JP4434692B2 - Process for producing 5-iodo-2-methylbenzoic acid - Google Patents

Description

  The present invention relates to a highly selective industrial production method of 5-iodo-2-methylbenzoic acid for iodination of 2-methylbenzoic acid. 5-Iodo-2-methylbenzoic acid is a useful compound as a raw material for functional chemicals in addition to pharmaceuticals and agricultural chemicals.

  As a method for synthesizing 5-iodo-2-methylbenzoic acid, a method in which iodine and 2-methylbenzoic acid are reacted in the presence of sodium nitrite and fuming sulfuric acid (see, for example, Non-Patent Document 1), or thallium (III ) A method of reacting potassium iodide with 2-methylbenzoic acid in the presence of trifluoroacetate (see, for example, Non-Patent Document 2) is known. In the method of Non-Patent Document 1, the yield is as low as 18%, and a large amount of a mixture of sodium nitrite and fuming sulfuric acid, which is a strong oxidizing agent, is used as a reaction reagent. Further, in the method of Non-Patent Document 2, since the yield is as low as 33% and a highly toxic thallium salt is used, it is not suitable as an industrial method for producing 5-iodo-2-methylbenzoic acid. is there.

  In addition to the above, the so-called Sandmeyer method (see Non-Patent Document 3, for example) in which aromatic amine is dediazo-iodinated, which is generally known as an iodination technique for aromatic compounds, is once chlorinated or brominated. Halogen exchange method in which iodine exchange reaction is performed later (for example, see Non-Patent Document 4), a method in which iodine monochloride is allowed to act (for example, see Non-Patent Document 5), a method in which iodine and sodium periodate are allowed to act together with an acid catalyst ( For example, application of the nonpatent literature 6 and the patent literature 1 etc. can be considered.

  When synthesizing 5-iodo-2-methylbenzoic acid by the Zandmeier method, it requires a multi-step reaction such as nitration, reduction, diazotization, dediazo-iodination, nitration, diazotization, etc. This process is extremely complicated because of safety issues. In the case of the halogen exchange method, since the reaction requires two steps, the process becomes complicated if a purification step is included. In addition, a large excess of sodium iodide, potassium iodide, or the like is used in the iodine exchange reaction. Since it is difficult to separate and recover the excess, the manufacturing method is expensive.

  The method using iodine monochloride has the feature that the reaction can be carried out in a simple one-step process, but the reaction with an aromatic compound having an electron withdrawing group such as benzoic acid has low reaction activity and high reaction results. Is not obtained. For example, in Non-Patent Document 5, iodination reaction of benzoic acid is performed, but the yield of 3-iodo-benzoic acid as a product is only about 43%, and it is applied to iodination of 2-methylbenzoic acid. Even so, it is difficult to expect a high yield.

  Conventionally, an iodination method using iodine and an oxidizing agent such as iodic acid or periodic acid is known. For example, when a method in which iodine and sodium periodate are allowed to act together with an acid catalyst (see, for example, Non-Patent Document 6), high reaction results have been obtained for aromatic compounds with electron-withdrawing groups. Since a large amount of is used, the load of waste acid treatment after completion of the reaction is large, which is not practical as an industrial production method. Moreover, although it is the same reaction system as a nonpatent literature 6, it is made to react with 2-methylbenzoic acid using the iodine and periodic acid with an acid catalyst as a method of obtaining the monoiodine body of methylbenzoic acid in patent document 1. A method is disclosed. However, according to the examples, the yield is only about 52 to 65%, and the purity of the product is as low as about 95%. Therefore, a further purification step is required to obtain a high-purity product. Is complicated. Although many products are dissolved in the mother liquor after product recovery, it is difficult to separate and recover the catalyst because sulfuric acid, high boilers, and the like coexist. Patent Document 1 discloses a method of recycling a mother liquor into a reaction system. However, according to an example, the product purity is reduced to 90%, which is not an appropriate method. As described above, although the method of Patent Document 1 has an improved aspect, there are still many problems to implement industrially, and the economics of the process remains a question.

