Preparation of N-Metlhylformamide
N-methylformamide is best made by the re- action of methylamine with formic acid. The re- iction proceeds like this:
The methylamine (a base) reacts with formic acid to form the methylamine salt of formic acid. The heat that this reaction builds up then causes this intermediate salt to lose a molecule of water and form N-methylformamide. Since water is a product of this reaction, the underground chemist wants to keep water out of his starting materials as far as is possible. That is because having less water in them will shift the equilibrium of the re- action in favor of producing more N-methylfor- mamide.
Both of the starting materials have water in them. The usual grade of formic acid is 88% pure and 12% water. It cannot be made any purer by distilling. The chemist can put up with the 12% water, but if a higher purity formic acid is avail- able, it is worth the extra cost. The usual grade of methylamine is 40% by weight in water. The majority of this water can be removed by using the apparatus shown in Figure 18. Methylamine may also be obtained as a gas in a cylinder. In that case, the methylamine can be piped directly into the formic acid.
The glassware is set up as shown in Figure 18. The 40% methylamine is in a 1000 ml round bottom flask attached to a long condenser. In the top of this condenser is a one-hole stopper. A bent piece of glass tubing is pushed all the way through this stopper so that the end of the piece of tubing extends about one or two millimeters be- low the bottom of the stopper. This bent piece of tubing then extends down through the center of the other condenser into the flask containing the formic acid. It should extend below the surface of the formic acid and end about one centimeter above the bottom of the flask containing the for- mic acid. The idea here is simple. The 40% methylamine is heated, causing methylamine gas to be boiled out along with some water vapor. These gases then travel up the condenser, where the water is condensed out, allowing nearly pure methylamine gas to be forced by pressure through the glass tubing into the formic acid.
The bent tubing has to be bent by the chemist himself from a 3-foot-long piece of glass tubing. Its outer diameter should be about 1/4 inch. The glassware is set up as shown in Figure 18 and he decides about where the tubing should be bent. If necessary, he will consult the chapter on bending glass in an Organic Chemistry lab manual. With a little practice, it is easy. A good source of flame to soften up the glass is a propane torch with the flame spreader attachment. After it is bent, he will blow through the tubing to make sure he did not melt it shut.
He is now ready to proceed. All pieces of glassware are clean and dry. Into the round bot- tom 1000 ml flask sitting on the heat source is placed 500 grams (about 500 ml) of 40% methyl- amine in water, along with 3 or 4 boiling chips. Into the other 1000 ml round bottom flask is placed 250 ml of 88% formic acid. Water flow is begun through the longer condenser. It is advan- tageous to use ice cold water in this condenser, because it will then do a better job of removing water vapor from the methylamine. A good way to get ice cold water for the condenser is to get a couple of 5-gallon pails. One of them is filled with ice cubes no bigger than a fist and topped off with water. Then the section of plastic tubing that runs to the lower water inlet of the condenser is
placed in the pail. Its end is weighted to keep it on the bottom of the pail. This pail is placed on the table along with the glassware. The other pail is placed on the floor and the plastic tubing from the upper water exit of the condenser is run to this pail. By sucking on the end of the water exit tub- ing, the ice cold water can be siphoned from the pail on the table, through the condenser, to the pail on the floor. The rate of water flow can be regulated to about one gallon per minute by put-
ting a clamp on the tubing to slow its flow. When the pail on the table is about empty, the water that has flowed to the pail on the floor is returned to the table.
The heat on the methylamine is turned on to about lA maximum. Soon the methylamine begins boiling out and moving through the tubing into the formic acid. The underground chemist checks for gas leaks in the system by sniffing for the smell of escaping methylamine. If such a leak is detected, the joint it is escaping from is tightened up.
The methylamine bubbling into the formic acid produces a cloud of white gas inside the flask containing the formic acid. It makes its way up to the condenser, then returns to the flask as a liquid. For this condenser, tap water flow is fine. The rate of methylamine boiling is adjusted so that the white gas does not escape out the top of the con- denser. As more methylamine is boiled out, a higher heat setting is required to maintain the same rate of methylamine flow.
In this process, the formic acid gets very hot. It must get hot to produce good yields of N-methyl- formamide. It sometimes gets hot enough to boil a little bit (105° C), but this is no problem. As the chemist continues bubbling methylamine into the formic acid, its volume increases until it is double its starting volume, about 500 ml. At about this time, the cloud of white gas thins and then dis- appears. This white gas is formed by the fumes of formic acid reacting with methylamine above the surface of the liquid formic acid. It disappears be- cause there is no longer much formic acid left. The chemist now begins checking to see if the re- action is complete. He pulls out one of the stop- pers from the 3-necked flask that contains the N- methylformamide and sniffs the escaping fumes for the odor of methylamine. He does this peri- odically until he smells methylamine. Once he smells it, he turns off the heat on the methyl- amine. When the methylamine stops bubbling into the N-methylformamide, he immediately lowers the level of the 3-necked flask so that the bent glass tubing is above the surface of the N-
methylformamide. This is done because, as the methylamine cools, it will contract and create a vacuum which would suck the N-methylforma- mide over into the other flask in a flash, ruining his work.
