with integration 2H. In GC-FID purity methods, the tert-butyl ester elutes later than methyl and ethyl cyanoacetate under the same oven program; this retention shift permits rapid detection of wrong ester inventory. In electron-impact mass spectra, the molecular ion near m/z 141 is weak, and the fragment from loss of isobutylene near m/z 85 is more prominent. These spectral features support lot-to-lot identity verification in pharmaceutical intermediate laboratories without relying solely on retention time.
In pharmaceutical intermediate manufacturing, tert-butyl cyanoacetate is selected over methyl or ethyl cyanoacetate when downstream chemistry requires a carboxylic acid protected as a tert-butyl ester that can be cleaved under acidolysis without saponification of the nitrile. The tert-butyl ester tolerates neutral and mildly basic conditions better than methyl ester but is cleaved under anhydrous acid conditions, such as 4 M HCl in dioxane or trifluoroacetic acid in dichloromethane at 0–25 °C. This selectivity is operationally important in routes where the nitrile is retained as a synthetic handle. For example, a Knoevenagel adduct prepared from tert-butyl cyanoacetate can undergo conjugate addition or selective reduction at the nitrile while the ester remains intact; subsequent acid-mediated tert-butyl cleavage releases isobutylene gas and the free acid. Engineering controls for acid deprotection vessels must include caustic scrubber capacity for isobutylene and temperature ramps below 35 °C to avoid uncontrolled exothermic gas evolution.
Production-scale Knoevenagel reactions with tert-butyl cyanoacetate are frequently run in glass-lined reactors of 500–2,000 L capacity equipped with Dean–Stark traps when toluene azeotropic water removal is required. The aqueous phase generated during piperidinium acetate-catalysed condensations is removed overhead at 85–110 °C; residual water in the distillate is monitored by Karl Fischer analysis of the trap contents, with a target below 0.2% before reflux is terminated. In a typical quench protocol, the cooled reaction mass is washed with 5% aqueous sodium chloride and the organic layer is dried over anhydrous sodium sulfate. This washing step is preferred over aqueous bicarbonate washes, which can raise interfacial pH high enough to attack the tert-butyl ester. Equipment for drum charging and reactor transfer should be nitrogen-inerted; the use of gear pumps with flooded suction is preferred over diaphragm pumps when transferring high-purity lots because low shear and minimal vapor formation preserve moisture specifications.
In practical terms, the product differs from methyl cyanoacetate and ethyl cyanoacetate in four operational dimensions: nucleophilic susceptibility at the ester carbonyl, thermal elimination behavior, water tolerance, and analytical retention time. Methyl cyanoacetate is more prone to ammonolysis and transesterification because the unhindered methyl ester carbonyl is accessible. Ethyl cyanoacetate offers lower cost per mole but generates ethanol during ester cleavage, which can complicate solvent recovery in azeotropic systems. The tert-butyl ester generates isobutylene, a gas that can be vented to a thermal oxidizer or scrubber, reducing aqueous organic load. Conversely, tert-butyl cyanoacetate has a higher molar mass and therefore lower active methylene content per kilogram: 7.09 mol·kg⁻¹ compared with 10.09 mol·kg⁻¹ for methyl cyanoacetate and 8.84 mol·kg⁻¹ for ethyl cyanoacetate. This lower molar activity must be factored into batch cost calculations and equipment loading.
Tert-butyl cyanoacetate is stable under recommended storage at 2–8 °C under inert gas; however, prolonged contact with atmospheric moisture slowly hydrolyzes the ester linkage, generating cyanoacetic acid and tert-butanol. Cyanoacetic acid is corrosive to carbon steel and can promote rusting in drum interiors if breather vents are inadequate. The compound should be segregated from strong bases, aqueous alkali, and primary or secondary amines. Amine contact can lead to amide formation and heat release, particularly with primary amines such as monoethanolamine and ethylenediamine, which react at the ester carbonyl and should be excluded from storage and cleaning procedures. Storage tanks and transfer lines in dedicated plants are typically 304L stainless steel or glass-lined carbon steel; copper and copper alloys are avoided because trace copper accelerates oxidative discoloration of cyanoacetate esters.
Under prolonged heating above 120 °C, tert-butyl cyanoacetate may undergo retro-ene elimination to isobutylene and cyanoacetic acid, and atmospheric distillation should be avoided. Flash point data in supplier SDS vary by test method and purity; closed-cup values reported near 91 °C place the material above the flammable liquid cutoff in many jurisdictions but still require careful earthing during drum transfers because static accumulation in low-conductivity organic liquids can initiate flash fires if vapor space is in the flammable range. Bonding and grounding cables with resistance below 1 × 10⁶ Ω per NFPA 77 are applied during all transfers. Importers in the EU are required to register the substance under REACH when annual tonnage exceeds 1 tonne, and an extended safety data sheet with exposure scenarios is required for industrial use.
