G.Patton
Expert
- Joined
- Jul 5, 2021
- Messages
- 2,638
- Solutions
- 3
- Reaction score
- 2,708
- Points
- 113
- Deals
- 1
Introduction
In this topic, you can find chemical properties and synthesis pathway of Methaqualone (Quaalude; 2-Methyl-3-(2-methylphenyl)-4(3H)-quinazolinone) from isatoic anhydride and o-toluidine with high yield. These precursor substances are quite common and do not attract a lot of attention. You can easily buy them in a chemistry store at a good price. These methods are elementary and can be easily scaled up. Don't forget about safety and use PPE.
Equipment and glassware:
- Pear-shaped flask 10-50 ml and 100 ml;
- Buchner flask and funnel (or small Schott filter);
- Heated magnetic stirrer;
- Reflux condenser (small);
- Retort stand and clamp for securing apparatus;
- Laboratory scale (0.01 — 100 g is suitable);
- Pasteur pipette's;
- Water and oil bath;
- Laboratory grade thermometer;
- Vacuum desiccator (optional);
- Water-jet aspirator (optional);
- Beakers 100 ml x2; 50 ml x2; 10 ml x2;
- Glass rod;
- Boiling stones;
- Conventional funnel;
- Filter paper.
Reagents:
- o-Toluidine 1.1 g, 0.01 mol;
- Isatoic anhydride 1.6 g, 0.01 mole;
- Diethyl ether (Et2O) or acetone and distilled water ~50 ml;
- Dichloromethane (CH2Cl2) 100 ml;
- Petroleum ether 100 ml;
- Acetylacetone 0.39 g, 0.0025 mole;
- Ethanol (EtOH) 95% 30 ml;
- Hydrochloric acid conc. (HCl) ~10 ml;
- Methanole MeOH 50 ml;
- Acetone 50 ml.
Soluble in ethanol and ether. Insoluble in H2O;
Boiling Point: 406.9 °C at 760 mm Hg;
Melting Point freebase: 113-115 ̊C;
Melting point HCI salt: 235-237 ̊C;
Molecular Weight: 250.301 g/mole;
Density: 1.16 g/cm3 (20 °C);
CAS Number: 72-44-6.
Procedure
2,2'-dimethylbenzanilide (1)
A mixture of isatoic anhydride (1.6 g, 0.01 mole) and o-toluidine (1.1 g, 0,01 mol) is heated in a pear-shaped flask (10-50 ml) to 120 °С for 2 hours with a small reflux condenser in an oil bath. The reaction mixture after cooling is triturated with ether (or dissolve the brown mixture in warm acetone and add water to crash out the crystals). The resulting solid is collected by suction filtration on Buchner funnel (or small Schott filter) and recrystallized from a 50:50 mixture of dichloromethane and petroleum ether to give the intermediate aminoamide (2,2'-dimethylbenzanilide) (1): yield: 1.7 g (75%); m.p. 110 °C.
A mixture of isatoic anhydride (1.6 g, 0.01 mole) and o-toluidine (1.1 g, 0,01 mol) is heated in a pear-shaped flask (10-50 ml) to 120 °С for 2 hours with a small reflux condenser in an oil bath. The reaction mixture after cooling is triturated with ether (or dissolve the brown mixture in warm acetone and add water to crash out the crystals). The resulting solid is collected by suction filtration on Buchner funnel (or small Schott filter) and recrystallized from a 50:50 mixture of dichloromethane and petroleum ether to give the intermediate aminoamide (2,2'-dimethylbenzanilide) (1): yield: 1.7 g (75%); m.p. 110 °C.
2-Methyl-3-(2-methylphenyl)-4(3H)-quinazolinone (2)
A mixture of 2,2'-dimethylbenzanilide (0.5 g, 0.0025 mole), acetylacetone (0.39 g, 0.0025 mol) in ethanol (30 ml) containing a few drops of concentrated hydrochloric acid is refluxed for 1 h in a pear-shaped flask 100 ml. On cooling the title compound separated by filtration as the hydrochloride salt: yield: 0.59 g, (85%), m.p. 235-237 °C.
A mixture of 2,2'-dimethylbenzanilide (0.5 g, 0.0025 mole), acetylacetone (0.39 g, 0.0025 mol) in ethanol (30 ml) containing a few drops of concentrated hydrochloric acid is refluxed for 1 h in a pear-shaped flask 100 ml. On cooling the title compound separated by filtration as the hydrochloride salt: yield: 0.59 g, (85%), m.p. 235-237 °C.
Purification
Now begins the purification process. Put the crystals in a beaker and add roughly twice the volume of acetone, toss in a few boiling stones. They help the boil start faster and stay under control. The crystals will not dissolve, but the left over nasty-purple-stuff will. Filter the crystals and dry. If, after drying, there is a purple tint to the crystals, then recrystallize from methanol. To accomplish this, put the crystals in a small beaker add just enough MeOH to get them wet and start heating the mix. Some crystals will dissolve immediately, if they don't all dissolve bring the MeOH to a boil and add MeOH a little at a time, maintaining boiling until they have all dissolved. Now continue the boil until about 20% of the MeOH has been evaporated. Allow the solution to cool and wait. After about an hour there will be crystals forming and clinging to the sides of the tube, wait until you're sure all the crystals have formed and filter. Use acetone to wash the crystals out of your flask and to rinse as much of the nasty-purple-stuff from the crystals in your filter paper. Save both the solution and the crystals.
The recrystallization will help some, but will not purify the crystals. What has happened is that during the reaction, the nasty-purple-stuff has wrapped itself around and within the crystalline structure of the methaqualone and recrystallization will create a new surface, so an acetone wash will be able to get the rest. Now repeat the acetone boil described above, and filter and dry. You should have light steel gray to white powder, if you do, stop and put this batch aside, if you don't, do another acetone wash.
Remember the solution you saved from the recrystallization above? This is nasty-purple-stuff, MeOH, acetone and methaqualone. Put a few boiling stones in the solution and boil away half the volume. Let this set and cool, and more methaqualone will precipitate out. This can be purified with acetone as above and the result added to your completed batch. You can repeat this process until almost all the methaqualone has been recovered from the solution, but each recovery will be less pure. If you choose to do this, combine all the recovered product and do one last acetone boil to clean it up.
The recrystallization will help some, but will not purify the crystals. What has happened is that during the reaction, the nasty-purple-stuff has wrapped itself around and within the crystalline structure of the methaqualone and recrystallization will create a new surface, so an acetone wash will be able to get the rest. Now repeat the acetone boil described above, and filter and dry. You should have light steel gray to white powder, if you do, stop and put this batch aside, if you don't, do another acetone wash.
Remember the solution you saved from the recrystallization above? This is nasty-purple-stuff, MeOH, acetone and methaqualone. Put a few boiling stones in the solution and boil away half the volume. Let this set and cool, and more methaqualone will precipitate out. This can be purified with acetone as above and the result added to your completed batch. You can repeat this process until almost all the methaqualone has been recovered from the solution, but each recovery will be less pure. If you choose to do this, combine all the recovered product and do one last acetone boil to clean it up.
Last edited: