Safety countermeasures for reaction heat, latent heat of reaction and threshold temperature (1)

The reaction that emits a lot of heat and has a higher threshold temperature during the reaction is difficult to control

(1) Security countermeasures

(1) For the first type of reaction mentioned above, if there is a violent exotherm regardless of low or high temperature, it is necessary to combine the specific conditions of the reaction and try to slowly feed at a lower temperature, but make sure that every little substrate is added.

Low-temperature feeding, prolonging the feeding time and reaction time are safe operation methods to reduce the risk, and can also reduce the occurrence of side reactions

(2) For the second type, that is, the instantaneous violent exothermic reaction with the characteristic of threshold temperature, after adding a little substrate, it is necessary to make sure that the reaction has started to continue the steady addition of the substrate, and ensure that all the substrates are added.

(3) Appropriate dilution

(4) Changing the reaction mechanism, using suitable catalysts for single-phase catalysis, heterogeneous catalysis or phase transfer catalysis, and biosynthesis (for example, all types of reactions such as enzymatic reactions in the human body are completed gently at 37°C), etc.

(2) Case discussion

1.

The reason why Grignard reactions are dangerous and difficult to control is that they have a very sensitive reaction threshold temperature and a large amount of instantaneous heat of reaction

Safety accidents in Grignard reaction generally occur in the preparation process of Grignard reagents.

Figure 24-7 Security incident image during preparation of Grignard reagent

Whether the initiation process for preparing Grignard reagents is smooth and safe depends on the activity of magnesium, the structure of halogenated hydrocarbons, temperature, concentration, initiator, solvent type and solvent purity (water content), moisture on the inner surface of the instrument and operation, etc.

The safety of the reaction is mainly reflected in the fact that it is necessary to be very sure that the reaction has been initiated before adding a large amount of the halogenated hydrocarbon solution, and to ensure that the added reaction solution can be successfully reacted

Generally speaking, the safety of Grignard reagents in nucleophilic addition reactions is much better

2.

Most substitution reactions are relatively stable.

A researcher took the acetyl chloride method.

Figure 24-8 The scene after the fume hood fire when preparing the hydrochloric acid ethyl acetate solution

The cause of the accident: all the materials were added at low temperature, and because the system temperature was low, the reaction activation energy was not enough, the reaction was not initiated, and a large amount of latent heat of reaction was accumulated.

Similar accidents: The preparation of hydrochloric acid methanol can be done by directly passing dry hydrogen chloride gas in the methanol , or by adding acetyl chloride to the methanol , depending on the convenience of obtaining the material at that time
.
In the latter method, acetyl chloride should be added dropwise at 0-5°C (in fact, 0°C can be regarded as the critical reaction temperature of the reaction), so that the generated oxygen chloride is dissolved in methanol to become the required alcohol solution in hydrochloric acid
.
A researcher took the method of dripping acetyl chloride.
He added 500 mL of acetyl chloride to 500 mL of methanol at -20～-25℃.
When the temperature was about halfway, he observed that the temperature did not rise, so he finished the addition of acetyl chloride in one go.
Acid chloride
.
About half an hour later, the reaction broke out suddenly, the material was flushed instantly, and sparks were generated when encountering electrical appliances, which caused a fire in the air hood (Figure 24-9)
.

Figure 24-9 The scene after a fume hood fire in the preparation of hydrochloric acid methanol

3.
Nitration reaction

The nitrification reaction is mostly a strong exothermic reaction.
The larger the scale, the more difficult it is to control.
Explosion accidents of nitrification reactions in factory workshops often occur and reported.
Even small-scale nitrification reactions in the laboratory, accidents also occur from time to time
.

According to the literature, fuming nitric acid (300 mL) was added to the reaction flask and cooled to -20°C with a dry ice-acetone bath
.
Compound A (100 g, 0.
52 mmol) was added in batches, and the reaction temperature was controlled to be -18°C to -20°C
.
After the addition was completed, the reaction mixture was stirred at -20°C for 3 hours
.
Then, remove the cold bath and let it heat up naturally
.
In the process of heating up, the reaction suddenly exothermed violently, producing a lot of smoke, and then it caught fire and burned
.
As shown in Figure 24-10 (screenshot of accident video) and Figure 24-11
.

Reason analysis: The initial temperature of the reaction is set too low, which leads to a large reserve of reaction latent heat
.
When the temperature rises slowly, the reaction threshold temperature is reached and the reaction suddenly erupts, leading to material flushing
.
At the same time, nitric acid enters the acetone and exotherms violently
.
Eventually it caused a fire
.

Lesson: The reaction temperature during feeding should be appropriately increased so that every time a little bit of substrate is added, it will react without accumulating latent heat of reaction
.
If you need to optimize the nitrification selection and location and you must use low temperature and slow reaction, you must also use chromatographic methods such as dot plate and refer to the ratio of the added amount of the material to the product to judge the progress of the reaction, and ensure that the small amount of material added is basically reacted before it can continue to be continued.
​​​​​​​​ ​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​& Plus, you can't blindly mix all the materials together and raise the temperature step by step
.