Novel solid-state representation of at least one phenol derivative and method for obtaining same

Abstract

The present invention relates to novel solid display forms of phenol derivatives characterized by rounded and flattened portions. The resulting compositions have advantageous properties for storage, handling, and compound flow. The present invention also relates to methods for preparing these solids and their use, particularly in the polymer and agri-food industries. [Selection diagram] Figure 5

Description

[Technical Field]

[0001] The present invention relates to novel solid forms of at least one phenol derivative having at least one rounded portion and one flat portion. The present invention also describes a method for preparing these solid forms having at least one rounded portion and one flat portion. The present invention also relates to these solid forms obtained by this method. [Background technology]

[0002] Phenol derivatives, such as vanillin, ethyl vanillin, hydroquinone, catechol, para-methoxyphenol, etc., are present in many industrial sectors: they are used, for example, by the agri-food industry as flavorings or in the polymer industry as polymerization inhibitors.

[0003] Currently, these compounds are mainly sold in powder form. International Publication No. 2016 / 033157 describes a method for shaping hydroquinone into crystalline powder form. This powder consists of small, brittle needle-like crystals, resulting in a significant amount of fines, which causes problems in storage, handling, and transportation. Although the caking resistance of this product is indeed slightly improved, handling this compound poses a risk of irritation, especially to the eyes, respiratory system, or skin.

[0004] Alternative forms have been proposed. JP 2000 / 302716 describes a granulation technique that consists in passing the powder between two rollers, which makes it possible to obtain platelets, and then crushing these platelets to obtain granules. The disadvantage of this method is that dust can remain, either due to the passage through the rollers of the compactor or due to the grinding of the platelets in the crusher. In addition, the granules are compressed and their dissolution rate is very low compared to the original powder.

[0005] Documents EP 0689772 and WO 2004 / 039758 describe the shaping of phenolic compounds, particularly hydroquinone and vanillin, into beads by a prilling process. These beads are highly spherical. This particular shape confers the beads with the advantageous property of resistance to abrasion, thus avoiding the formation of large amounts of dust. The prilling process for preparing these compounds consists in cooling droplets of the phenolic compound in a gas stream to solidify them. The dissolution rate of these beads could be improved for some specific applications.

[0006] Moreover, despite the perceived advantages of these alternative methods, they are costly. It is therefore desirable to propose other alternatives that have a lower economic impact while maintaining good storage, handling, transport, resistance to grinding and resistance to caking properties, reducing health and environmental risks by minimizing the presence of dust and fines, and improving the dissolution properties of these formulations. Summary of the Invention

[0007] It is to the credit of the Applicant Company that they have identified a novel solid display form which exhibits good dissolution characteristics while maintaining all of the above desired properties, particularly good resistance to grinding characteristics.

[0008] The first aspect of the present invention is a compound of formula (I) TIFF0007813578000001.tif55170 (in the formula: n is between 0 and 5, preferably between 0 and 4, and preferentially n is equal to 0, 1 or 2, R1 is selected from the group consisting of hydrogen, alkyl and alkenyl, preferably R1 is selected from hydrogen, methyl and ethyl; - R2 is selected from the group consisting of hydroxyl, alkyl, alkenyl, alkynyl, alkoxy, formyl and acyl, preferably R2 is selected from hydroxyl, methyl, ethyl, propyl, methoxy, ethoxy and formyl. and and a novel solid display shape comprising at least one rounded portion and one flat portion.

[0009] According to another aspect, the present invention provides a process for the preparation of novel solid state display forms comprising at least one compound of formula (I), comprising at least the following successive steps: (a) disposing a liquid droplet comprising at least one compound of formula (I) on a flat surface; (b) solidifying the droplets on the surface. The present invention relates to a method comprising:

[0010] Finally, the present invention relates to the novel solids obtainable by the process of the present invention.Finally, the present invention relates to the use of these novel solids in industry. [Brief explanation of the drawings]

[0011] [Figure 1-2] 1 shows two cross-sectional views of an embodiment of a solid state compound according to the present invention. [Figure 3] 1 shows a top or bottom view of a solid compound according to the present invention. [Figure 4] 1 is a photograph (optical microscope, 6.3x magnification) of pellets of para-methoxyphenol according to the invention obtained on a stainless steel surface. [Figure 5] 1 is a photograph (optical microscope, 6.3x magnification) of pellets of para-methoxyphenol according to the invention obtained on a PTFE coated surface. DETAILED DESCRIPTION OF THE INVENTION

[0012] In the context of the present invention, and unless expressly stated otherwise, the expression "between" includes the boundary.

