Tracing the development of modern organic synthesis, one stumbles into a world where small molecular tweaks cause seismic shifts in function. The journey toward synthesizing aryl triflates, like Trifluoromethanesulfonic acid 4-(trans-5-propyl-tetrahydropyran-2-yl)-phenyl ester, follows decades of trial and error in the hopes of making better leaving groups, facilitating more efficient cross-coupling reactions, streamlining medicinal chemistry campaigns. Early chemists weren’t aiming to please analytical chemists with fancy names; they wanted simplified routes, more predictable transformations, fewer headaches with purification. The introduction of triflate esters into the synthetic chemist’s toolbox meant fewer annoying byproducts, more confident predictions when running cross-couplings or nucleophilic aromatic substitutions, and new ground for drug designs. Today’s relatively intricate derivatives—adorned with propyl and tetrahydropyranyl segments—stand tall on the shoulders of this persistent innovation, built for tough challenges in chemo- and site-selectivity.
As the name suggests, this compound bridges several structural features: a phenyl core linked to a robust trifluoromethanesulfonate, but it doesn’t stop there. The tetrahydropyran ring, locked in its trans configuration with a propyl tail at position 5, contributes added stability and lipophilicity, augmenting both synthetic value and the potential for biological evaluation. For the everyday synthetic chemist, these kinds of molecules feel custom-built for Suzuki, Stille, or Buchwald-Hartwig reactions, often outperforming more pedestrian aryl bromides or iodides in both reliability and purity of products. Chemical suppliers know this customer group well, and they stock such molecules with careful documentation, keeping standards high to match regulatory needs and experimental rigor.
In the lab, properties dictate workflow. This ester emerges as a crystalline solid, notable for its white to off-white appearance that instantly signals the absence of colored impurities. Its melting point hovers in a generous range, comfortably above room temperature to allow for stable storage but low enough to avoid the fire safety worries of some organic peroxides. The molecule resists hydrolysis under ambient humidity, owing to the electron-withdrawing triflate and the shielding offered by the tetrahydropyranyl ring. Its solubility spreads across polar aprotic solvents—dimethyl sulfoxide, acetonitrile, dichloromethane—giving flexibility to those running reactions without solvent limitations. Triflated esters stand as heavy hitters for reactivity, pushing stubborn aryls through tough coupling reactions by stabilizing negative charge efficiently as the triflate leaves.
Buyers expect specificity, and suppliers answer with certificates of analysis, detailing content by weight (often quoted as a minimum of 98% purity by HPLC), water content as assessed by Karl Fischer titration, and residual solvent assessments matching ICH Q3C standards. Product vials carry hazard pictograms, precautionary and hazard statements per GHS alignment, and batch numbers for full traceability. Labels delivered in internationally recognized formats, with chemical formula and structure front and center for immediate reference, reduce confusion, especially in busy shared labs. The analytical data sheets go so far as to include NMR spectra (¹H, ¹³C, and ¹⁹F), IR spectra, and mass spec, giving end-users the confidence and agility to jump right into synthesis.
The synthetic route often begins with the preparation of the substituted phenol, introducing the tetrahydropyranyl ring via acid-catalyzed cyclization of an appropriate diol, then tacking on the propyl group under Friedel–Crafts alkylation or transition-metal catalyzed coupling. To install the all-important triflate, chemists expose the purified phenol to trifluoromethanesulfonic anhydride in the presence of a base like pyridine or triethylamine, running the reaction under anhydrous conditions to stave off all encroaching water from hydrolyzing the reactive intermediate. This step demands careful temperature control—chilling in an ice bath, slow anhydride addition, dry glassware—because this chemistry tends to escalate if rushed. Workups involve careful quenching, extraction into organic solvents, and drying over magnesium sulfate before a final flash chromatography to ensure absolute purity.
This ester doesn’t just sit quietly on the shelf; it’s built for transformation. The triflate is a king among leaving groups, giving even the most hindered or electron-rich aryl electrophiles a fair shot at successful coupling. Suzuki-Miyaura reactions snap into high gear with this electrophile, especially when targeting biaryl bonds. Stille or Negishi couplings, often sensitive to competing nucleophiles, benefit from the clean, rapid displacement offered by the triflate. The tetrahydropyranyl group can be further manipulated as a synthetic handle or protecting group; acid treatment removes it with minimal fuss, liberating the underlying aryl for further functionalization. These modifications let chemists race through retrosynthetic plans, opening doors to new medicinal scaffolds or complex materials more quickly than with conventional aryl halides.