In the production of 5-iodo-2-methylbenzoic acid, the isomer 3-iodo-2-methylbenzoic acid is produced as a by-product and it is difficult to separate and purify from 5-iodo-2-methylbenzoic acid. Although there is a problem of impairing purity and isolation yield, none of the above-described prior arts show a method for reducing unnecessary isomers. Examples of the regioselective iodination of aromatic compounds include a method of allowing iodine monochloride to act in the presence of zeolite (for example, see Non-Patent Document 7), a method of oxyiodination in the presence of zeolite (for example, patents). (See Literatures 2 and 3), but none of the reaction selectivity is necessarily satisfactory, and there are a plurality of substituents and 2-methylbenzoic acid having an electron withdrawing group. There are few known examples of reactions for such compounds. As described above, there has been no effective method for producing 5-iodo-2-methylbenzoic acid with high selectivity and high yield based on iodine in the prior art.
Journal of the Indian Chemical Society, 1930, pp 503-504. Journal of the Chemical Society, Perkin Transactions I.D. , 1974, pp2405-2409. Organic Synthesis, Collective Volume. II, 1943, p351 Organic Synthesis, Collective Volume. V, 1973, p478 Russian Journal of Organic Chemistry, 34, 7, 1998, pp 997-999. Bulletin of the Chemical Society of Japan. , Vol. 73, pp 951-956 (2000) Catalysis Letters, 40, 1996, p257 JP 2003-12597 A JP 59-219241 Japanese Translation of National Publication No. 1-502819

  The object of the present invention is to efficiently produce 2-iodo-2-methylbenzoic acid by iodination of the raw material 2-methylbenzoic acid with a simple manufacturing process and high-purity product with high yield. It is to provide an extremely excellent industrial means.

  As a result of intensive studies to solve the above problems, the present inventors have used β-type zeolite, acetic acid, acetic anhydride, iodine, and oxidizing agents such as iodic acid and periodic acid, using 2-methylbenzoic acid as a raw material. The reaction proceeds with high selectivity by carrying out the iodination reaction in the presence of water, and when the reaction is carried out under such iodination conditions, it is possible to combine only the crystallization step of precipitating the product by adding water. The inventors have found that high-purity 5-iodo-2-methylbenzoic acid, which was impossible with conventional methods, can be easily obtained in a high yield, and have completed the present invention.

  According to the method of the present invention, although the raw material is 2-methylbenzoic acid, which is a low activity substrate for electrophilic substitution reactions such as iodination, the reaction proceeds at a high conversion rate, and the object is 5-iodo-2-methylbenzoic acid can be obtained with high selectivity. Furthermore, since the selectivity to the product is high, high-purity 5-iodo-2-methylbenzoic acid can be obtained in a high yield simply by precipitating the product by adding water.

That is, the present invention provides iodine that iodinates 2-methylbenzoic acid under reaction conditions in which β-type zeolite, acetic acid, acetic anhydride, iodine, and at least one of an oxidant composed of iodic acid and periodic acid are present together. The method for producing 5-iodo-2-methylbenzoic acid as shown in (1) to (7), and two methods, which are two steps: a crystallization reaction step and a crystallization step for precipitating the product by adding water, High purity 5-iodo-2-methylbenzoic acid produced by
(1) Iodination reaction in which 2-methylbenzoic acid is iodinated under reaction conditions in which β-type zeolite, acetic acid, acetic anhydride, iodine, and at least one of an oxidizing agent composed of iodic acid and periodic acid are present together A method for producing 5-iodo-2-methylbenzoic acid, characterized in that two steps, a crystallization step of precipitating a product by addition of water and a water addition step, are essential steps.
(2) The method for producing 5-iodo-2-methylbenzoic acid according to (1), wherein 0.1 to 5 parts by weight of water is added to 1 part by weight of the reaction product solution to precipitate the product.
(3) The method for producing 5-iodo-2-methylbenzoic acid according to (1) or (2), wherein a part of the mother liquor after product recovery is recycled to the crystallization step.
(4) The method for producing 5-iodo-2-methylbenzoic acid according to any one of (1) to (3), wherein the β-type zeolite has a Si / Al molar ratio of 20 to 500.
(5) In (4), β-type zeolite has a Si / Al molar ratio of 20 to 500, and a different kind of element from Si, Al, and O deposited in the framework structure exists in or outside the framework. The manufacturing method of 5-iodo- 2-methylbenzoic acid of description.
(6) One or more elements selected from Na, K, Cs, Ca, Mg, Ti, Sn, Fe, Ni, Zn, Pb, and Ag are included in the skeleton structure. The manufacturing method of 5-iodo-2-methylbenzoic acid as described in (5).
(7) The purity of 5-iodo-2-methylbenzoic acid is 99% or more, and the total amount of iodine, iodine compound, inorganic salt, transition metal compound, zeolite, and metal oxide contained as impurities is 500 ppm or less. 5-Iodo-2-methylbenzoic acid produced by the method according to any one of (1) to (6).

