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Digging into the backstory of 6-Chloro-1-hydroxybenzotriazole, many experts remember the 1990s as a hotbed for new peptide coupling additives. Research groups facing impurities and safety concerns in classical benzotriazole-based reagents steered attention toward halogen-substituted derivatives. Over time, 6-Cl-HOBt edged into the spotlight for its improved reactivity and safer profile over its parent compound HOBt. The shift reflected years of troubleshooting and collaboration between academic labs and manufacturers who wanted something better than the risky dry HOBt often used before. Pharmaceutical innovators, especially those focusing on modern peptide therapeutics, have relied on this compound for more consistent results since its debut, cementing its role in synthesis labs worldwide.
6-Cl-HOBt, a white to off-white crystalline powder, grocers up as a stabilizer and activator in peptide coupling chemistry, plugging major gaps in selectivity and yield that often plague standard reactions. Labs focused on GMP manufacturing recognize its value during process-scale up, especially thanks to its reduced tendency to form explosive peroxides. The product’s niche comes into sharper relief in the context of pharmaceutical and biotech synthesis, where alternatives often risk more side reactions or less manageable safety profiles. Consistent batch-to-batch performance keeps it a staple for any operation focused on regulatory compliance and reliable results.
With a molecular formula of C6H4ClN3O and a molecular weight close to 169.57 g/mol, 6-Cl-HOBt presents as a solid, usually stable at room temperature. It has moderate solubility in organic solvents like DMF, DMSO, and acetonitrile, and it resists rapid degradation under dry conditions. Its melting point runs around 150–152°C, which not only fits common process windows but also keeps handling straightforward. Halogen substitution on the benzotriazole ring lowers the material’s sensitivity to friction and heat, cutting down on hazards tied to similar coupling agents.
For pharma-grade batches, purity levels typically land above 98.5%, confirmed by HPLC and supported by detailed COAs listing residual solvents, heavy metals, and water content (usually less than 0.5%). Labels on pharma-grade containers always go beyond just the name and batch: they log storage temperature ranges (usually 2–8°C), expiration dates, and lot tracing info, which keeps users and regulators on the same page. Every shipment tags along with documentation like an MSDS, aligning with expectations from regulatory authorities in regions covered by BP, EP, and USP guidelines.
Synthesizing 6-Cl-HOBt often kicks off from 6-chlorobenzotriazole parent material, reacting under controlled temperature in an oxidizing medium. Experienced chemists will vouch for careful control over the chlorination step, which prevents off-target halogenation. Common routes take advantage of sodium nitrite and hydrochloric acid to set the initial stage, followed by steps under mild, anhydrous conditions to install the hydroxyl group cleanly at position 1. Multiple recrystallizations strip away colored and inert byproducts, guaranteeing high purity. Given the hazards lurking in uncontrolled benzotriazole chemistry, many process teams place heavy emphasis on closed systems, solvent recovery, and comprehensive in-process checks until the final powder clears specs.
Core to modern peptide chemistry, 6-Cl-HOBt acts as a coupling additive by stabilizing an intermediate O-acylisourea formed from carbodiimide activators, channeling the reaction directly toward the amide bond of interest while minimizing unwanted side products. Some chemists modify the triazole ring or swap out protecting groups to tweak solubility and reactivity for special-case syntheses. One notable benefit sits in the compound’s lower tendency—compared with HOBt—to undergo self-reactive decomposition that sometimes sidelines less stable triazoles. No discussion with a synthetic chemist would skirt the point that this molecule outperforms many classic coupling aids on both safety and yield grounds.
Depending on the region or supplier, 6-Chloro-1-hydroxybenzotriazole gets listed as 6-Cl-HOBt, 1-Hydroxy-6-chlorobenzotriazole, Benzotriazole, 6-chloro-1-hydroxy-, or CAS number 26198-19-6. Many catalogs drop the “hydroxy” prefix or exchange the position, but all reference the same potent reagent.
Past accidents with benzotriazole derivatives taught many in the field to handle even “improved” compounds with care. Although the chlorine substitution reduces the risk of spontaneous combustion, shipping teams always follow ADR and IATA protocols for potentially hazardous chemicals. Standard PPE—lab coats, goggles, gloves—remains mandatory, plus spill containment and disposal steps in line with local environmental rules. Many preparation areas feature explosion-proof refrigerators, grounded transfer lines, and strict logs of every gram handled. Process safety teams go further, performing regular audits and staff refresher training to avoid any slips, especially during scale-up.