Over the years, this compound appears in catalogs and journals under various aliases, reflecting both structure and functionality. Names like “4-Trifluoromethanesulfonoxy-(trans-5-propyl-tetrahydropyran-2-yl)benzene”, “(trans-5-Propyl-tetrahydropyran-2-yl)phenyl triflate”, and more cryptic registry numbers—such as CAS identifiers—populate the literature and procurement systems. These names help locate the right product, yet often require a chemist’s eye to spot subtle shifts that signal a related analog rather than the exact compound in question. Keeping standardized nomenclature helps track regulatory filings, patent coverage, and synthetic literature—crucial for anyone scaling up for clinical studies or specialty applications.
Real-world handling walks a line between reactivity and operator safety. The triflate moiety brings acute hazards if inhaled or exposed to skin, owing to its strong electrophilicity and irritant properties. Lab safety data sheets call for gloves, goggles, and fume hoods; real-life scenarios see chemists prepping reactions in ventilated enclosures and quickly locking away vials after each use. Despite its chemical stability for storage, the triflate doesn’t take kindly to exposure to bases or strong nucleophiles outside controlled reactions. Disposal follows local hazardous waste protocols, not just for environmental compliance but to avoid unintended run-ins with drains or landfill leachate.
In industry and academia, these esters power up drug development, agrochemical synthesis, and even advanced materials research. Medicinal chemists love the ability to swing new aryl groups into late-stage molecules that resist most other routes. Triflates turn up in fragment-linking strategies for kinase inhibitors and neuroactive molecules; they also underpin custom ligands and polymers where purity can’t be sacrificed. For those in radiochemistry, these triflated precursors serve as handy launchpads for isotope labeling, thanks to their predictable reactivity with nucleophilic [¹⁸F]fluoride or aryl lithiums.
Across pharmaceutical pipelines, this particular compound serves a niche yet growing demand. Newer drug candidates increasingly call for nontraditional substitution patterns, and the combination of a robust triflate leaving group with a hydrophobic, sterically secure trans-5-propyl-tetrahydropyran ring fits the bill. This structural ensemble lets scientists evaluate SAR (structure-activity relationship) trends by quickly swapping groups using palladium-catalyzed chemistry. R&D teams commit time and resources to optimizing not just individual reactions but whole libraries of analogs, pushing towards compounds with tailored selectivity, metabolic stability, and bioavailability.
Because the core structure combines a strong acid derivative and a hydrophobic ring, toxicity research demands thorough attention. Studies report moderate skin and respiratory irritation in rodents, prompting clear risk assessments and careful workplace air monitoring. Chronic exposure data stays limited, so most protocols assume a worst-case scenario and adopt strict handling guidelines. Environmental fate studies show the triflate moiety persists under neutral or basic conditions, making waste management central to sustainable practices. For laboratory animals, short-term dosing produces signs of liver and kidney strain, but the compound doesn’t appear bioaccumulative in higher mammals, according to published ADME data.
Looking ahead, the landscape of synthetic chemistry keeps favoring efficiency and selectivity. As times change, the drive for greener methodologies and more sustainable reagents stands out. Researchers already experiment with milder triflation agents and recyclable catalysts in coupling chemistry. The core features of Trifluoromethanesulfonic acid 4-(trans-5-propyl-tetrahydropyran-2-yl)-phenyl ester will almost certainly see them pressed into service within flow chemistry and high-throughput, automated compound assembly. Integrating robust triflates into data-driven medicinal campaigns, driven by AI and machine learning platforms, signals a future of faster, safer compound iteration—balancing discovery with responsibility. Just as pioneers laid the ground for modern aryl triflate chemistry, the next wave looks set to push boundaries of efficiency, safety, and application.
Chemists have a love-hate relationship with some of the nastier reagents in their labs. Trifluoromethanesulfonic acid, often called triflic acid, has a sharp reputation for super-strong acidity—much stronger than regular sulfuric acid or even p-toluenesulfonic acid. When someone tells you their molecule features a triflate ester, you know they’re after reactivity that can open doors in synthesis, especially when they want to turn an alcohol group into a great leaving group.
Toss in the complexity of a 4-(trans-5-propyl-tetrahydropyran-2-yl)-phenyl group, and you’re no longer looking at textbook chemistry. You meet the sort of scaffold that medicinal chemists and organic researchers love to push to its limits. The main scene where this compound shines is in synthetic organic chemistry—especially for building and modifying molecules with a goal in mind, like making a new pharmaceutical candidate.
The big role of this triflate ester comes from its ability to turn a stubborn group like a phenol into something that wants to leave. If you ever tried to swap out an OH group for something else—say, a boronic acid (for Suzuki coupling), a cyanide (for aromatic nitrile synthesis), or even a simple methyl group—ordinary conditions will barely budge some phenols. Making the triflate ester changes the dynamics overnight. Suddenly, that compound springs into action, letting you make new carbon-carbon or carbon-heteroatom bonds with easy-to-handle reagents under gentler conditions.
In drug discovery, where little changes in molecular structure make big differences to a compound’s behavior, this kind of transformation is golden. Researchers want to tweak rings and side chains without rebuilding the core every time. Having a phenyl triflate handy lets them swap in new functional groups with a toolkit of well-established reactions: Suzuki, Sonogashira, Buchwald-Hartwig, and more. Each new step potentially steers a compound toward improved activity, stability, or safety.
Some chemical tools cut both ways. The power of triflic acid demands respect. Even seasoned lab workers gear up, because spills mean serious burns and damaged equipment. The high cost and reactivity mean people avoid using this reagent at a huge scale, reserving it for work that really needs it. The triflate esters themselves don’t stick around lightly; they break down if wet or exposed to base, so storing and using them takes extra care.
Turning a phenol into a triflate has never been a move for the faint-hearted, but it’s essential for making some modern drugs and advanced materials. Researchers in pharmaceutical and materials chemistry use such reactions for high-impact projects.
For all their usefulness, triflates and triflic acid still create waste and hazards that need careful attention. Companies and university labs keep searching for milder alternatives—new reagents that do a similar chemical job, but without the nastiness. Some success stories use milder sulfonates, more sustainable coupling partners, or even enzyme-based routes for tricky transformations.
From my own experience, working with triflates calls for respect, teamwork, and planning. We always made a real effort to use the smallest volumes, avoid unnecessary runs, and neutralize waste with care. Chemists keep looking for that sweet spot—maximum reactivity, minimum risk, and manageable waste. Finding safer, practical approaches is as important as making that next molecule.
Once you start working in a lab—especially in chemistry or pharmaceuticals—you realize that rules about where and how to store chemicals get written in blood. One time, someone neglected a hygroscopic reagent on an open shelf, and a week later, I watched dust and clumps ruin a thousand-dollar batch. Not all substances get that dramatic, but plenty still bring their own hazards, whether from fire risk, toxicity, or plain old instability.
Some compounds just don’t play nice with moisture in the air. Many kinds of salts, for instance, pick up water fast enough to make handling difficult and measuring a guessing game. Storing these in tightly sealed desiccators or containers with strong gaskets holds off the worst. Heat is another enemy: organic peroxides break down, and simple vitamins like vitamin C brown up and lose strength. Refrigerators set between 2°C and 8°C help extend shelf life, and freezers are gold for anything really unstable—just be sure labels never peel off.
Sunlight can break down certain compounds faster than expected. I’ve watched clear glass vials of silver salts turn black on a bright bench. Amber bottles solve a lot of these messes. Even in general storage, tucking light-sensitive bottles away from direct light sources keeps their potency for a longer time.
When handling flammable, reactive, or air-sensitive chemicals, regular air isn’t always safe. Solvents like diethyl ether or chloroform evaporate faster than you can blink, and just the residue can sometimes produce enough vapors to set off alarms or even ignite. Using fume hoods gives a simple safeguard. On another front, rare compounds like lithium aluminum hydride react dangerously when exposed to air or moisture. That’s where a glovebox flush with argon or nitrogen gas really earns its keep.
Mix acids with bases on a shelf and sooner or later, something leaks and there’s a corrosive mess. Keeping incompatibles apart feels annoying when you’re moving things around, but it really prevents accidents. In our lab, acids have one cabinet, bases are locked up in another, and oxidizers stay far from organic solvents. Color coding makes this easier; a simple sticker keeps costly mistakes at bay. And always—safety data sheets provide details that sometimes surprise even veterans.