  According to the present invention, 5-iodo-2-methylbenzoic acid useful in functional chemical products such as pharmaceuticals can be easily obtained with high purity and high yield. In addition, the production process consisting of reaction, separation and purification is simple in process and has features such as a small purification load, and its significance is very large in industrial implementation.

  In the present invention, 2-methylbenzoic acid used as a reaction raw material is not particularly limited as long as it is industrially available, but in order to increase the purity of the final product, one having a purity of 98% or more is used. It is preferable to do this.

  The iodination reaction is carried out in the presence of β-type zeolite in the presence of iodine and an oxidizing agent such as iodic acid or periodic acid. Although the iodination reaction proceeds even with iodine alone, compounds having an electron withdrawing group such as 2-methylbenzoic acid have low reactivity, so it is necessary to increase the reactivity by coexisting iodic acid or periodic acid. . Iodine, iodic acid, and periodic acid are all solid at room temperature, but they may remain solid when used in the reaction, or they may be dissolved or suspended using an appropriate solvent. .

  The β-type zeolite coexisting during the reaction preferably has a ratio of Si atoms to Al atoms constituting the skeleton of 20 to 500. In addition, elements other than Si, Al, and O that are usually entrusted to the structure of the skeleton, such as elements such as Na, K, Cs, Ca, Mg, Ti, Sn, Fe, Ni, Zn, Pd, and Ag, are naturally or It may be present in the skeleton or outside the skeleton by artificial means such as hydrothermal synthesis or ion exchange / impregnation. Zeolite may be any of crystal powder, compacted and pulverized, extruded, or tableted.

  In the present invention, water is by-produced with the progress of the iodination reaction, but the reaction can be promoted by removing water produced by adding a dehydrating agent, and a high conversion rate can be obtained. As the dehydrating agent, those which act only on water and do not react with other components in the system are preferable. Inorganic compounds such as anhydrous sodium sulfate, anhydrous magnesium sulfate, and calcium chloride, and acetic anhydride, propionic anhydride, pivalic anhydride Examples thereof include acid and carboxylic acid anhydrides such as phthalic anhydride, but it is particularly preferable to use acetic anhydride in view of ease of separation and purification after the reaction.

  In carrying out the present invention, various reaction methods such as a batch method, a semi-batch method, a complete mixed flow method, and a fixed bed flow method can be adopted. The reaction method may be selected according to the production scale of the product. The batch method is appropriate for small-scale production, and the reaction is continuously performed by the complete mixed flow method or fixed bed flow method for mass production. This is a more efficient production method.

  The reaction temperature in the method of the present invention is in the range of 50 to 200 ° C, preferably 70 to 150 ° C. If the temperature is lower than this, the reaction proceeds, but a sufficient reaction rate cannot be obtained. If the temperature is higher than this, side reactions such as the formation of high-boiling substances increase, which is not preferable. The reaction pressure is an absolute pressure in the range of 0.005 to 2 MPa, preferably 0.01 to 1 MPa.

  The melting point of 2-methylbenzoic acid is 105 ° C., and a reaction solvent is not necessarily required when the reaction is performed at a temperature equal to or higher than the melting point, but it is usually preferable to use an organic solvent inert to iodination, Acetic acid, trifluoroacetic acid, dichloromethane, carbon tetrachloride, dichlorobenzene, chlorobenzene and the like are used, and the use of acetic acid is particularly preferable. The amount of the solvent used is preferably 0.5 to 100 parts by weight, more preferably 1 to 50 parts by weight with respect to 1 part by weight of 2-methylbenzoic acid.

  Although there is no restriction | limiting in particular in the usage-amount of iodine, In order to raise the conversion rate of 2-methylbenzoic acid, 0.1-1.5 weight part with respect to 1 weight part of 2-methylbenzoic acid, Preferably it is 0. It is appropriate to use 5 to 1 part by weight. The amount of the oxidizing agent such as iodic acid or periodic acid used is preferably 0.01 to 1 part by weight, more preferably 0.05 to 0.5 part by weight with respect to 1 part by weight of iodine. is there.