[0013] In the context of the present invention, and unless otherwise stated, the expression "alkyl" denotes a linear or branched saturated hydrocarbon chain containing 1 to 6 carbon atoms.

[0014] In the context of the present invention, and unless otherwise stated, the expression "alkoxy" denotes OR, wherein R is an alkyl group as defined above.

[0015] In the context of the present invention, and unless otherwise stated, the expression "alkenyl" denotes a linear or branched unsaturated hydrocarbon chain containing 1 to 6 carbon atoms and having at least one double bond between two carbon atoms.

[0016] In the context of the present invention, and unless otherwise stated, the expression "alkynyl" denotes a linear or branched unsaturated hydrocarbon chain containing 1 to 6 carbon atoms and having at least one triple bond between two carbon atoms.

[0017] In the context of the present invention, the term "comprising" may have the meaning "consisting of".

[0018] In the context of the present invention, the term "ambient temperature" means a temperature between 19°C and 24°C, preferably ambient temperature is equal to 20°C.

[0019] According to a first aspect, the present invention provides a compound of formula (I) TIFF0007813578000002.tif56170(in the formula: n is between 0 and 5, preferably between 0 and 4, and preferentially n is equal to 0, 1 or 2, R1 is selected from the group consisting of hydrogen, alkyl and alkenyl; R2 is selected from the group consisting of hydroxyl, alkyl, alkenyl, alkynyl, alkoxy, formyl and acyl. and and a novel solid display shape comprising at least one rounded portion and one flat portion.

[0020] According to a preferred embodiment, R1 is selected from hydrogen, methyl and ethyl. According to another preferred embodiment, R2 is selected from hydroxyl, methyl, ethyl, propyl, methoxy, ethoxy and formyl.

[0021] According to a preferred embodiment of the invention where n=2, the R2 groups, which may be identical or different, are placed one in the ortho position and the other in the para position relative to the OR1 group.

[0022] According to another embodiment of the invention, where n=1, the R2 group is placed in the ortho or para position relative to the OR1 group.

[0023] According to a preferred embodiment, the compound of formula (I) is selected from the group consisting of hydroquinone, catechol, resorcinol, pyrogallol, 4-tert-butylcatechol, tert-butylhydroquinone, para-methoxyphenol, butylhydroxyanisole, vanillin, ethyl vanillin, and a compound of vanillin and ethyl vanillin in a molar ratio of 2. Preferably, the compound of formula (I) is selected from the group consisting of hydroquinone, catechol, resorcinol, pyrogallol, 4-tert-butylcatechol, tert-butylhydroquinone, para-methoxyphenol, and butylhydroxyanisole. Alternatively, the compound of formula (I) is selected from the group consisting of vanillin, ethyl vanillin, and a compound of vanillin and ethyl vanillin in a molar ratio of 2.

[0024] According to a preferred embodiment, the compound of formula (I) is a polymerization inhibitor.

[0025] According to another preferred embodiment, the compound of formula (I) is a flavoring agent.

[0026] According to one aspect of the present invention, the novel solid state represented form may comprise one, two or three compounds of formula (I) as defined above, preferably the novel solid state represented form according to the present invention comprises a compound of formula (I) or a mixture of two compounds of formula (I).

[0027] When the novel solid state display form according to the present invention comprises two compounds of formula (I), the molar ratio between the two compounds is 1:99 to 99:1. According to one particular embodiment, the molar ratio between the two compounds is 1:1 or 2:1.

[0028] When the novel solid display form according to the invention comprises two compounds of formula (I), the mass ratio is strictly greater than 0% by weight, preferably greater than or equal to 0.1% by weight, more preferentially greater than or equal to 5% by weight and strictly less than 100% by weight.

[0029] According to a particular embodiment, the novel solid display form according to the present invention may comprise at least one additive selected from the group consisting of antioxidants, antifoaming agents, corrosion inhibitors, rust inhibitors, surfactants, detergents, dispersants, antifouling agents, diluents, thickeners, or pH adjusters.

