CN117865787A

CN117865787A - Crystal form I of menatetrenone and preparation method thereof

Info

Publication number: CN117865787A
Application number: CN202311813636.3A
Authority: CN
Inventors: 沙薇; 张豪龙; 王永兴; 刘洋; 吕中超
Original assignee: Zhengzhou Taifeng Pharmaceutical Co ltd
Current assignee: Zhengzhou Taifeng Pharmaceutical Co ltd
Priority date: 2023-07-14
Filing date: 2023-12-27
Publication date: 2024-04-12

Abstract

The invention relates to a tetraenemenadione crystal form I and a preparation method thereof, wherein the X-ray powder diffraction diagram of the crystal form I is 6.29+/-0.2 degrees in 2 theta value; 11.63 soil 0.2 °;12.49±0.2°;13.94±0.2°;14.46 soil 0.2 °;14.78 soil 0.2 °;15.63±0.2°;17.05±0.2°;18.47±0.2°;18.81±0.2°; 19.12.+ -. 0.2 ^° The method comprises the steps of carrying out a first treatment on the surface of the 19.50 + -0.2 °;20.08±0.2°;20.82±0.2°; 22.11+ -0.2 °;22.43±0.2°;23.21±0.2°;23.43±0.2°; 24.37+ -0.2 °;25.43 soil 0.2 °;26.34 earth 0.2 °;27.74 earth 0.2 °;28.07 soil 0.2 °;28.86 earth 0.2 °;30.09 soil 0.2 °;31.43±0.2°;32.03 + -0.2 °;32.75±0.2°;34.07 + -0.2 °;34.78±0.2°;36.86±0.2°;37.88 the earth has a diffraction peak at 0.2 °. The invention has the advantages that the crystallization condition of the invention has the advantages of simultaneously obtaining high yield and high purity, and the stability is far higher than that of an amorphous state, thereby being suitable for long-term storage or preparation production.

Description

Crystal form I of menatetrenone and preparation method thereof

Technical Field

The invention relates to the technical field of vitamin K2 preparation for treating osteoporosis and preventing arterial calcification, in particular to a tetraene menadione crystal form I and a preparation method thereof.

Background

Tetramenatetrenone is also called vitamin K ₂ Is a naturally occurring vitamin containing menaquinone basic structure and having anti-hemorrhagic effect, and vitamin K in nature is found in Dai M of 1929 ₁ And K ₂ Both are naphthoquinone compounds. Vitamin K2 is a fat-soluble vitamin, and a derivative of naphthoquinone group with phylloquinone bioactivity is one of important vitamins indispensable in human body. The product is yellow crystal or oily liquid, is insoluble in water, is easily dissolved in organic solvent and vegetable oil, and is heat-resistant but easily damaged by light. Vitamin K ₂ The structure of (2) is as follows:

through research, vitamin K ₂ Has the effects of promoting calcium absorption, inhibiting bone absorption caused by osteoclast, increasing bone density, and preventing and treating osteoporosis. Vitamin K deficiency can cause bleeding and prolonged use of broad-spectrum antibiotics can lead to vitamin K deficiency in vivo. Is liable to cause osteoporosis and arterial calcification. Vitamin K deficiency can cause bleeding and prolonged use of broad-spectrum antibiotics can lead to vitamin K deficiency in vivo. Is liable to cause osteoporosis and arterial calcification.

The original manufacturer, japan Kagaku, discloses a prescription process and application of the menatetrenone. The synthesis and purification methods of menatetrenone are reported in CN 104513149a and patent WO2007032378A1, but specific crystal forms and detailed preparation methods are not reported. Journal, patent and technical documents related to the compound are not reported on the crystal forms and the obtaining methods.

Disclosure of Invention

The crystallization condition of the invention has the advantages of simultaneously obtaining high yield and high purity, the solid product obtained by crystallization has a crystal form which is not reported, and meanwhile, the stability is far higher than that in an amorphous state through stability investigation, so that the crystallization condition is suitable for long-term storage or preparation production.