Faded or missing labels spell disaster. Every bottle, vial, or tub in my fridge has a label with clear compound names, concentrations, preparation dates, and even expiration alerts. Digital inventories save time, but nothing beats a visible date right on the container. When a container reaches its toss date or the contents spoil, tossing it right away keeps clutter down and prevents awkward questions later.
Disposal plans should work for the worst day, not just the average one. Neutralizing acids and bases before pouring them down the drain keeps pipes safe. Volatile organics and heavy metals go into dedicated waste containers, which never mix. Many companies run pick-ups, or coordinate with hazardous waste facilities. Skipping a step here can mean fines or, worse, injuries. In one case, improper disposal of mercury once led to a month-long shutdown in the research wing.
Storage and handling guidelines don’t stay static. New compounds hit the market every year, and regulations grow stricter. Teams have to communicate, document, and adapt. Training sessions, posted charts, and honest conversations about past mistakes all build a safer workplace. In the end, attention to storage and handling doesn’t just protect chemicals—it keeps people safe, budgets on track, and research moving forward.
Chemical purity isn’t just a number on a sheet. It drives everything from safety in the lab to quality in manufacturing. Many people think purity ratings—95%, 98%, 99.9%—are all about getting the cleanest product possible. From my time in the field, I know those extra decimal points matter, especially for folks working with pharmaceuticals, electronics, or anything where even tiny impurities can ruin a process or trigger regulatory trouble.
Lab techs and quality managers keep an eye on those certificates of analysis, but not every supplier means the same thing by “pure.” The testing method, the sample size, and what gets labeled as an “impurity” all shift the story. High-performance liquid chromatography or gas chromatography can catch things that would slip by with less refined methods. Sometimes, what passes as pure in one country doesn’t fly elsewhere. This isn’t just paperwork. Cutting corners on purity can leave behind heavy metals or other toxic leftovers, threatening health and public trust.
Demand for top-purity chemicals keeps climbing, especially as industries demand stricter tolerances. For example, making semiconductors or vaccines takes chemicals so pure most people would struggle to imagine the standards. I’ve seen entire batches scrapped over impurities barely detectable to the naked eye, turning a tiny measurement into a multimillion-dollar problem. If you’re just cleaning glassware, purity might take a backseat. If you’re crafting lifesaving drugs, there’s no cutting corners.
Anyone who’s ever needed specialty chemicals knows the drill—one month the product seems plentiful, the next you’re chasing down suppliers for every last gram. Global supply chain hiccups, export controls, and shutdowns at production plants throw everything off, sometimes for months. Just last year, supply issues left research teams stalled, waiting for shipments that never came. No research gets done, deadlines get missed, and costs skyrocket.
Availability goes far beyond whether a website lists something as “in stock.” Suppliers may quote huge volumes, but in reality, quality product at scale can be rare. Larger manufacturers might lock down contracts, squeezing out smaller buyers. I’ve seen professors and small companies forced to turn to middlemen, paying premiums just to get started on a project.
Then there’s shelf life. Even if a supplier has large volumes, improper storage kills quality fast. Some chemicals degrade in days if not kept cold or away from air. All these details make a world of difference.
Reliable data matters. The best suppliers publish detailed analysis, update data sheets, and encourage third-party verification. You don’t just want to take their word for it. Independent labs confirm results and keep everyone honest. Supply transparency helps too. Sharing not just what’s available today, but production schedules, raw material source changes, and storage conditions, goes a long way toward building confidence.
There’s space for smart tech here. I’ve noticed blockchain tracking catch on for some critical chemicals, letting buyers trace shipment and purity data back to the source. This kind of accountability helps reduce counterfeits and keep standards high.
Finding a trustworthy supplier for high-grade chemicals remains a mix of technical know-how and old-fashioned relationship building. Real confidence comes from verified results, clear communication, and a shared drive for safety and quality. As industries raise the bar for purity, everyone from lab managers to end users wants to know not only how pure a product is, but if they can actually count on getting enough when it’s needed most.