[0030] According to a particular embodiment, the novel solid display form according to the present invention may comprise at least one compound selected from the group consisting of a tocopherol derivative, preferably α-tocopherol, β-tocopherol, γ-tocopherol, δ-tocopherol, a copper complex having an oxidation state of 2, preferably copper acetate (Cu(OAc)2) or copper dibutyldithiocarbamate (CB), 2-sec-butyl-4,6-dinitrophenol, phenylenediamine, TEMPO, TEMPO-OH, 2,4-dimethyl-6-tert-butylphenol (Topanol A), phenothiazine, butylhydroxyanisole (BHA), and 2,6-di-tert-butyl-4-methoxyphenol (DTBHA).

[0031] Advantageously, the novel solid display form according to the invention comprises: - 50 to 100% by weight of at least one compound of formula (I) as defined above, - 0 to 50% by weight of at least one compound selected from the group consisting of tocopherol derivatives, preferably α-tocopherol, β-tocopherol, γ-tocopherol, δ-tocopherol, copper complexes having an oxidation state of 2, preferably copper acetate (Cu(OAc)2) or copper dibutyldithiocarbamate (CB), 2-sec-butyl-4,6-dinitrophenol, phenylenediamine, TEMPO, TEMPO-OH, 2,4-dimethyl-6-tert-butylphenol (Topanol A), phenothiazine, butylhydroxyanisole (BHA) and 2,6-di-tertbutyl-4-methoxyphenol (DTBHA), Includes.

[0032] According to another particular embodiment, the novel solid display form according to the invention may comprise at least one additive selected from the group consisting of fatty substances, waxes, sugars, starches, polysaccharides such as maltodextrins and antioxidants.

[0033] The novel solid representation form of the present invention can be represented diagrammatically as shown in Figures 1 and 2. Distance d1 represents the maximum distance between two points A and B on the flat portion of the novel solid representation form. Distance d2 represents the maximum distance between the flat portion and the rounded portion. The novel solid representation form of the present invention can be likened to a spherical cap.

[0034] The rounded portion of these novel solid displayed forms is preferably spherical, although it may have imperfections. The novel solid displayed forms according to the present invention may be described as pellets.

[0035] According to the present invention, the novel solid shape has at least one rounded portion and one flat portion, and therefore according to the present invention, the novel solid shape has edges.

[0036] According to a particular embodiment of the present invention, the flat portion, top view or bottom view, of the novel solid display form as shown diagrammatically in FIG. 3 may have a shape resembling a disk or an oval.

[0037] The volume of the spherical cap is given by: TIFF0007813578000003.tif19170 (where d1 is the diameter of the spherical cap (see Figure 3) and d2 is the thickness of the spherical cap) It can be calculated according to:

[0038] The novel solid form according to the present invention is therefore a sphere of radius r (V=4πr 3 / 3) or to a portion of an ellipsoid (V=4πabc / 3, where a, b, and c are the lengths of the semi-axes of the ellipsoid). The volume of this portion is therefore The following formula: TIFF0007813578000004.tif16170 (wherein x is strictly greater than 0, preferably greater than or equal to 0.01, more preferentially greater than or equal to 0.02, and x is strictly less than 1, preferably less than or equal to 0.9, more preferentially less than or equal to 0.8) According to one particular embodiment, x may be between 0.01 and 0.1.

[0039] According to a particular embodiment of the invention, d1 and d1', identical or different, are between 300 μm and 10,000 μm, preferably between 500 μm and 5000 μm, more preferentially between 500 and 2000 μm; d2 is between 50 μm and 10,000 μm, preferably between 75 μm and 5000 μm, more preferentially between 75 μm and 2000 μm.

[0040] According to the present invention, the flat portions of the novel solid forms are continuous planes. Preferably, the planes represent at least 5%, preferably at least 10%, 15%, 20%, 25%, 30%, 40%, 50% of the total surface of the novel solid forms according to the present invention. Preferably, the planes represent at most 95%, preferably at most 90%, 85%, 80%, 75%, 70%, 60%, 55% of the total surface of the novel solid forms according to the present invention.

[0041] The present invention also relates to a method for preparing the novel solid display form as defined above by a pelletization process. Documents US 2017 / 0326760 and EP 1042056 present two devices suitable for preparing pellets according to the invention.

[0042] According to one particular embodiment, the method comprises at least the following steps: (a) disposing a liquid droplet comprising at least one compound of formula (I) on a flat surface; (b) solidifying the droplets on the surface. Includes.

