文献报告秦亚楠

20121125

Influence of Ultrasound on the Nucleation of Polymorphs of

p-Aminobenzoic Acid

Sandra Gracin, Marketta Uusi-Penttila, and Åke C. Rasmuson*

Department of Chemical Engineering and Technology,

Royal Institute of Technology, S-10044 Stockholm, Sweden

Received February 12, 2005; Revised Manuscript Received May 24, 2005

参考文献

背景及主要研究内容

针状 棱柱状

易于成核

二聚体

低 S ，水，乙酸

乙酯

四元环 α-form α-form β-form β-form

<25⁰C

>25⁰C

研究不同超声方案对其成核的影响

背景及主要研究内容

the duration of each pulse,

Δtson

the pulse repetition period,

PRP

the percentage ofMaximum intensity （ % MI ）

超声

P = ({dT}/{dt})mcp

I = P/A

overall sonication exposure (OSE),

实验部分

实验部分

Teq= 40, 38, 36,32, 30, and 20 °C constant cooling rate of 1 °C/min, one without sonication and the other applying sonication sonication scheme (1/9-80)started as the cooling began and wasstopped after nucleation had occurred

MSZW

Eight series of induction time experiments were performedto examine how the intensity of sonication, the temperature, and the supersaturation level influence induction time and the polymorphic form that crystallizes

inductiontime

实验部分

PRP%MI

the temperature Tson , chosen with respect to the desired supersaturation

and always at least a few degrees above the expected metastable zone limit

实验部分

ResultsNucleation Temperature

α + β

（ 1 ）超声存在，出晶温度 增大，即介稳区变窄（ 2 ）超声存在，结果更具 重复性（ 3 ）超声存在，平衡温度 20⁰C ， α + β ；其余 均是 α

Results

Induction Time only the β –form appears The shortest induction time was

6 minutes ， corresponding to the highest average ultrasound Intensity

the induction time without ultrasound is 25-360 min for the α -form and 240-1140 min for the β -form at the same temperature

and supersaturation the induction time quite clearly

decreases with increasing average sonication intensity

Results

the supersaturation is higher

than in series 1-3, and the

measured induction times were

much shorter crystallized form is always α. the β-form is obtained at lower

supersaturation and the α-form

is obtained at higher

supersaturation the induction time decreases as

the average intensity increases

Results

• In series 5, the induction time

decreases quite strongly with

increasing average sonication

intensity from 25 to 2.5 min.

• the polymorphic form that

crystallizes shifts from the β-form

at lower intensity to the α-form at

higher intensity

• in series 6 the induction time is

longer and less dependent on the

sonication intensity

• In series 6 the crystallized form is

always β

Results

• In series 7, the induction times are fairly long but clearly decrease with increasing average sonication intensity.

• in series 7, β-form is obtained.• at moderate supersaturation, the

sonication leads to that the β-form can be produced even above the transition temperature

• in series 8, at low intensity, the β-form is obtained, and at high intensity, the α-form is produced

• The threshold supersaturation for production of the β-form, tends to decrease with increasing temperature.

Discussion

Ultrasonic treatment at all levels of intensity of the present work significantly

shortens the induction time for nucleation of both polymorphic forms

the induction time in general decreases with increasing ultrasound intensity,

that the influence of ultrasound is more pronounced at low supersaturation,

and that the detailed format of the supply of the ultrasonic energy is less

important

sonication clearly favors the formation of the β-form

When the supersaturation is close to the threshold, the intensity of the applied

ultrasound may influence the polymorphic form that crystallizes, and in these

cases a lower intensity promotes the appearance of the β-form

Discussion

Depending on the solvent, it is well-known that carboxylic acids tend to form centrosymmetric dimers in solution

We believe that the kinetic preference for formation of the α-polymorph even below the transition temperature is due to the presence in the solution of such centrosymmetric dimer precursors

In dilute benzoic acid solutions, higher pressures and higher temperatures weaken the hydrogen bonds of the dimers and hence favor the dissociation of the hydrogen-bonded carboxylic acid dimers

In addition, there are several studies on the influence of ultrasound on acetic acid dimerization, where it has been found that the absorbed ultrasonic energy generates a shift in the dimer-monomer distribution in favor of the chain complex dimers and free monomers according to the scheme presented in Figure 8

Discussion

Discussion

We assume that the same may apply to PABA. Hence, an interesting possible explanation to that fact that sonication preferentially promotes the crystallization of the β-form is that sonication reduces the centrosymmetric carboxylic acid dimerization in solution, possibly as a result of the high pressure and temperatures at the collapse of the cavities in accordance with the hot spot theory.

Another interesting aspect is the report that polarized laser light promotes the crystallization of the thermodynamically more stable but kinetically less favorable γ-polymorph of glycine.

The γ -polymorph structure consists of helical chains of roughly parallel head-to-tail glycine molecules. Without polarized laser light the γ -polymorph of glycine whose structure consists of hydrogen-bonded double layers, whose basic unit is a hydrogen-bonded dimer (two antiparallel glycine molecules) will nucleate

Discussion

It is suggested that the influence of the polarized laser light is due to partial alignment of solute molecules because of an interaction between the solute molecules and the laser-induced electric field.

In addition, it has been found that gas-phase samples of PABA that are subjected to laser radiation show the disruption of centrosymmetric hydrogen-bonded Dimers

On the other hand, there are significant electrical field gradients during the collapse of a bubble, and these are strong enough to cause bond breakage and chemical activity.

Hence, the preferential crystallization of the β-polymorph of PABA can perhaps also be explained as being the result of the disruption of PABA dimers by the ultrasound-induced electric field.

Conclusions

In the present study, it is shown that sonication significantly reduces the induction time for nucleation of PABA crystallized in aqueous solutions.

In addition, it is shown that sonication changes the relationship between the nucleation kinetics of the α-form and the β-form in favor of the latter.

Below the transition temperature at 25 °C, the crystallization of the β -polymorph becomes faster and more reproducible when ultrasound is applied.

The induction time decreases with increasing sonication intensity By application of ultrasound, the β –polymorph can also be crystallized

above the transition temperature, as long as the supersaturation is not too high.

Close to the critical supersaturation threshold, there is a threshold in sonication intensity, above which pure β -form is not obtained.

Overall there is an influence of the sonication average intensity, but there is no evidence that the more detailed format by which the ultrasound energy is supplied has an influence.

Conclusions

There are several reports in the literature showing that sonication may reduce the induction time for nucleation. However, to our knowledge this is the first time in solution crystallization that it has been shown that ultrasound may have an influence such that one polymorph in particular is promoted.

Our hypothesis is that this effect is due to an influence on the solute structuring in the solutions the clustering that precedes the nucleation of the two polymorphs. The α-form structure is based on centrosymmetric carboxylic acid dimers. It is believed that the tendency to form dimers in the solution explains why there is a strong preference for the formation of the α-polymorph in an ordinary crystallization.

When ultrasound is applied, it is known from the literature that this dimerization tends to decrease, and it is our hypothesis that this is the explanation for the increased opportunity for the β-form to appear when the crystallizing solution is exposed to ultrasound.

Thank You!