The invention is realized by the following technical scheme: providing a crystalline form I of menatetrenone having an X-ray powder diffraction pattern having a 2Θ value of 6.29±0.2°;11.63 soil 0.2 °;12.49±0.2°;13.94±0.2°;14.46 soil 0.2 °;14.78 soil 0.2 °;15.63±0.2°;17.05±0.2°;18.47±0.2°;18.81±0.2°;19.12±0.2°;19.50 + -0.2 °;20.08±0.2°;20.82±0.2°; 22.11+ -0.2 °;22.43±0.2°;23.21±0.2°;23.43±0.2°; 24.37+ -0.2 °;25.43 soil 0.2 °;26.34 earth 0.2 °;27.74 earth 0.2 °;28.07 soil 0.2 °;28.86 earth 0.2 °;30.09 soil 0.2 °;31.43±0.2°;32.03 + -0.2 °;32.75±0.2°;34.07 + -0.2 °;34.78±0.2°;36.86±0.2°;37.88 the earth has a diffraction peak at 0.2 °.

Through the technical scheme, the menatetrenone crystal form I is a newly discovered brand new crystal form of menatetrenone, and the crystal form is thermodynamically stable; the 2 theta value is 11.63 degrees and 0.2 degrees; 14.78 soil 0.2 °;18.47±0.2°;20.08±0.2°; 22.11+ -0.2 °;23.43±0.2°; 24.37+ -0.2 °;26.34 earth 0.2 °;28.07 soil 0.2 °;28.86 earth 0.2 °;31.43±0.2°;32.03 + -0.2 °;32.75±0.2°;34.07 + -0.2 °; the diffraction peak at 36.86+/-0.2 degrees is different from that at the crystal form of the prior art menatetrenone, namely the new thermodynamically stable crystal form.

Further, the specific synthetic route is as follows:

the tetraene menadione used for preparing the tetraene menadione crystal form I is prepared by taking geranyl linalool, dicyclopentadiene and menadione as starting materials and carrying out bromination, depolymerization, cycloaddition, substitution and ring opening reaction. The reaction type is simple, the process is easy to control, the intermediate quality is better, and the purity and the yield of the finished product of the menatetrenone are high. Compared with the existing synthesis method, the synthesis method has the advantages of low cost of starting materials, no production potential safety hazard caused by metal catalytic reaction, mild and controllable reaction conditions, simple synthesis steps, good product crystal form state, high overall reaction yield of more than 40 percent and suitability for industrial production.

In addition, a method for preparing the menatetrenone crystal form I is provided, which comprises the following steps:

1) Preparing liquid; dissolving the crude menatetrenone in a mixed solvent of an organic solvent 1 and an organic solvent 2, and stirring at a temperature of 40-60 ℃ until the menatetrenone is dissolved;

2) Crystallization; cooling the mixed solution obtained in the step 1) to-10-0 ℃ to precipitate crystals; stirring the reaction solution, and filtering to obtain a filter cake;

3) And (3) leaching the filter cake obtained in the step (2) by using an organic solvent 2, and drying the filter cake for 8 hours at 20-25 ℃ under vacuum to obtain the tetraene menadione crystal form I.

According to the technical scheme, the obtained menatetrenone is a brand new crystal form, and compared with the menatetrenone crystal form prepared by the prior art, the menatetrenone crystal form has obvious difference on an XRPD spectrogram. Compared with the tetraenaquinone crystal form prepared by the prior art, the new tetraenaquinone crystal form has obvious advantages in terms of the physical form of crystal nodules and particle size; the concrete steps are as follows: the solid form is better, the dispersibility is better, the fluidity is better, and the crystal form stability is better.

In step 3), the organic solvent 2 for washing is one of methanol, ethanol, isopropanol, and n-butanol, and more preferably ethanol; the mass-volume ratio of the menatetrenone to the organic solvent 2 is 1:6-1:12, and more preferably 1:8.

Further, in step 1), the organic solvent 1 is one of n-heptane, petroleum ether, n-hexane and n-pentane.

By comparison of crystallization experiments under different solvents, the dissolution rate is fastest under an n-heptane system, and the uniformity of the system is optimal; preferably n-heptane;

further, in step 1), the organic solvent 2 is one of methanol, ethanol, isopropanol, and n-butanol.

Compared with crystallization experiments under different solvents, the yield of the precipitated product under an ethanol system is the maximum, so that ethanol is further preferred;

further, in the step 1), the mass-volume ratio of the crude menatetrenone to the organic solvent is 1:3-5.

Through a mass-volume ratio experiment of mixing the screened crude product and the organic solvent 1, when the volume ratio is 1:4, the crystallization yield of the system and the state of the product are optimal, so that the ratio is more preferably 1:4;

further, in the step 1), the mass-volume ratio of the crude menatetrenone to the organic solvent is 1:4-10.