[0043] Step (a) is a step of placing the droplets on a flat surface. In the context of the present invention, the flat surface can be a belt, a plate or a disk. Preferably, the belt or disk is moving.

[0044] The belt may be a conveyor belt that rotates around two rolls, the belt undergoing translational motion, and the droplets being deposited on an upper portion of the conveyor belt.

[0045] Alternatively, the disc may rotate about an axis, preferably the axis of rotation is perpendicular to the ground. The droplets are deposited on a surface of the disc, preferably the upper surface.

[0046] Advantageously, the method of the present invention further comprises, before step (a), a step (a1) in which at least one compound of formula (I) is melted. During step (a1), at least one compound of formula (I) is heated to a temperature 1°C to 50°C above its melting point or, in the case of a mixture, the melting point of the compound with the highest melting point, preferably 1°C to 20°C above its melting point or the melting point of the compound with the highest melting point, and more preferentially 1°C to 10°C above its melting point or the melting point of the compound with the highest melting point. Generally, the heating temperature can be 50°C to 300°C, preferably 50°C to 260°C.

[0047] One additive or several additives as defined above may be added to the preparation of the compound in molten form.

[0048] The method of the present invention may also include step (a2) of forming droplets. The droplet forming device may be a perforated cylinder or a perforated plate. The droplet forming device is preferably maintained at a temperature equal to or higher than the temperature of step (a1). Preferably, the droplet forming device is placed above a plane so that the droplets can fall onto the plane.

[0049] According to one particular embodiment, step (a1) is carried out before step (a2). According to another embodiment, the droplet formation step (a2) is carried out immediately after the preparation or purification process of the compound of formula (I). In this embodiment, the compound of formula (I) is in liquid form without the need for a step in which the compound of formula (I) is melted.

[0050] Step (b) is a step of solidifying the droplets on the flat surface. Advantageously, the flat surface is cooled to a temperature strictly below the melting point of the compound of formula (I) or, in the case of a mixture, strictly below the melting point of the compound of formula (I) with the lowest melting point. Advantageously, the flat surface is cooled to a temperature between -50°C and a temperature strictly below the melting point of the compound of formula (I) or, in the case of a mixture, strictly below the melting point of the compound of formula (I) with the lowest melting point, preferably between 0°C and a temperature strictly below the melting point of the compound of formula (I) or, in the case of a mixture, strictly below the melting point of the compound of formula (I) with the lowest melting point, more preferentially between 10°C and a temperature strictly below the melting point of the compound of formula (I) or, in the case of a mixture, strictly below the melting point of the compound of formula (I) with the lowest melting point. Preferably, the flat surface is cooled to a cooling temperature between 10°C and ambient temperature.

[0051] According to a particular aspect of the invention, the cooling temperature of the plane is uniform across the entire plane. According to another particular aspect, the cooling temperature is not uniform across the entire plane, but the temperature may have a cooling gradient or cooling zones where the plane is cooled to different cooling temperatures.

[0052] According to one particular embodiment, the flat surface may be subjected to a surface treatment before the process according to the invention. The flat surface may also be coated with a particularly non-stick or hydrophobic coating, such as PTFE (polytetrafluoroethylene). The flat surface may also have a roughness. These treatments or roughnesses make it possible in particular to improve the detachment of the novel solid forms according to the invention at the end of the process. These treatments or roughnesses also make it possible to improve the mechanical properties of the novel solid forms according to the invention, in particular to better resist friability during handling operations. The shape of the solids according to the invention also makes it possible to reduce the caking phenomenon.

[0053] At the end of solidification step (b), the novel solid representative form according to the present invention may be fixed to the surface. The method according to the present invention may include a step in which the novel solid representative form is removed from the surface. The device for forming the novel solid representative form according to the present invention may include a knife or scraper.

[0054] According to a particular aspect of the invention, the process can be carried out in air, under oxygen or under a controlled atmosphere, in particular where the humidity can be controlled. The process according to the invention can be carried out under dry air or under an inert atmosphere, in particular under nitrogen.

[0055] At the end of the process according to the invention, the content of fine particles having a size of less than 355 μm is less than 30% by weight, preferably less than 20% by weight, more preferentially less than 10% by weight, and even more preferentially less than 0.1% by weight, relative to the weight of the novel solid display form of formula (I).