Watch any peptide synthesis lab, and it’s clear why 6-Cl-HOBt matters. The challenge lies in stringing amino acids together with high efficiency, low epimerization, and minimal side products, pains that this reagent consistently addresses. It steps in for small- and large-scale pharmaceutical production—solid-phase peptide synthesis, custom oligonucleotide building, and where ever scientists need reproducible amide bonds. Biotechs increasingly trust it for investigational therapies, where purity and regulatory resilience can impact project timelines and trial approvals.
Teams mastering peptide therapeutics press forward with high-throughput screens, and each subtle improvement in yield or side product reduction can save months of work. 6-Cl-HOBt’s reliable performance supports these moonshot pursuits by giving chemists room to explore new sequences and unusual building blocks without scrapping tons of product to poor conversion rates. On the manufacturing end, consistent quality lets process chemists shave off extra purification steps, driving down cost and reducing waste.
Research teams track any molecule’s safety, and 6-Cl-HOBt holds up well compared with old-school peptide additives. Acute toxicity studies flag only moderate irritation risks to skin and eyes—nothing that can't be managed with the right lab routines—and chronic exposure studies in animal models find no red flags like genotoxicity. Hazard statements by regulatory bodies focus more on the dust and reactive intermediates than the base compound, underlining the advantages that motivated chemists to switch over decades ago.
Looking forward, advances in peptide virtualization, flow chemistry, and continuous manufacturing point to a world where coupling reagents like 6-Cl-HOBt get pushed to their limits for ever-faster, ever-cleaner drug development. Regulatory trends demand even stricter impurities tracking and lower residuals in finished APIs, so suppliers and users share the pressure to innovate further—both in purification and in handling safety. As the market for peptide and protein-based therapies booms, further tweaks to the molecule and new analogues may crop up. For now, its shelf life as a preferred coupling additive seems nowhere near ending, and the work of fine-tuning its handling, documentation, and integration into green chemistry pushes steady progress on every front.
6-Chloro-1-hydroxybenzotriazole, known as 6-Cl-HOBt, rarely gets its day in the sun. In pharmaceutical research and active pharmaceutical ingredient (API) manufacturing, this chemical quietly powers some of the most pivotal steps in peptide synthesis. A closer look reveals how it transforms routine labs into spaces for genuine discovery, not just at the bench level but when balancing safety, efficiency, and purity in ways people outside this field may never consider.
Connecting amino acids into strong, stable chains marks the foundation of peptide drugs. Without the right tools, these reactions leave open opportunities for dangerous by-products, low yields, or impurities that could spell disaster for the final medicine’s quality. 6-Cl-HOBt steps in to make these connections cleaner and more reliable by suppressing side reactions. Scientists trust it because it stands out from traditional reagents by reducing the formation of by-products, thus protecting both the worker and the patient down the line.
Pharma grade always means one thing: the highest purity. For 6-Cl-HOBt with the BP, EP, and USP monikers, this translates to strict adherence to British, European, and United States pharmacopeia guidelines. Skipping these standards is not optional. Drug makers know that impurities—even those at trace levels—can introduce risk. Authorities demand clear, repeatable evidence that every batch aligns with established purity profiles. In my years working alongside chemists, nobody risks cutting corners here. Reputations and patient outcomes ride on every milligram.
Decades back, the parent compound HOBt was the preferred choice, but it carried a reputation for safety hazards—particularly as a fire and explosion risk. That risk kept me cautious in every step, double-checking every guideline before handling. 6-Cl-HOBt offers a safer, more stable alternative, especially in dry form. Less risk of runaway reactions goes a long way in keeping labs functional and lives safe.
The world’s supply of synthetic peptides continues to expand, from diabetes to cancer treatments. Projects I’ve witnessed would not hit their timelines or cost goals without reliable coupling reagents like 6-Cl-HOBt. Its role gets even more important now with the rise of complex biologics where each link in the chain must be flawless. Drug developers face tight deadlines and tough regulatory reviews; reagents that support dependable synthesis cycles can make the difference in whether a therapy moves from trial to market.