Through a mass-volume ratio experiment of mixing the screened crude product and the organic solvent 2, when the volume ratio is 1:6, the crystallization yield of the system and the state of the product are optimal, so that the ratio is more preferably 1:6;

further, in step 1), the crystallization time is 2 to 10 hours.

Through screening the crystallization time, when the crystallization time is less than 4 hours, the crystallization yield is lower, and when the crystallization time is more than 4 hours, impurities are easy to wrap, so the crystallization time is preferably 4 hours.

The invention has the beneficial effects that: the menatetrenone crystal form I has good stability and small particle size; the preparation method of the menatetrenone crystal form I is simple and convenient to operate, high in yield and low in cost, and is suitable for industrial production.

Drawings

FIG. 1 is an X-ray diffraction (X-PRD) pattern of crystalline form I of menatetrenone according to example 4 of the present invention;

FIG. 2 is a Differential Scanning Calorimetry (DSC) and thermogravimetric analysis (TGA) profile of crystalline form I of menatetrenone according to example 4 of the present invention.

FIG. 3 is an infrared spectrum of crystalline form I of menatetrenone according to example 4 of the present invention

FIG. 4 shows nuclear magnetic resonance hydrogen spectrum (1H-NMR) of menatetrenone according to example 4 of the invention

FIG. 5 shows nuclear magnetic resonance carbon spectrum (13C-NMR) of menatetrenone according to example 4 of the invention

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described in the following in conjunction with the embodiments of the present invention, and it is obvious that the described embodiments are only some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.

The specific conditions are not noted in the examples and are carried out according to conventional conditions or conditions recommended by the manufacturer. The reagents or apparatus used were conventional products commercially available without the manufacturer's attention.

The testing instrument is Bruker AV 400 type nuclear magnetic resonance apparatus, and the hazardous agent is DMS0-t/6 DEG

Infrared detection instrument: bruker Tensor 27 Infrared spectrometer. Conditions are as follows: potassium bromide tabletting method.

X-ray diffraction instrument: panalytical X' Pert PRO; conditions are as follows: cu target, 40KV and 40mA target.

Differential thermal/thermogravimetric analysis (DSC/TG) instrument: NETZSCH STA 409PC/PG; conditions are as follows: 30/10.0 (K/min)/310.

Example 1

To a 100ml glass reaction flask, 2g of crude menatetrenone and 12ml of ethanol were added in sequence, and the solution was stirred at 50 ℃. Then the system is cooled to 0-10 ℃, and the system is stirred for 4 hours after solid precipitation. The mixture was filtered, and the filter cake was rinsed with 6ml of absolute ethanol. And (3) vacuum drying the filter cake at 20-25 ℃ for 8 hours to obtain pale yellow crystalline powder.

The synthesized menatetrenone is subjected to nuclear magnetic resonance hydrogen spectrum ¹ H-NMR and nuclear magnetic resonance carbon spectrum ¹³ C-NMR) confirms that the chemical structure is consistent with that of FIG. 4 and FIG. 5, the nuclear magnetic spectrum of the sample is clear in cleavage, and the sample quality is better (see FIG. 3 and FIG. 4).

The obtained menatetrenone sample was heated to 37.1 ℃ to begin an endothermic peak and heated to 39.6 ℃ to begin an exothermic peak, and the analysis chart of the differential scanning calorimetry was basically consistent with that of FIG. 2, and the coincidence degree was high.

The resulting menatetrenone sample had a weight loss of about 10.3% when heated to 278.6 ℃, the thermogravimetric analysis substantially in accordance with figure 2.

The prepared menatetrenone sample is subjected to infrared spectrum scanning, and the infrared spectrum characteristic absorption is as follows: 2963cm ^-1 ，2911cm ^-1 ，2851cm ^-1 、1448cm ^-1 ，1383cm ^-1 cm、1660cm ^-1 1618cm ^-1 ，1594cm ^-1 . The infrared spectrogram is basically consistent with the figure 3, and is consistent with the structural characteristics of the product.

Example 2

To a 100ml glass reaction flask, 2g of crude menatetrenone and 12ml of methanol were added in sequence, and the solution was stirred at 50 ℃. Then the system is cooled to 0-10 ℃, and the system is stirred for 4 hours after solid precipitation. The mixture was filtered and the filter cake was rinsed with 6ml of absolute ethyl=methanol. And (3) vacuum drying the filter cake at 20-25 ℃ for 8 hours to obtain pale yellow crystalline powder.

