- When the solids need to be removed by filtration, but the suction filtration is particularly slow and basically unable to pump, consider using a centrifuge.
- When doing the reaction, the speed of the stirrer should be well controlled so that the liquid in the system should not splash on the bottle wall during stirring. Liquid splashing means that droplets are leaving the system.
An example may be better understood: I want to do a low-temperature reaction in an ice bath, but a drop of liquid splashes on the wall of the bottle, then this drop of liquid is actually at room temperature before it flows back into the system, and side reactions may occur. Up.
- When the reaction always fails, you can suspect the problem of the raw materials. Sometimes the domestic solvent is re-evaporated and the reaction is successful. Sometimes it is because the water content in the solvent is too high.
- When using a pressure-resistant bottle for heating reaction, do not think that it will not fry after heating for a long time and the system is completely stable. Be careful. I saw it myself. I started heating the pressure bottle overnight at night. Nothing happened in the middle of the night. It exploded at noon the next day. After the explosion, the glass of the fume hood baffle was completely shattered. My personal advice is that as long as there is a fume hood with a pressure bottle in operation, there must be no one nearby doing experiments, and the fume hood should be kept closed. When you need to stop heating, just pull the fume hood a little bit open, reach in and turn off the heating, then close the fume hood, and then use it normally after the system has completely cooled down. And do not use the cracked pressure bottle, do not die.
- If you are not in a hurry, don’t react on rainy days. Humidity in the air may affect the reaction. In addition, don’t think that the protective gas is omnipotent. There is a possibility that the water content in the nitrogen is too high to affect the reaction, although I have never seen this in China. But if the reaction cannot be made, and the reason is really not found, let’s see if it is caused by this factor. A foreign example is to change nitrogen to argon. The argon that can be used in this place is even drier, and then the reaction is complete.
- Water pump + tube + adapter + flask can replace the vacuum drying box to a certain extent. Of course, it would be better to have a vacuum drying oven. Develop the habit of drying your products at will. Long-term drying can help avoid various solvent peaks on the spectrum, and can help you more accurately figure out how many products you have, and other advantages.
- When you want to spin off the solvent to get a solid, if you spin to dry, the solid will stick to the wall of the flask and it will be difficult to scrape. You can consider not to spin dry thoroughly during rotary steaming, leaving a small amount of solution, use a dropper to suck out and choose to dry naturally, or add it to a bad solvent and filter after the solid has separated out, which can save you from the pain of scraping the wall of the flask with a medicine spoon. .
- You can wear two pairs of gloves when doing experiments for better protection. If it gets dirty, just throw away the outer gloves. Don’t be stingy when it comes to protecting your health.
- When drying, try to use sodium sulfate instead of magnesium sulfate. Except that magnesium ions sometimes damage the product due to coordination problems, it is faster to filter with sodium sulfate when filtering. Although it seems that the water absorption effect of magnesium sulfate is better. .
- Wear the lab coat well, in addition to preventing accidentally breaking things and scratching the arm, it can also reduce the skin’s absorption of volatile substances. Wear a good mask to prevent silica gel and dust. When you enter the laboratory, you must wear goggles, which is more important than lab coats and masks.
- Before doing the experiment, check the MSDS of each reagent you need to understand the toxicity of the reagent you use, and the fire extinguishing measures in case of fire (use dry powder or carbon dioxide fire extinguisher, etc.). On the MSDS, there is information about GHS hazard statements. This information is very important and allows you to notice a lot of the key operating points of the reagents you use. For example, pyridine is particularly flammable, benzoyl chloride is highly sensitizing, and so on, can make you notice many dangers that you would not notice. At that time, I checked the MSDS before using benzoyl chloride. I knew that this guy is extremely allergenic. Practice shows that I wear a lab coat and gloves. Even the gas he emits makes my wrists itchy. If I hadn’t checked the MSDS, I wouldn’t know where the hand itch came from.
To vomit, most of us only know that butyl lithium is easy to burn, but in fact, butyl lithium has a variety of strange artifacts, such as reproductive toxicity, causing organ failure, and the like, and acetic anhydride. I remember “inhalation may be fatal.” “. Many reagents actually have properties that are completely unnoticeable at ordinary times.
- When washing the organic phase in the separatory funnel, wash it with saturated brine. The two-phase separation will look better. After all, the ion content is higher and the polarity is stronger. It is relatively easy to emulsify with distilled water. But it depends on the specific experiment, not to tell you not to wash with distilled water…
- Develop the habit of recrystallizing solids easily, and sometimes there will be unexpected surprises. For example, the separation of cis and trans isomers.
For the cis and trans isomers of the same solid substance, the difference in polarity is so small that the column cannot be separated. However, during recrystallization, it is possible that isomer A has a lower solubility than isomer B, and will preemptively precipitate, and in the presence of crystal nuclei Next, isomer A is further precipitated, so that it is possible to obtain isomer A directly. But in this case, it is not easy to get pure isomer B…
As long as the experiment is over at night and I get off work, if there are solids that have not been purified, I habitually set up a recrystallization before leaving, and wait for the next day to see if I can pick up a big deal.
- For compound characterization, hydrogen spectrum, carbon spectrum, high resolution, single crystal XRD, element analysis are commonly used. Among them, elemental analysis can be said to be a notorious thing, and the purity required by the hydrogen spectrum and carbon spectrum is significantly lower than that of elemental analysis. Generally speaking, when the compound is very clean on NMR, you will have the guts to challenge elemental analysis.
In addition to the purity of the compound, the most common cause that affects the results of elemental analysis is that the solid contains dust. Before sending the sample for elemental analysis, remember to pass the sample through a microporous membrane; otherwise, make sure that the compound is completely dry.
Pay special attention to single crystals. Single crystals are not necessarily a good thing for elemental analysis, because solvent molecules may be wrapped in single crystals, which results in errors in elemental analysis. In order to avoid this situation, before sending the sample for element analysis, the sample should be checked by NMR. Don’t assume that the sample before the dust filter is clean by NMR, and the dried sample after the filter must not contain solvent.
- Methanol can dissolve silica gel. If methanol is used in the mobile phase when passing through the column, 80% of your product will contain silica gel dissolved in methanol after being spin-dried. Use a solvent such as methylene chloride to re-dissolve what you get, and then Just pass the microporous membrane and remove the silica gel.
The same thing, pay attention to the sand core funnel. If you use the sand core funnel to filter out the solids, when you want to scrape the product from the funnel, you will probably scrape off the sand core together. Remember to also use the microporous filter membrane.
- In the long-term reflux reaction, in addition to using vacuum ester to completely seal the system, pay attention to the flow rate of the protective gas. Do not open the nitrogen/argon gas too much, because in this kind of closed system, this kind of protective gas is actually adding extra pressure to the system. In case your system is not well sealed in any part of the system, the flow rate is so large. Shielding gas will “squeeze” the solvent in your system back into that gap, so the solvent in your system will run very fast. I have tried the reaction at 80 degrees, with water as a solvent, which dries the water alive.
- There are many methods for low temperature. In addition to ice water bath and low temperature reactor, you can consider using liquid nitrogen or adding dry ice to acetone. However, a special container is required, and general glass is not enough. It seems to be called Dewar?
- After the product is finished, don’t use all of it in the next reaction, save a little bit, and use it to monitor the reaction.
- If your expected product is solid, but what comes out is liquid, it does not mean that your product is wrong. Sometimes we just need a little weird method and procedure to let the solid out. There are many strange methods. The ones I have tried are: directly throw out in the refrigerator to precipitate; add a poor solvent to the refrigerator for a few hours or overnight and then precipitate; add a poor solvent and leave it at room temperature for one hour and then precipitate; and so on. Everything has happened. I just want to remind you not to lose anything, especially if the NMR is correct.
- After the product is made, you can add some silica gel with a sand core funnel after liquid separation, and wash the product again to remove impurities.
The solid product after the column is not necessarily pure, it can be recrystallized easily.
- Pointing the board is an important basis for passing the pillar, but the board and the pillar may vary at any time. In addition to my own practical experience, I looked at the experimental part of other people’s literature, clicked the board and pointed out cyclohexane: ethyl acetate 8:2, and the column turned into cyclohexane: ethyl acetate 95:5. In other words, sometimes when you cross the pillar, you need to be more cautious than pointing the board.
- Don’t completely believe in the results of spotting, especially when you are trying to spot ionic compounds… Although generally two spots are indeed two substances. Sometimes your matter is pure, but the possibility of decomposing on the board is also completely present.
- If your product can’t run in petroleum ether at all when you tap the board, you can consider using petroleum ether to punch hard to remove other impurities after loading the column. Sometimes the ionic compound can be run with a normal silica gel column, and sometimes this can be washed away with dichloromethane, and then a little methanol is added to the mobile phase to flush the product down to purify your things.
- The literature sometimes uses special substances for a reason. It is best to clarify the motivation of people using certain reagents. I once tried an ion exchange column. The literature used ammonium bicarbonate, but the laboratory didn’t. I checked various principles and adsorption strength, and found that sodium bicarbonate solution can completely replace ammonium bicarbonate solution, so I used sodium bicarbonate without authorization. I didn’t know that the instructor told me during the group meeting that there is a difference between the two. The difference is that ammonium bicarbonate can be removed by rotary evaporation.
- Generally, static electricity is easily generated when experimenting with gloves. This will cause the problem of random flying of solid powders, and it will also affect your balance-take the glass bottle with gloves and put it on the balance with five decimal places to try it out. The value will not stabilize for a long time. Sometimes you need to take off your gloves to handle solids, or you can consider buying some kind of anti-static device.
- The relevant knowledge of inorganic chemistry can be used in organic post-processing. For example, some stannous chloride reduction reactions are not so easy to wash with water, such as the reaction of aniline to phenylhydrazine hydrochloride. The product is likely to contain a lot of stannous chloride, but NMR can’t tell it. This is in the literature. There are reports (I still remember that article was directly based on the preparation process published by another person is not pure preparation at all). In some cases, you can consider washing with ether. Stannous chloride is soluble in ether. There are other applications that use methanol recrystallization to remove copper salts. I can’t remember the details, but don’t ignore the usefulness of some inorganic knowledge in organic experiments.