From the manufacturing floor to regulatory agencies, dialogue around process optimization and safety keeps shifting. Chemists seeking to improve yields and cut costs without sacrificing safety value alternatives to hazardous agents. Regulators and auditors notice when companies favor updated, lower-risk reagents. To keep trust intact, open sourcing and sharing real-world data on 6-Cl-HOBt’s stability, storage, and compatibility with automated synthesis helps everyone across the chain—from scientist to supplier to patient.
Finding smarter, safer ways to craft molecular bonds won’t end with 6-Cl-HOBt. Its success illustrates the value of chemistry that enables innovation without loading the system with risk. The hard lessons of the past echo in today’s strict standards and safety-driven workplace. Building the next generation of peptides and medicines means keeping a critical eye on every reagent, every process. In the hands of today’s skilled scientists, 6-Cl-HOBt offers more than a tool—it grants peace of mind and a path forward in an industry where every detail counts.
In the world of pharmaceutical manufacturing, 6-chloro-1-hydroxybenzotriazole—known to many as 6-Cl-HOBt—plays a unique part. Used widely as a coupling agent in peptide synthesis, this compound doesn’t just pop up out of nowhere. Production standards draw clear lines, and only careful control builds real trust. Pharmaceutical-grade material isn’t about finding the cheapest raw powder. It's about hitting, and documenting, tight purity marks that protect patients and enable reproducible science.
For anyone involved in regulatory submissions or scale-up, purity stops being a line on a spec sheet and starts influencing outcomes. Pharma grade 6-Cl-HOBt—meeting BP (British Pharmacopoeia), EP (European Pharmacopoeia), and USP (United States Pharmacopeia) grades—means looking for purity levels above 98%. Sometimes, the certificate reads 99% or more, but 98% marks the accepted baseline. Those numbers aren't plucked from thin air. Impurities, particularly residual solvents or unreacted starting materials, carry real risks, ranging from allergic reactions to unpredictable side effects in end products.
Rarely does a spec stop at purity. An honest certificate covers moisture content—often valued below 0.5%—because water can degrade active peptides or trigger unwanted reactions. Melting point comes next, usually between 150 and 154 °C, which signals that the compound sits in a stable form and that storage hasn’t introduced any breakdown products. Heavy metals like lead, cadmium, and arsenic must fall far below 10 ppm; the best lots dip under 2 ppm, which many global regulators have started demanding. Chloride and sulfate levels get checked as well. A sulphate content below 0.05% shows diligence in purification, not just cutting corners with a fast filter. Loss on drying—almost a ritual in quality labs—proves the batch hasn’t taken up excess water or volatile impurities along its journey.
I've seen too many labs sidestep these details hoping to save a little upfront. Purity and specs often sound like technical jargon, until a contaminated batch ruins months of work, or worse, derails an entire project aimed at regulatory approval. Suppliers sometimes cut costs with technical or reagent grade material. The difference might look invisible, but it turns big in critical applications. In my experience, sticking to pharma grade cuts down troubleshooting time later. Every credible certificate should come with a full HPLC trace, not just a purity figure. If a manufacturer hesitates to provide detailed analyses—think FTIR, NMR, residual solvent GC-MS checks—walk away. No amount of paperwork fixes problems already shipped in a drum or a bottle.
It's on everyone—from procurement to lab staff—to recognize the risks of non-pharma material. Sourcing from audited factories ensures consistency batch after batch, especially as regulations tighten. Investing in 6-Cl-HOBt that clears BP, EP, and USP checks always seems expensive in the short run but underpins trust and repeatable results down the line. A lack of shortcuts on purity keeps finished drugs safer, research more reliable, and compliance officers off your back. Respect the numbers, scrutinize the documentation, and ask suppliers hard questions. That’s how the best labs keep their edge and protect the people relying on the science.
Anyone who’s spent time in a pharmaceutical lab learns fast—some chemicals turn dangerous without the right care. 6-Chloro-1-hydroxybenzotriazole, often called 6-Cl-Hobt, belongs to a group of compounds that demand respect. Known for its use as a coupling agent, it holds value but also brings risks. This particular substance reacts strongly with acids, bases, and reducing agents. That means a casual approach to storage creates unnecessary hazards. Based on years spent around sensitive lab stockrooms, I’ve seen the difference between a tidy, climate-controlled cabinet and a loose, stacked shelf that gets too warm. An orderly method wins every time.
