Amplification response

For reactions with large thermal effects (even post-processing), scale-up is far more dangerous than small-scale experiments

Enthalpy change: The greater the negative value, the more heat is released, and the more dangerous it is

The amount of materials: when the enthalpy becomes constant, the more the amount of materials, the more the total reaction heat, and the more dangerous the reaction

Environment: If the heat of reaction cannot be quickly absorbed or removed by the environment in which it is located, or the latent heat of reaction is accumulated, the danger is great

For the small test and amplification of the same reaction, because the enthalpy change is a fixed value, to reduce the risk of the amplification reaction with an increase in the amount of materials, only time and environment should be considered, and the reaction time and the reaction environment are actually reacting now.

1.

R&D personnel often have some misunderstandings.

For the violent exothermic amplification reaction, one is to confirm that the added materials have reacted completely, and the unreacted materials in the reaction system must not be allowed to be unreacted; the second is to appropriately control the feeding speed and artificially extend the release time of the reaction heat to make the reaction The heat energy is removed in time and conducted out without accumulating the latent heat of reaction

The accumulation of latent heat of reaction includes two aspects, one is the latent heat of the reaction to be reacted in the reaction liquid that has been mixed together; the other is the heat accumulated in the reaction, where the accumulated heat = the heat produced most-the heat removed

2.

The heat of reaction is generally removed by the refrigerant outside the reactor wall.

Poor heat transfer is the most prominent safety problem in the amplification reaction

In addition to the material of the bottle wall, thickness, stirring speed and method, temperature difference between inside and outside the reactor, and center distance, the factors that determine the heat transfer rate are more importantly the ratio of the heat dissipation area of ​​the reactor to the volume of the reactor (the amount of material).

Reaction latent heat accumulation, filling heat and poor heat transfer are safety issues that must be faced when performing amplification reactions and need to be properly resolved.

In addition to the above-mentioned related problems of reaction latent heat accumulation and heat transfer, the amplification reaction also has problems such as gas release and side reaction formation.

Case 1

The accident reaction formula is as follows:

The reaction has been tested in many batches before, this time it is an amplified reaction
.
73 g of the reaction substrate was dissolved in a mixture of 350 mL of pyridine and 350 L of water, and 120 g of KMnO ₄ was added in portions within half an hour at room temperature according to the feeding speed of the small test
.
After stirring at room temperature for 45 minutes, the reaction began to heat up
.
About two hours later, there was a detonation sound, the balloon above the reaction condenser burst, and the material spewed out.
At this time, the temperature of the oil bath was 60°C, but the reaction liquid boiled strongly by itself
.

Reason analysis: the reaction is severely heat-storing, and the heat conduction is not smooth, which causes the reaction to burst into the material
.
Before the reaction, the reaction mechanism and amplification effect were not carefully considered.
After the reaction was amplified, it was not recognized that the heat of reaction and the amount of gas released would also increase accordingly.
Therefore, it was considered that no accident occurred during the small test, and neither was the amplification effect.
There will be problems
.

Lesson: Before the reaction, you should carefully consider the reaction mechanism and amplification effect, carefully observe the small changes in the reaction temperature of the small test, and anticipate and eliminate possible problems in the reaction as much as possible
.
Do not add balloons for reactions without anhydrous and oxygen-free requirements
.

Case 2

It exploded during the translocation of pyridine nitrogen oxides, and the reaction formula is as follows:

Three batches of small tests were done before the scale-up, 20-120g of solid substrate was fed, and the reflux reaction was performed after the addition of POCl ₃ , and the small test reactions were normal
.
The feed for this amplification reaction is 600g, and 2L POCl ₃ needs to be added
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When zooming in, the operation is the same as that of the small test.
The POCl _{3 is} slowly added to the substrate.
When about 400 mL is added, the reactant is found to boil, and then an explosion occurs.
The explosion will blow up all the items in the fume hood, and the glass of the cabinet door will be shattered
.

Reason analysis: there is a problem with the feeding sequence.
Adding the liquid to the solid is not conducive to stirring and heat dissipation
.
Problems that are not exposed by the small test are likely to be exposed when zooming in
.
The latent heat of reaction accumulates, and the thermal effect accelerates the decomposition and explosion of nitrogen oxides
.

Related link: Safe space in the reactor