  The amount of β-type zeolite used is 0.05 parts by weight or more, preferably 0.1 parts by weight or more with respect to 1 part by weight of 2-methylbenzoic acid as a raw material. When the amount of β-type zeolite used is less than this, sufficient reaction activity cannot be obtained, and 5-iodo-2-methylbenzoic acid cannot be obtained with high selectivity. When the reaction is carried out by suspending the β-type zeolite, the reaction solution after the reaction and the β-type zeolite can be easily separated by a general method such as sedimentation, centrifugation, or filtration. The separated β-type zeolite may be circulated in the reaction system, and at that time, it may be circulated after performing necessary treatments such as removal of adhering organic substances by combustion in air and washing with an appropriate solvent.

  The amount of acetic anhydride used is 0.01 to 2 parts by weight, preferably 0.1 to 1.5 parts by weight, based on 1 part by weight of 2-methylbenzoic acid as a raw material. When the amount of acetic anhydride used is less than this, a sufficient reaction promoting effect cannot be obtained, and the conversion rate of raw materials 2-methylbenzoic acid and iodine cannot be increased. It is not preferable to use more than this because it is uneconomical and the load of separation / recovery in the purification process increases. When iodine, iodic acid, periodic acid, etc. are dissolved or suspended in water and charged into the reactor, in addition to the above amount used, the amount necessary to remove the water used at that time Of acetic anhydride must be added.

In carrying out the method of the present invention, a reaction method such as a batch method, a semi-batch method, a complete mixing flow method, etc. is adopted. Usually, a reaction time in a batch method, a semi-batch method or a complete mixing flow method As the residence time at 1 to 20 hours are employed. In the case of a fixed bed flow system, 0.05 to ¹ h ⁻¹ is usually employed as LHSV (liquid space velocity) of 2-methylbenzoic acid.

  The industrial production process of 5-iodo-2-methylbenzoic acid has two essential steps: an iodination reaction step and a crystallization step for precipitating the product by adding water. After performing the iodination reaction by the above-mentioned method, a high purity product of 5-iodo-2-methylbenzoic acid can be easily isolated by adding water to the product solution to precipitate crystals.

  When 0.1 to 5 parts by weight of water is added to 1 part by weight of the reaction product solution, 90% or more of the generated 5-iodo-2-methylbenzoic acid is precipitated. The precipitated crystals are collected by filtration. When water is added, iodine crystals may precipitate and be mixed with 5-iodo-2-methylbenzoic acid. Sodium sulfite, sodium hydrogen sulfite, sodium thiosulfate, etc. are added to the reaction product solution in advance. Thus, precipitation of iodine can be prevented. The amount of sodium sulfite, sodium hydrogen sulfite, or sodium thiosulfate added is 0.05 parts by weight or less per 1 part by weight of iodine used in the reaction.

  The acetic acid solvent can be easily recovered by distilling the mother liquor after the crystal recovery, and can be reused in the reaction system. Further, 5-iodo-2-methylbenzoic acid dissolved in the mother liquor is concentrated in the bottoms after distillation, and can be recovered by recycling to a crystallization system. Since high boiling substances other than products accumulate in the bottoms, it is necessary to purge some of them without recycling to the crystallization system. In order to increase the recovery of 5-iodo-2-methylbenzoic acid and not impair the product purity, it is appropriate to recycle 50 to 90% of the components in the mother liquor.

  An iodination reaction step in which 2-methylbenzoic acid is iodinated under reaction conditions in which β-type zeolite, acetic acid, acetic anhydride, iodine, and at least one of an oxidizing agent composed of iodic acid and periodic acid are present, and water 5-iodo-2-methylbenzoic acid obtained by a production method having two essential steps of a crystallization step for precipitating a product by addition has a purity of 99% or more and contains iodine, iodine compound and inorganic contained as impurities The total amount of the salt, the transition metal compound, the zeolite, and the metal oxide can be very high purity of 500 ppm or less.