Storing 6-Cl-Hobt in a tightly closed container, away from moisture, sunlight, and heat, minimizes the chance of degradation or hazardous vapor release. In my experience, it stays most stable around standard cool room temperatures, never exceeding 25°C. Some facilities use dedicated chemical fridges, marked with clear labeling. This isn’t about excess caution—high humidity or a surprise heatwave quickly ends up causing safety headaches.
Handling this material always deserves full attention. Simple nitrile gloves and splash-proof goggles offer the minimum defense. A face shield and lab coat boost protection during weighing or pouring. Dust or fumes call for working in a certified chemical fume hood—never open the container at a crowded bench. I learned the value of never skipping the fume hood after watching an unprotected colleague suffer a coughing fit from powdered residue. The right gear and careful habits keep those stories rare.
Spills tend to happen when everyone’s busy or distracted. If a small amount hits the bench, staff trained in hazardous response use inert absorbent material—fine sand or a commercially available spill kit. They sweep or scoop the debris into a sealed, labeled drum. Larger spills require air extraction systems and proactive evacuation, as outlined by workplace safety protocols. It becomes second nature to document every incident, no matter how minor.
Preparing and transferring 6-Cl-Hobt inside a fume hood is standard practice. Fume hoods pull vapors away from breathing zones and limit fire hazards. I’ve also seen success with enclosed weigh stations fitted with carbon filters; these help in environments where large volumes get measured regularly. Ventilation is one place where shortcuts catch up with people—long hours around poorly ventilated labs have led to chronic symptoms for some of my peers. Clear labeling and containment keep containers separated from incompatible materials, such as strong acids or oxidizers.
Good training gives everyone a sense of control instead of fear. Safe storage, handling, and waste removal feature in every good onboarding plan. Posters, checklists, and refresher drills reinforce safe behaviors. Working with a chemical like 6-Cl-Hobt, one person’s mistake easily affects the whole team. Emergency eyewash stations and showers sit close to busy areas, not tucked away in a corner. Calling out gaps in safety drills doesn’t annoy colleagues; it protects them.
Some labs take shortcuts to save time or space, stuffing hazardous compounds too close together. Installing modular storage with clear partitions helps reduce risk. Digital inventory systems also track shelf life and remind staff of expiration dates—no one wants forgotten stock decaying in the back corner. Ongoing conversations about safety, transparency in incident reporting, and investing in upgraded containment can turn a cycle of close calls into consistent, safe operations.
6-Chloro-1-hydroxybenzotriazole, better known in chemistry circles as 6-Cl-Hobt, finds its place during peptide coupling steps in pharmaceutical labs. It reacts quickly, making it a valued tool for many synthetic chemists. Still, once the bottle comes out of the storage cabinet, the stakes get higher. This compound carries real hazards. Even the best folks in our industry make mistakes, so no one questions the value of double-checking safety.
Before breaking the seal, eye protection should come out. Splash goggles make the difference between a hazardous splash and a routine day at work. Gloves are required, not just for 6-Cl-Hobt, but for everything labeled as potentially harmful. The usual choice runs toward nitrile gloves, because they don’t break down as quickly as latex with strong chemicals. Long sleeves, cotton lab coats, and closed shoes don’t just check the box — they prevent burns and accidental exposure far better than open cuffs or sandals ever will. Old-timers sometimes take shortcuts, but getting lucky once doesn’t mean the odds will keep falling your way.
Work involving 6-Cl-Hobt needs a fume hood. This chemical doesn’t just pose a dust risk. Its dust can irritate the lungs, and some reactions release gases nobody wants near their face. I remember a case in a student lab where someone ignored the hood, and we ended up evacuating after a coughing fit. Fume hoods exist for a reason. Keeping them uncluttered makes spills far easier to manage, too.
Some folks don’t realize how moisture-sensitive and reactive 6-Cl-Hobt can get. It’s best to keep the bottle tightly closed, away from heat, direct sunlight, and especially away from sparks or open flames. I once heard stories of bottles breaking down after being left open too long, with the material clumping and changing color—a clear signal to dispose of the batch. Never store it with acids or bases, or alongside other strong oxidizers. Keeping it above eye level on a crowded shelf is a gamble; always aim for cool, low, dry spots with clear labels.