Example 3

To a 100ml glass reaction flask, 2g of crude menatetrenone and 8ml of n-heptane were added in sequence, and the solution was stirred at 50 ℃. Then the system is cooled to room temperature, 16ml of ethanol is added dropwise into the system, the system is cooled to 0-10 ℃ and the precipitated solid is stirred for 4 hours. The mixture was filtered, and the filter cake was rinsed with 6ml of absolute ethanol. And (3) vacuum drying the filter cake at 20-25 ℃ for 8 hours to obtain pale yellow crystalline powder.

Example 4

To a 100ml glass reaction flask, 2g of crude menatetrenone and 8ml of n-heptane were added in sequence, and the solution was stirred at 50 ℃. Then the system is cooled to room temperature, 16ml of methanol is added dropwise into the system, the system is cooled to 0-10 ℃ and the precipitated solid is stirred for 4 hours. The mixture was filtered and the filter cake was rinsed with 6ml of anhydrous methanol. And (3) vacuum drying the filter cake at 20-25 ℃ for 8 hours to obtain pale yellow crystalline powder.

The synthesized menatetrenone is subjected to nuclear magnetic resonance hydrogen spectrum ¹ H-NMR and nuclear magnetic resonance carbon spectrum ¹³ C-NMR) confirm that the chemical structure is consistent with FIGS. 4 and 5, and the sample is nuclear magnetic resonanceThe spectrum is clear in split, and the sample quality is better (see figures 3 and 4).

Effect examples

The diffraction peaks of the crystalline form of the menatetrenone sample prepared according to the present invention have the following obvious characteristics: the X-ray powder diffraction diagram is 6.29+/-0.2 degrees at the 2 theta value; 11.63 soil 0.2 °;12.49±0.2°;13.94±0.2°;14.46 soil 0.2 °;14.78 soil 0.2 °;15.63±0.2°;17.05±0.2°;18.47±0.2°;18.81±0.2°;19.12±0.2°;19.50 + -0.2 °;20.08±0.2°;20.82±0.2°; 22.11+ -0.2 °;22.43±0.2°;23.21±0.2°;23.43±0.2°; 24.37+ -0.2 °;25.43 soil 0.2 °;26.34 earth 0.2 °;27.74 earth 0.2 °;28.07 soil 0.2 °;28.86 earth 0.2 °;30.09 soil 0.2 °;31.43±0.2°;32.03 + -0.2 °;32.75±0.2°;34.07 + -0.2 °;34.78±0.2°;36.86±0.2°;37.88 soil 0.2 °;

the results are analyzed as follows, in conjunction with fig. 1-5: FIG. 1 is an X-ray diffraction (X-PRD) pattern of menatetrenone form I; as can be seen from fig. 1, the X-ray powder diffraction result of the sample shows that it is crystalline powder.

Fig. 2: differential Scanning Calorimetry (DSC) and thermogravimetric analysis (TGA) profiles of menatetrenone form I; as can be seen from fig. 2, DSC/TG analysis of the samples indicated that the samples exhibited endothermic peak melting at 37.1 ℃ to 39.6 ℃ followed by a sustained exotherm to about 200 ℃ with significant weight loss, possibly with sublimation or decomposition of the samples.

Fig. 3: infrared spectrogram of menatetrenone crystal form I; as can be seen from figure 3 of the drawings,

a.2963，2911，2851cm ^-1 ：CH ₂ ，CH ₃ C-H stretching vibration of 1448, 1383cm ^-1 ：

CH ₂ ，CH ₃ Bending vibration of C-H in the molecule, indicating that CH is contained in the molecule ₂ ，CH ₃ 。

b.1660cm ^-1 : the stretching vibration of the ketocarbonyl group c=o indicates that the molecular structure contains the ketocarbonyl group. c.1618 1594cm ^-1 : c=c stretching vibration of benzene ring skeleton and olefinic bond, 795, 720cm ^-1 : ortho-substituted benzene ring and olefinic bond = C-H flexural vibration, proving that there are ortho-substituted benzene ring and olefinic bond in the molecule.

As can be seen from infrared spectrum, the sample contains ortho-substituted benzene ring, olefinic bond and CH ₂ 、CH ₃ And ketocarbonyl groups, and the like, and are consistent with the structure of the menatetrenone.