[0056] The method according to the invention may also comprise a step in which fine particles, having a size of 355 μm or less, are separated by sieving or by cyclonic separation. The fine particles may be recycled.

[0057] The novel solid compounds according to the invention have a hardness of at least 1 N. The hardness can be measured with a penetrometer.

[0058] Advantageously, the novel solid compounds according to the invention have a friability of 15% or less. This parameter allows easier handling of these novel solid compounds compared to powders, since mist formation is avoided or at least reduced. Friability can be measured by mixing the novel solid manifestations according to the invention in a triple-shaft mixer for 10 minutes, then measuring the content of particles smaller than 100 μm produced. Friability represents the ratio of the mass of particles smaller than 100 μm produced to the total mass of the novel solid manifestations introduced into the triple-shaft mixer.

[0059] The novel solid state displayed forms according to the present invention have good dissolution properties: the dissolution rates of these solids are at least equal to, and preferably better than, the dissolution rates of other existing forms of the compound of formula (I).

[0060] The chemical composition of the novel solid display forms according to the present invention depends on the liquid composition as defined above.

[0061] The addition of additives as defined above in the novel solid display forms according to the invention can be carried out during the preparation of the composition comprising at least one compound of formula (I) in liquid form (step (a1)) or in an additional step at the end of the process.

[0062] The novel solid state display forms comprising at least one compound of formula (I) as defined above, obtainable according to the process of the invention, are also one subject of the present invention.

[0063] Finally, the present invention relates to the use of these novel solid display forms comprising at least one compound of formula (I) in industry, in particular in the polymer, agri-food, perfume or pharmaceutical industries. [Example]

[0064] Pellets of para-methoxyphenol (PMP) are prepared. The PMP is first melted at 80°C. Small droplets are then formed and deposited on a belt cooled to 18°C.

[0065] 4 and 5 show pellets according to the invention.

[0066] Example 1: The pellets of Figure 4 were obtained on a stainless steel belt.

[0067] Example 2: The pellets of Figure 5 were obtained on a PTFE coated belt.

[0068] TIFF0007813578000005.tif78170

[0069] Resistance to caking is obtained visually after storage of the samples at 35° C. for 7 days.

[0070] The dissolution rate corresponds to the time required to dissolve 90% of 2 g of pellets / powder / flakes in 100 g of water / acrylic acid at 20° C. stirred at 300 rpm.

Claims

1. Formula (I) (In the formula: n is 0 to 5, -R １ is selected from the group consisting of hydrogen, alkyl and alkenyl; -R ２ is selected from the group consisting of hydroxyl, alkyl, alkenyl, alkynyl, alkoxy, formyl, and acetyl. and A solid having a shape comprising at least one rounded portion and one flat portion, said solid being processed by at least the following successive steps: (a) disposing a liquid droplet comprising at least one compound of formula (I) on a flat surface; (b) solidifying the droplets on the flat surface. A solid obtained by a preparation method comprising:

2. 2. A solid according to claim 1, characterized in that the compound of formula (I) is selected from the group consisting of hydroquinone, catechol, resorcinol, pyrogallol, 4-tert-butylcatechol, tert-butylhydroquinone, para-methoxyphenol, butylhydroxyanisole, vanillin, ethyl vanillin and a compound of vanillin and ethyl vanillin in a molar ratio of 2.

3. 3. A method for preparing the solid of claim 1 or 2, comprising at least the following successive steps: (a) disposing a liquid droplet comprising at least one compound of formula (I) on a flat surface; (b) solidifying the droplets on the flat surface. A preparation method comprising:

4. The method of claim 3 , wherein the flat surface is a band, a plate, or a disk.

5. 5. The method of claim 3 or 4, further comprising a step (a1) prior to step (a), wherein said at least one compound of formula (I) is heated to a temperature of 1° C. to 50° C. above its melting point.

6. The method of any one of claims 3 to 5, comprising, before step (a), a step (a2) of forming droplets.

7. 7. A method according to any one of claims 3 to 6, wherein the flat surface is cooled to a temperature strictly below the melting point of the compound of formula (I) to allow solidification of the droplets.

8. The method of any one of claims 3 to 7, carried out in air, oxygen, oxygen-depleted air, a controlled atmosphere, or an inert atmosphere.

9. 3. Use of a solid according to claim 1 or 2 in the polymer, agri-food, perfume or pharmaceutical industry.

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