Both flasks are allowed to cool down. The methylamine is almost gone, so it can be poured down the drain. The next step is to fractionally distill the N-methylformamide. The glass-packed claisen adapter is used as the fractionating col- umn. The glassware is set up as shown in Figure 13, back in Chapter Three. The distilling flask is a 1000 ml round bottom flask with 5 boiling chips in it. The collecting flask is a 250 ml round bot- tom flask. Unlike the distillation of phenylace- tone, in this case the distillation is done under a vacuum from the beginning. The ice water siphoning system is used for the condenser, be- cause N-methylformamide has a very high latent heat of vaporization, and, without this precaution, it may collect very hot in the collecting flask.
The underground chemist is now ready to distill the N-methylformamide. All of the crude product is put in the 1000 ml round bottom flask. It will fill it about half full. The vacuum is applied at full strength, and the heat source is turned on to '/3 to lA maximum. The water in the mixture begins distilling. The temperature shown on the ther- mometer will show a steady climb during the process.
In a while, the temperature rises high enough that the chemist can begin collecting the distilled liquid as suspected N-methylformamide. If he is using an aspirator, he begins collecting in a clean, dry 250 ml round bottom flask when the tem- perature reaches 95-100° C. If he is using a good vacuum pump, he begins saving the distilled ma- terial at about 85° C. As the N-methylformamide distills, the temperature rises a little bit above the temperature at which he first began collecting the N-methylformamide, then holds steady. This temperature is noted. Distilling is continued until he has collected 100 ml. Then the heat is turned off. When the boiling stops, the vacuum hose is disconnected from the glassware.
During the distillation process, a fair amount of methylamine was lost, leaving the N-methylfor- mamide with too much formic acid. The next step is to correct this problem.
The 100 ml of N-methylformamide that has been distilled is poured back in the distilling flask with the undistilled material. The distilled mate- rial is clear, while the undistilled material has turned yellow from the heat of distilling. The glassware is set up again as shown in Figure 18. This time, the round bottom flask holding the methylamine is a 500 ml flask. It has 100 ml of fresh 40% methylamine in water in it. The bent glass tubing leads into the flask containing the N- methylformamide. This flask does not need to have a condenser on it.
The heat is turned on the methylamine and the flow of ice water through its condenser is begun. Soon the methylamine gas is bubbling into the N- methylformamide, reacting with the excess for- mic acid in it. Within about 10 seconds, the odor of methylamine can be detected above the N- methylformamide. The heat is turned off, and when the bubbling stops, the level of the N-me- thylformamide is lowered so that it is not sucked into the other flask. Once the methylamine has cooled off, it can be poured back in with the good methylamine, because it is not exhausted. Once a bottle of methylamine has been opened, it should be reclosed tightly and the cap sealed with vinyl electrical tape in order to hold in the methylamine gas.
Now the N-methylformamide is to be distilled again. The glassware is set up again for fractional distillation as shown in Figure 13. The distilling flask is a 500 ml round bottom flask, while the collecting flask is 250 ml. All pieces are clean and dry.
The N-methylformamide is placed inside the distilling flask with 5 boiling chips. (Fresh chips are used every time.) The vacuum is reapplied and the heat is turned on again to 1/3 to 1/2 maxi- mum. A little bit of water is again distilled. The temperature shown on the thermometer climbs as before. When it reaches a temperature 7° C below the temperature at which it leveled off the first
time around, the chemist begins collecting in a clean dry 250 ml flask. The distilling continues until it has almost all distilled over. About 10 or 15 ml is left in the distilling flask. If he is using an aspirator, the chemist makes sure that no water is backing into the product from the vacuum line. The yield is about 250 ml N-methylformamide. If he gets a little more, it won't all fit in the 250 ml collecting flask. If that happens, he pours what has collected into a clean dry Erlenmeyer flask and continues distilling. N-methylformamide is a clear liquid with no odor.
The N-methylformamide the underground chemist has just made is perfect for the Leuckardt-Wallach reaction. Because he began collecting it 7° below the leveling off tempera- ture, it contains a mixture of N-methylformamide, formic acid and methylamine. To get good re- sults, he uses it within a few hours after distilling it.
References
Journal of the American Chemical Society, Vol- ume 53, page 1879 (1931).