Fig. 4: menatetrenone nuclear magnetic resonance hydrogen spectroscopy (1H-NMR); as can be seen from the figure 4 of the drawings, ¹ h NMR spectra gave 11 sets of peaks with an integral ratio (from low to high) of 2:2:4:1:3:6:6:3:3:3:6 for a total of 40 protons, consistent with the number of protons in the menaquinone molecular structure. In combination with the H-HCOSY (FIG. 4) spectrum, the individual ascribed spectral peaks are as follows:

a. the multiple peaks of delta 8.0901-8.0628 (m, 2H) ppm are equivalent to 2 protons, the combined chemical shift value and peak assignment are H-6 and H-9 in the molecule, and the multiple peaks of delta 7.7052-7.6599 (m, 2H) ppm which are related to the coupling of the H-H COSY spectrum are H-7 and H-8, which form ortho-substituted phenyl groups in the molecule.

b. The multiple peaks of delta 5.1006-4.9997 (m, 4H) ppm are equivalent to 4 protons, the combined chemical shift value belongs to four olefinic protons of H-13, H-17, H-21 and H-25 in the molecule, the double peaks of delta 3.3793-3.3620 (d, 2H) ppm related to coupling on the H-H COSY spectrum belong to H-12 in the molecule, and the multiple peaks of delta 2.0762-2.0103 (m, 6H) ppm can be sequentially attributed to H-16, H-20, H-24, delta 1.9911-1.9041 (m, 6H) ppm are H-15, H-19 and H-23; the broad peak of delta 1.7948 (br, 3H) ppm is H-27, and the multiple peaks of delta 1.5625-1.5594 (m, 6H) are H-28 and H-29; the multiple peak of delta 1.6693-1.6671 (m, 3H) ppm is H-31, the broad peak of delta 1.5896 (br, 3H) ppm is H-30, which constitute multiple isoprenoid groups in the molecule.

c. The single peak of delta 2.1881 (s, 3H) ppm corresponds to 3 protons, and the binding chemical shift value is attributed to H-11 methyl in the molecule.

¹ H NMR shows that the molecule contains 1 ortho-substituted phenyl group, a plurality of isoprenoid groups and 1 methyl, which are consistent with the structure of tetraenaphthaquinone.

Fig. 5: menatetrenone nuclear magnetic resonance carbon spectrum (13C-NMR); as can be seen from figure 5 of the drawings, ¹³ the C NMR spectrum had 31 peaks corresponding to 31 carbons in the molecule, and from HSQC, 21 hydrogen-carbon peaks were observed in the molecule. From the dept135 and dept90 spectra, peaks with chemical shifts of δ 185.4519, 184.5108, 146.1566, 143.3492, 137.5517, 135.2013, 134.8833, 132.1869, 132.1497, and 131.2382ppm were quaternary carbons (10 peaks), peaks with δ 133.3248, 133.2678, 126.3075, 126.1928, 124.4028, 124.1615, 123.8711, 119.0846ppm were tertiary carbons (8 groups of peaks), peaks with δ 39.7249, 39.7128, 39.6630, 26.7559, 26.6153, 26.4917, and 26.0110ppm were secondary carbons (7 peaks), and peaks with δ 25.6966, 17.6838, 16.4294, 16.0269, 15.9706, and 12.6816ppm were primary carbons (6 peaks). In combination with H-H COSY (FIG. 4), HSQC, HMBC spectra, the respective ascribed spectral peaks are as follows:

a. delta 185.4519 (quaternary C), 143.3492 (quaternary C), 146.1566 (quaternary C), 184.5108 (quaternary C), 132.1869 (quaternary C), 126.3075 (tertiary C), 133.3248 (tertiary C), 133.2678 (tertiary C), 126.1928 (tertiary C), 132.1497 (quaternary C), 12.6816 (tertiary C) ppm: the correlation relations on the HSQC and HMBC spectra are respectively C-1-C-11 in the molecule, and the C-1-C-11 and the HMBC constitute 2-methyl-3-naphthalene-1, 4-dione groups in the molecule.