EXAMPLES Hereinafter, although an Example and a comparative example demonstrate this invention further in detail, it is not limited by these examples.
Example 1
A 10 L reaction vessel equipped with a cooling reflux tube was charged with 2678 g of acetic acid, 823 g of acetic anhydride, 700 g of 2-methylbenzoic acid, 502 g of iodine, 299 g of 70% aqueous iodic acid, and 161 g of H-β zeolite, and 4 at a reflux temperature (122 ° C.). Reacted for hours. After completion of the reaction, H-β zeolite was separated by filtration, and 200 g of a 10% aqueous sodium thiosulfate solution and 2500 g of water were added to the filtrate and cooled to 30 ° C. The precipitated crystals were collected by filtration to obtain 1204 g (weight after drying) of the product. As a result of analyzing the recovered crystals and the mother liquor by HPLC (high performance liquid chromatograph), the following reaction results were obtained.
Conversion rate of 2-methylbenzoic acid: 97.0%
5-iodo-2-methylbenzoic acid: yield 94.3%, selectivity 97.2%
3-Iodo-2-methylbenzoic acid: yield 0.7%, selectivity 0.7%
5-Iodo-2-methylbenzoic acid isolated yield: 89.6%
5-iodo-2-methylbenzoic acid purity in the crystal 99.7%
1 g of the crystals obtained above was dissolved in 25 mL of methanol, 25 mL of 4% KI aqueous solution and 5 mL of 17% sulfuric acid were added, and titrated with 0.02 M sodium thiosulfate aqueous solution. As a result, the iodine content was 5 ppm. Further, according to ICP total elemental analysis, Li, Na, K, Mg, Ca, Sr, Ba, Sc, Y, Ti, Zr, V, Nb, Cr, Mo, W, Mn, Fe, Ru, Co, Rh , Ni, Pd, Pt, Cu, Ag, Au, Zn, Cd, Al, In, Si, Sn, Pb, P, Sb, and S are not detected. Met.

Example 2
In the same manner as in Example 1, except for using 3360 g of acetic acid, 322 g of acetic anhydride, 544 g of iodine, and 191 g of periodic acid instead of iodic acid, 1149 g of a reaction product was obtained. As a result of the analysis, the following reaction results were obtained.
Conversion rate of 2-methylbenzoic acid: 93.0%
5-Iodo-2-methylbenzoic acid: Yield 90.0%, selectivity 96.8%
3-Iodo-2-methylbenzoic acid: yield 0.2%, selectivity 0.2%
5-Iodo-2-methylbenzoic acid isolated yield: 85.2%
5-iodo-2-methylbenzoic acid purity in the crystal 99.5%
As a result of analyzing the crystals obtained above, the iodine content was 5 ppm, Li, Na, K, Mg, Ca, Sr, Ba, Sc, Y, Ti, Zr, V, Nb, Cr, Mo, W, Mn Fe, Ru, Co, Rh, Ni, Pd, Pt, Cu, Ag, Au, Zn, Cd, Al, In, Si, Sn, Pb, P, Sb, S are not detected, one genus, and two All the elements of the genus were 1 ppm or less.

Example 3
90% (126 g) of 140 g of the crystals obtained by concentrating and drying the filtrate after recovering the crystals of Example 1 was recycled to the crystallization system. Crystals to be recycled were reacted in the same manner as in Example 1 and dissolved in a solution excluding H-β zeolite, and then 200 g of 10% sodium thiosulfate aqueous solution and 2500 g of water were added and cooled to 30 ° C. The precipitated crystals were collected by filtration to obtain 1228 g of product. The purity of 5-iodo-2-methylbenzoic acid in the crystals was 99.6%. As a result of analyzing the crystal, the iodine content was 5 ppm, Li, Na, K, Mg, Ca, Sr, Ba, Sc, Y, Ti, Zr, V, Nb, Cr, Mo, W, Mn, Fe, Ru, Co, Rh, Ni, Pd, Pt, Cu, Ag, Au, Zn, Cd, Al, In, Si, Sn, Pb, P, Sb, S are not detected. Was 1 ppm or less. Although the crystal of 5-iodo-2-methylbenzoic acid obtained in Example 1 was 1204 g, it was found that the recovery rate could be increased without impairing product purity by recycling the components of the crystallization mother liquor. It was.

