Organic Syntheses, CV 7, 438
TOSYLHYDRAZONE SALT PYROLYSES: PHENYLDIAZOMETHANES
[Benzenes, diazomethyl-]
Submitted by Xavier Creary
1
Checked by Weyton W. Tam, Kim F. Albizati, and Robert V. Stevens.
1. Procedure
Caution! Diazo compounds are presumed to be highly toxic and potentially explosive. All manipulations should be carried out in a hood. Although in numerous preparations we have never observed an explosion, all pyrolyses and distillations should routinely be carried out behind a safety shield.
A.
Benzaldehyde tosylhydrazone. A
14.6-g sample (0.078 mol) of p-toluenesulfonylhydrazide (Note
1) was placed in a
125-mL Erlenmeyer flask and
25 mL of absolute methanol was added. The slurry was swirled as
7.50 g (0.071 mol) of freshly distilled benzaldehyde was added rapidly. A mildly exothermic reaction ensued and the
p-toluenesulfonylhydrazide dissolved. Within a few minutes, the tosylhydrazone began to crystallize. After 15 min the mixture was cooled in an
ice bath. The product was collected on a
Büchner funnel, washed with a small amount of cold
methanol, and dried under an aspirator vacuum. The dry
benzaldehyde tosylhydrazone, mp
124–125°C, weighed
16.97–18.19 g (
87–93%) and was not purified further.
B.
Phenyldiazomethane (Vacuum pyrolysis method). In a
200-mL, single-necked, round-bottomed flask is placed
13.71 g (0.05 mol) of benzaldehyde tosylhydrazone. A
1.0 M solution (51 mL) of sodium methoxide in methanol (0.051 mol) (Note
2) is added via syringe and the mixture is swirled until dissolution is complete (Note
3). The
methanol is then removed by a
rotary evaporator. The last traces of
methanol are removed by evacuation of the flask at 0.1 mm for 2 hr. The solid tosylhydrazone salt is broken up with a
spatula and the flask is fitted with a
vacuum take-off adapter and a
50-mL receiver flask. The system is evacuated at 0.1 mm and the receiver flask is cooled in a
dry ice–acetone bath to about −50°C. The flask containing the salt is immersed in an
oil bath and the temperature is raised to 90°C. (We recommend the use of a safety shield.) At this temperature, red
phenyldiazomethane first begins to collect in the receiver flask. The temperature is raised to 220°C over a 1-hr period (Note
4). During this time red
phenyldiazomethane collects in the receiver flask (Note
5). The pressure increases to 0.35 mm over the course of the pyrolysis. On completion of the pyrolysis the pressure drops to less than 0.1 mm.
The apparatus is disconnected and the 50-mL receiver flask that contains the crude
phenyldiazomethane is fitted with a
water-cooled short-path distillation head and a receiver flask cooled to about −50°C in a dry ice–acetone bath. The pressure is lowered to 1.5 mm and a trace of
methanol collects in the receiver. A new receiver flask is connected and cooled to −50°C and the pressure is lowered to less than 0.2 mm. Red
phenyldiazomethane distills below room temperature (Note
6). The yield of
phenyldiazomethane, which is a liquid above −30°C, is
4.50–4.70 g (
76–80%). The product should be used immediately or stored at a low temperature (−20 to −80°C) under
nitrogen or
argon (Note
7),(Note
8),(Note
9),(Note
10),(Note
11); it is explosive at room temperature.
2. Notes
4. When carried out on a small scale, pyrolysis is complete at lower temperatures (160–200°C).
5.
Phenyldiazomethane solidifies at dry ice temperature. Care must be taken not to plug the vacuum take-off adapter; this occurs if the temperature of the receiver flask is too low. The receiver bath was maintained manually at about −50°C by addition of small pieces of dry ice to an acetone bath. We prefer to use this procedure rather than a
chloroform–dry ice bath, which freezes at −63°C, because of the toxic nature of
chloroform and the disposal problems associated with this solvent.
6. Slight warming with an oil bath at 30°C allows distillation to proceed at a reasonable rate. The bath should not be heated above this temperature. Gutsche and Jason
2 report a boiling point of
37–41°C at 1.5 mm. Although we have never experienced any difficulty in numerous distillations, Gutsche and Jason
2 report that
phenyldiazomethane "sometimes detonated violently during purification" by distillation. Therefore, we emphatically recommend that distillation be carried out below room temperature, behind a safety shield. On completion of the distillation, only a small amount of nonvolatile residue remained.
7. The checkers reported that a sample that was allowed to stand at room temperature for approximately 1 hr and then exposed to air decomposed violently after 5 min. In numerous preparations, when distilled
phenyldiazomethane was immediately stored at −20°C or at −80°C under
nitrogen, we never experienced any difficulty. We emphasize the need to keep
phenyldiazomethane cold, and under
nitrogen.