Anyone who’s spent real time in a lab or a factory knows that a substance’s danger rarely makes headlines until something goes wrong. You can smell it, see it eat into gloves, or feel your skin tingle after a tiny spill. When companies ask about hazards, they’re not just chasing paperwork. They want people to go home with ten fingers, they want solid equipment that keeps working, and they want zero fines on the company books.
No two chemicals act alike, but some hazards keep showing up. Volatile fumes can do real damage to your lungs — anybody who’s wiped up a solvent spill without decent ventilation knows that headache feeling. Splash something acidic or caustic and watch nylon work gear dissolve like candy. Some powders or dusts won’t tease your nose, they’ll attack deep in your lungs. I’ve watched colleagues skip goggles “just this once,” then flush their eyes for a quarter hour. Shortcuts seem attractive until someone gets hurt—then it’s a mess for everyone.
Nobody loves the constant parade of gloves, masks, gowns, and face shields, but personal protection means more than avoiding blame. A good kit makes mistakes survivable. One old habit that saves more than anything: never assuming you know how a substance will react until you see the safety data sheet. Too many seasoned hands got burned by thinking, “Oh, this acts just like last month’s order.” Turns out, small tweaks in chemical structure or concentration can change risks drastically.
According to OSHA, over 50,000 workers die each year from long-term chemical exposure in the U.S. Thousands more face severe burns, blindness, or lung disease. These aren’t just statistics — every veteran can recall an accident that altered someone’s career overnight. Often, these came from overlooked warnings: drying your hands poorly before handling an exothermic agent, or stashing a reactive solid near water pipes.
Some safety habits demand repetition. Never mix or transfer chemicals without labeled containers. Always triple-check the compatibility chart on storage shelves. Keep spill kits close, not buried in a locked cabinet across the hall. Warn new hires to respect unfamiliar labels and to shout out when they’re unsure. In my early days, a supervisor pulled me aside after a near-miss and hammered this point: the crew’s safety is only as strong as the least prepared rookie. People grow to appreciate this, especially after they’ve used that eye-wash station in a panic once.
Facility managers and shift leaders need to stay current with hazard updates. Regulations change, suppliers switch ingredients, and yesterday’s safe bet can become today’s risk. Encourage routine audits, not as witch hunts, but as reality checks. Honest talk helps — sharing those ugly “no one got hurt, but almost” stories helps others build good habits. Fact is, nobody likes forced training, but everyone appreciates a colleague with an eye for hazards and a willingness to speak up. Making safety personal keeps people engaged and accidents rare.
Anyone who’s worked the bench in an organic lab remembers their first time fussing over which solvent would get their reaction to run. Solvent isn’t just fluid in the flask—it shapes how molecules bump together, whether things dissolve, if heat zips in or sneaks out. No matter how smart your design looks, the whole process pivots on that choice.
Solvent choice starts with the nature of the compounds you handle. Polar molecules dissolve best in polar solvents. Water handles ionic and hydrogen-bonding types, but most organic chemistry happens outside that playground. Ethanol and methanol jump in for things with some polarity—aldehyde reductions, SN1 reactions, that kind of work. Diethyl ether and tetrahydrofuran (THF) show up for Grignard reactions, not just because they dissolve magnesium salts, but because they never drown reactive intermediates with rogue protons.
I’ve seen students reach for acetone or acetonitrile when they want a polar aprotic environment that speeds up things like SN2 substitutions. Aprotic doesn’t just mean “won’t give up a proton”—it often nudges nucleophiles to do their best work. Acetonitrile boils hot enough for tough jobs but lets you strip things away in the rotovap like a dream.
Some folks look at solvents as just a medium, but the physical traits—boiling point, odor, viscosity—matter as much as anything. Toluene or xylene sees a lot of use in big-scale reactions because they hold up at higher temperatures and don’t vanish like diethyl ether. If you’re doing work-up, water-miscible solvents can be a blessing since you can just pour into your aqueous wash and things separate cleanly.
Lab safety can never fall out of view. I remember an old postdoc pointing out how people keep using hexane for column chromatography because it's cheap and works well—but it’s neurotoxic and far from green. Ethyl acetate, on the flip side, has lower toxicity, gets the job done for plenty of extractions, and doesn’t cling to glassware the same way.
Green chemistry’s buzz isn’t just lip service. Garbage disposal bills and stricter regulations make people look at alternatives to old petrochemical staples. Water, supercritical CO2, or bio-based solvents like 2-methyltetrahydrofuran cropped up thanks to these pushes—less harm for the chemist, less cleanup after. Finding a water-compatible catalyst or adjusting a process for greener options sometimes saves more than just money: it keeps stuff out of your lungs and local waterways.
Not every reaction welcomes water. Peptide couplings, lithium aluminum hydride reductions, alkyl lithium additions—just a whiff of moisture derails things. Drying solvents becomes routine: I still remember spending half a day swapping molecular sieves for old-school sodium/benzophenone distillation, just to get dry THF. Gloveboxes and Schlenk lines protect your mixtures. Quality suffers fast once careless solvent storage creeps in.
If you only listen to dogma, you risk missing improvements in the field. News alerts—like new ways to recycle ether, or tandem solvent/catalyst combos—mean that what was gospel last year can shift overnight. Keeping up doesn’t just show respect for the job; it’s required to keep up with costs, safety, and new science. Every bottle in the stockroom stands in for years of trial, error, and sometimes, a little bit of luck.
| Names | |
| Preferred IUPAC name | 4-{[(1R,5S)-5-propyloxan-2-yl]oxy}phenyl trifluoromethanesulfonate |
| Other names |
4-(trans-5-Propyl-tetrahydro-2H-pyran-2-yl)phenyl trifluoromethanesulfonate 4-(Trans-5-Propyl-tetrahydropyran-2-yl)phenyl triflate |
| Pronunciation | /traɪˌfluːərˌmɛˈθeɪnsʌlˈfɒnɪk ˈæsɪd fɔːr træns faɪv ˈprəʊpɪl tɛtrəˌhaɪdrəˈpɪrən tuː aɪl ˈfiːnyl ˈɛstər/ |
| Identifiers | |
| CAS Number | 1428666-93-8 |
| 3D model (JSmol) | `C1CC(CC2=CC=C(OS(=O)(=O)C(F)(F)F)C=C2OC1)CCC` |
| Beilstein Reference | 2591097 |
| ChEBI | CHEBI:17995 |
| ChEMBL | CHEMBL4169156 |
| ChemSpider | 31974128 |
| DrugBank | DB08484 |
| ECHA InfoCard | 100_1768_120 |
| EC Number | EC 684-125-1 |
| Gmelin Reference | Gmelin59192 |
| KEGG | C21004 |
| MeSH | D017265 |
| PubChem CID | 25180946 |
| RTECS number | WN5151000 |
| UNII | 3Y3BL9T6YW |
| UN number | Not assigned |
| Properties | |
| Chemical formula | C16H21F3O4S |
| Molar mass | 418.41 g/mol |
| Appearance | White solid |
| Odor | Odorless |
| Density | 1.28 g/cm3 |
| Solubility in water | insoluble |
| log P | 3.6 |
| Acidity (pKa) | -7.6 |
| Basicity (pKb) | -6.3 |
| Magnetic susceptibility (χ) | -86.98 × 10⁻⁶ cm³/mol |
| Refractive index (nD) | 1.485 |
| Viscosity | 218.0 mPa.s at 20 °C |
| Dipole moment | 3.0476 D |
| Thermochemistry | |
| Std molar entropy (S⦵298) | 528.8 J·mol⁻¹·K⁻¹ |
| Pharmacology | |
| ATC code | This product does not have an ATC code. |
| Hazards | |
| Main hazards | Causes severe skin burns and eye damage. Causes serious eye damage. |
| GHS labelling | GHS02, GHS05, GHS07 |
| Pictograms | GHS05 |
| Signal word | Danger |
| Hazard statements | H314: Causes severe skin burns and eye damage. |
| Precautionary statements | P261, P264, P271, P273, P280, P301+P312, P302+P352, P305+P351+P338, P312, P330, P337+P313, P362+P364 |
| NFPA 704 (fire diamond) | 3-0-2-Acид |
| Flash point | > 172.0 °C |
| REL (Recommended) | 10 mg/m3 |
| IDLH (Immediate danger) | Not Established |
| Related compounds | |
| Related compounds |
Trifluoromethanesulfonic acid 4-(Trans-5-Propyl-tetrahydropyran-2-yl)phenol Phenyl trifluoromethanesulfonate 4-Substituted phenyl triflates Aryl triflates Tetrahydropyranyl derivatives |