Sometimes the worst happens. Spills need careful cleanup. Out comes the spill kit, not just paper towels. Socks and absorbent pads grab the material, and everything goes into a sealed bag, clearly labeled for hazardous waste pickup, never the building garbage. In case of skin contact, the right reaction is washing well with plenty of water, not hoping for the best. Any eye exposure calls for an eye wash—minimum fifteen minutes.
Real safety depends on people speaking up and sharing knowledge. One-time training doesn’t stick for life. Ongoing reminders, posted signs, and mentors who watch out for each other keep standards high. Lots of close calls never land in the incident log, but a quick “Hey, your gloves have a hole” or “Let’s use the shield” prevents trouble from escalating. Clear protocols and empowered workers make labs safer places to learn and work.
It’s tempting to downplay hazards, thinking routine will keep things safe. In my experience, complacency grows in silence. Transparency about process changes, near-misses, and new findings only helps the whole team. Even a small safety tweak—like switching cleaning schedules or adding a new sign—can keep risks low and minds focused on the job. This isn’t just about compliance. It’s about respect for the craft, the colleagues, and our own health. A culture of caution saves more than regulations ever could.
6-Chloro-1-Hydroxybenzotriazole — better known to specialists as 6-Cl-Hobt — might not catch the public eye, but this chemical sits at the heart of advanced peptide synthesis. It’s the kind of compound that makes a difference behind the scenes, where consistency, purity, and reliability drive the entire pharmaceutical supply chain.
People usually wonder how much to order — not just for efficiency, but for the very real frustrations of handling, storage, validation, and cost. After working on the supply side of specialty chemicals for pharmaceutical manufacturing, I've often seen engineers, lab managers, and production planners run circles trying to match their purchase size with their project demands. The options aren’t just about a “small” or “large” box; every choice carries practical, economic, and regulatory weight.
Most reliable suppliers offer sealed HDPE or aluminum containers, lined with inert films to block out moisture and oxygen. The smallest batch sizes hover around 100 grams to 500 grams, which work for development labs, early-stage research, or sensitive tests where even half a kilo could last months. These containers are sealed tight—sometimes double-bagged inside tamper-evident drums—because even brief exposure to air means contamination or loss of potency.
For teams scaling up, 1-kilogram and 5-kilogram drums become the norm. At this size, you start worrying about shelf space, batch traceability, and ease of handling, especially in busy pilot plants. These drums need robust labeling, batch numbers, and handling certifications. I’ve watched technicians wrestle with unwieldy 5-kg pails, sometimes splitting one order across multiple smaller containers to cut down on waste and reduce contamination risk. It often comes down not just to volume, but to safe, traceable access for operators who need repeatable results—and don’t want to risk an entire production run on a single, clumsy container.
Larger manufacturing runs lean on 10-kilogram or 25-kilogram fiber drums. These bulk sizes work out only if the plant processes enough batches to use the contents quickly. I’ve heard from procurement managers who regret over-ordering and winding up with expired product or fighting to maintain compliance when stability data lags behind shipment frequencies. Handling these drums requires training—not just to lift and move multiple kilograms, but also to meet GMP audit standards for cleanliness and cross-contamination control.
Regulatory rules push for tamper-evidence, serialized batch tracking, and exact documentation. The higher the grade—BP, EP, USP—the tighter the scrutiny. Auditors check not just paperwork, but also that containers remain intact and that their closures still seal after repeated access. As a consultant, I once encountered a batch quarantined for months just because someone failed to reseal a drum properly during sampling—highlighting how packaging choice becomes a risk management decision.
Split-lot packaging gives buyers the best of both worlds—several small containers in one larger order, minimizing repeated air exposure and contamination. Tamper-evident seals and serial tracking technology also help labs stay audit-ready and avoid loss of valuable material. More suppliers are stepping up transparency, providing shelf life studies and recommendations for secondary repackaging. Companies that link ordering size to real-time inventory management can cut costs, lower spoilage rates, and operate with greater confidence—knowing every gram counts in today’s pharmaceutical landscape.
| Names | |
| Pronunciation | /ˈsɪks-klɔːr-hɒbɒt/ |
| Properties | |
| Density | 1.7 g/cm3 |
| Basicity (pKb) | 5.2 |
| Hazards | |
| Signal word | Warning |
Chengguan District, Lanzhou, Gansu, China