8. In runs on smaller scales, yields ranged from
84 to 91%.
9. The IR spectrum (CCl
4) shows an intense band at 4.83 μm (2060 cm
−1);
1H NMR (CCl
4) δ: 4.79 (s, 1 H), 6.7–7.6 (m, 5 H).
10.
Phenyldiazomethane shows no appreciable change on storage at −80°C for 3 months. Storage at −20°C led to significant decomposition after 2 weeks.
11. Traces of diazo compounds should be destroyed by addition to
acetic acid.
3. Discussion
Diazo compounds have previously been prepared by a variety of methods. Some of these methods include hydrazone oxidations,
3 the reaction of
diazomethane with acid chlorides,
4 the reaction of activated methylene compounds with
tosyl azide,
5 decomposition of
N-nitroso compounds,
6 diazotization of amines,
7 and pyrolysis of tosylhydrazone salts.
8,9,10,11,12,13 The present procedure for the preparation of
phenyldiazomethane illustrates the vacuum pyrolysis method introduced by Shechter
12 for carrying out the Bamford–Stevens reaction.
9
The present procedure uses
sodium methoxide in
methanol for generation of the tosylhydrazone salt. This procedure gives the highest reported yield and, unlike other procedures, also gives pure diazo compounds free from solvents. This vacuum pyrolysis method appears applicable to the formation of relatively volatile aryldiazomethanes from aromatic aldehydes. Table I gives yields of diazo compounds produced by this vacuum pyrolysis method. The yields have not been optimized. The relatively volatile diazo esters,
ethyl α-diazopropionate18 and
ethyl α-diazobutyrate, can also be prepared by this method.
TABLE I
FORMATION OF DIAZO COMPOUNDS BY VACUUM PYROLYSIS OF SODIUM SALTS OF TOSYLHYDRAZONES
|
Tosylhydrazone |
Product |
Yield (%) |
|
p-MeC6H4CHNNHTs |
p-MeC6H4CHN2 |
52 |
m-MeC6H4CHNNHTs |
m-MeC6H4CHN2 |
55 |
|
|
69 |
p-FC6H4CHNNHTs |
p-FC6H4CHN2 |
69 |
m-FC6H4CHNNHTs |
m-FC6H4CHN2 |
59 |
|
|
87 |
|
|
65 |
|
The major limitation of the vacuum pyrolysis method appears to be thermal decomposition of less volatile diazo compounds during the pyrolysis. The vacuum pyrolysis method was unsuccessful for the preparation of
1-naphthyldiazomethane and
3,5-dichlorophenyldiazomethane. However, such diazo compounds could be prepared from the corresponding tosylhydrazone salts by pyrolysis in
ethylene glycol and extraction of the aryldiazomethane into
hexane or
ether. This procedure, as described by Goh,
19 permits the periodic extraction of the potentially labile diazo compound into an organic solvent while leaving the unreacted tosylhydrazone salt dissolved in the immiscible
ethylene glycol phase. This solution pyrolysis method can also be used to prepare aryl diazo esters in high yields. This method is quite useful since the starting keto esters can be readily prepared in large quantities by reaction of the corresponding arylmagnesium bromides with
diethyl oxalate.
20
In a typical procedure,
0.14 g of sodium was dissolved in
10 mL of ethylene glycol by heating to 70°C and
0.0041 mol of tosylhydrazone was added. After heating with vigorous stirring for 5 min at 70–80°C, the mixture was cooled to about 35°C and
15 mL of hexane or ether was added with continued stirring. The organic extract was removed by
pipette and the procedure was repeated a total of 5 times. The combined organic extracts were washed with
30 mL of 5% sodium hydroxide solution, with a saturated sodium chloride solution, and dried over
magnesium sulfate. After filtration, the solvent was removed on a rotary evaporator to leave the diazo compound. Table II gives yields of diazo compounds prepared by this solution pyrolysis method.
TABLE II
FORMATION OF DIAZO COMPOUNDS BY PYROLYSIS OF SODIUM SALTS OF TOSYLHYDRAZONES IN ETHYLENE GLYCOL
|
Tosylhydrazone |
Temperature (°C) |
Product |
Yield (%) |
|
|
70a |
|
90 |
|
80a |
|
77 |
|
70b |
|
86 |
|
70b |
|
88 |
|
70b |
|
76 |
|
70b |
|
94 |
|
a The salt in ethylene glycol was heated at this temperature, cooled, and extracted periodically with hexane.
|
|
c This product was further purified by distillation at less than 0.1 mm. The other products were not distilled.
|
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