Comparative Example 1
Using the same apparatus as in Example 1, 600 g of 2-methylbenzoic acid, 480 g of iodine, 288 g of 50% aqueous periodic acid solution, and 188 g of concentrated sulfuric acid were added to 3680 mL of acetic acid, and reacted at a reflux temperature (120 ° C.) for 7 hours. After cooling to 30 ° C., the precipitated grayish white crystals were collected by filtration to obtain 624 g of a product. As a result of the analysis, the following reaction results were obtained.
2-methylbenzoic acid conversion 94.0%
5-Iodo-2-methylbenzoic acid: Yield 69.0%, selectivity 73.4%
3-Iodo-2-methylbenzoic acid: Yield 20.0%, selectivity 21.3%
5-Iodo-2-methylbenzoic acid isolated yield: 54.0%
5-iodo-2-methylbenzoic acid purity in the crystal 95.0%
Both purity and yield of 5-iodo-2-methylbenzoic acid were low.
As a result of analyzing the crystals obtained above, the iodine content was 620 ppm. Further, according to ICP total elemental analysis, Li, Na, K, Mg, Ca, Sr, Ba, Sc, Y, Ti, Zr, V, Nb, Cr, Mo, W, Mn, Fe, Ru, Co, Rh , Ni, Pd, Pt, Cu, Ag, Au, Zn, Cd, Al, In, Si, Sn, Pb, P, Sb, and S are not detected. Met.

Comparative Example 2
100 g of the 5-iodo-2-methylbenzoic acid purity 95.0% obtained in Comparative Example 1 was dissolved in acetic acid 2000 g at 90 ° C. and cooled to 30 ° C. As a result of collecting 60 g of grayish white crystals precipitated by filtration and analyzing by HPLC, the purity of 5-iodo-2-methylbenzoic acid was 98%. As a result of analyzing the obtained crystals, the iodine content was 545 ppm. Further, according to ICP total elemental analysis, Li, Na, K, Mg, Ca, Sr, Ba, Sc, Y, Ti, Zr, V, Nb, Cr, Mo, W, Mn, Fe, Ru, Co, Rh , Ni, Pd, Pt, Cu, Ag, Au, Zn, Cd, Al, In, Si, Sn, Pb, P, Sb, and S are not detected. Met.

Comparative Example 3
Except not using acetic anhydride, it carried out by the same method as Example 1, and obtained 598g of products. As a result of the analysis, the following reaction results were obtained.
Conversion rate of 2-methylbenzoic acid 65.8%
5-Iodo-2-methylbenzoic acid: yield 60.2%, selectivity 91.5%
3-Iodo-2-methylbenzoic acid: Yield 2.2%, selectivity 3.3%
5-Iodo-2-methylbenzoic acid isolated yield: 45.8%
5-iodo-2-methylbenzoic acid purity in the crystal 95.2%
Both purity and yield of 5-iodo-2-methylbenzoic acid were low.
As a result of analyzing the crystals obtained above, the iodine content was 480 ppm. Further, according to ICP total elemental analysis, Li, Na, K, Mg, Ca, Sr, Ba, Sc, Y, Ti, Zr, V, Nb, Cr, Mo, W, Mn, Fe, Ru, Co, Rh , Ni, Pd, Pt, Cu, Ag, Au, Zn, Cd, Al, In, Si, Sn, Pb, P, Sb, and S are not detected. Met.

Claims (4)

An iodination reaction step in which 2-methylbenzoic acid is iodinated under reaction conditions in which β-type zeolite, acetic acid, acetic anhydride, iodine, and at least one of an oxidizing agent composed of iodic acid and periodic acid are present together; Two crystallization steps of adding 0.1 to 5 parts by weight of water to 1 part by weight of the reaction product solution to precipitate the product are essential steps. A method for producing benzoic acid. The method for producing 5-iodo-2-methylbenzoic acid according to claim 1, further comprising a recycling step of adding crystals obtained by concentrating and drying a part of the mother liquor after product recovery to the reaction product solution. . The method for producing 5-iodo-2-methylbenzoic acid according to claim 1 or 2, wherein the β-type zeolite is a β-type zeolite having a Si / Al molar ratio of 20 to 500. The β-type zeolite is a β-type zeolite in which one or more elements selected from Na, K, Cs, Ca, Mg, Ti, Sn, Fe, Ni, Zn, Pd, and Ag are present in or outside the framework. A process for producing 5-iodo-2-methylbenzoic acid according to claim 3.