b. Delta 26.0110 (secondary C), 119.0846 (tertiary C), 137.5517 (quaternary C), 16.4294 (primary C) ppm: the correlation relations on the HSQC and HMBC spectra are respectively assigned to C-12, C-13, C-14, C-15 and C-27 in the molecule, and the C-13, C-14, C-15 and C-27 form isoprenoid substrate segments in the molecule. Similarly δ 39.7249 (secondary C), δ 26.4917 (secondary C), 124.4028 (tertiary C), 135.2013 (quaternary C), 16.0269 (primary C) ppm: the correlation relations on the HSQC and HMBC spectra are respectively attributed to C-15, C-16, C-17, C-18 and C-28 in the molecule; delta 39.7128 (sec), delta 26.6153 (sec), 124.1615 (tert-C), 134.8833 (quaternary C), 15.9706 (tert-C) ppm: the correlation relations on the HSQC and HMBC spectra are respectively attributed to C-19, C-20, C-21, C-22 and C-29 in the molecule; delta 39.6630 (secondary C), delta 26.7559 (secondary C), 123.8711 (tertiary C), 131.2382 (quaternary C), 17.6838 (primary C), 25.6966 (primary C) ppm: the correlation relations on the HSQC and HMBC spectra are respectively assigned to C-23, C-24, C-26, C-30 and C-31 in the molecule, and the C-24, C-26, C-30 and C-31 jointly form a plurality of isoprenoid substrate segments in the molecule.

From the slave ¹³ The C NMR spectrum shows that the molecular structure contains 1 2-methyl-3-naphthalene-1, 4-dione groups and a plurality of isoprenoid substrate segments, which are consistent with the structure of the menatetrenone.

Therefore, the invention is a novel crystal form of menatetrenone, and the crystal form is thermodynamically stable; the 2 theta value is 11.63 degrees and 0.2 degrees; 14.78 soil 0.2 °;18.47±0.2°;20.08±0.2°; 22.11+ -0.2 °;23.43±0.2°; 24.37+ -0.2 °;26.34 earth 0.2 °;28.07 soil 0.2 °;28.86 earth 0.2 °;31.43±0.2°;32.03 + -0.2 °;32.75±0.2°;34.07 + -0.2 °; the diffraction peak value at the position of 36.86+/-0.2 degrees is different from that at the position of the existing menatetrenone crystal form, and the obvious difference exists, so that the obtained crystal form I has the characteristics of good thermal stability, good solid form and good solid dispersion. Compared with the prior art, the method has the obvious advantages that in the preparation process of the crystal form, the optimal conditions are screened out by each parameter of crystallization; the solvent type, the solvent volume, the crystallization temperature and the crystallization time are fully verified; the parameters of crystallization are precisely controlled, so that the menatetrenone sample prepared according to the invention has stable crystal form, high crystallinity and good solid form.

Finally, it should be noted that: the foregoing description is only illustrative of the preferred embodiments of the present invention, and although the present invention has been described in detail with reference to the foregoing embodiments, it will be apparent to those skilled in the art that modifications may be made to the embodiments described, or equivalents may be substituted for elements thereof, and any modifications, equivalents, improvements or changes may be made without departing from the spirit and principles of the present invention.

Claims

1. A crystalline form I of menatetrenone, characterized in that the X-ray powder diffraction pattern of form I is 6.29±0.2° at a 2Θ value; 11.63 soil 0.2 °;12.49±0.2°;13.94±0.2°;14.46 soil 0.2 °;14.78 soil 0.2 °;15.63±0.2°;17.05±0.2°;18.47±0.2°;18.81±0.2°;19.12±0.2°;19.50 + -0.2 °;20.08±0.2°;20.82±0.2°; 22.11+ -0.2 °;22.43±0.2°;23.21±0.2°;23.43±0.2°; 24.37+ -0.2 °;25.43 soil 0.2 °;26.34 earth 0.2 °;27.74 earth 0.2 °;28.07 soil 0.2 °;28.86 earth 0.2 °;30.09 soil 0.2 °;31.43±0.2°;32.03 + -0.2 °;32.75±0.2°;34.07 + -0.2 °;34.78±0.2°;36.86±0.2°;37.88 the earth has a diffraction peak at 0.2 °.

2. The crystalline form I of menatetrenone according to claim 1, characterized by the specific synthetic route as follows:

3. a process for the preparation of the crystalline form I of menatetrenone according to claim 1 or 2, characterized by the following steps:

1) Preparing liquid; dissolving the crude product of menatetrenone in a mixed solvent of an organic solvent 1 and an organic solvent 2,

stirring at 40-60deg.C until the solution is clear;

3) Leaching the filter cake obtained in the step 2) by using an organic solvent, and drying the filter cake for 8 hours at 20-25 ℃ under vacuum to obtain the tetraene menadione crystal form I.

4. A process for the preparation of menatetrenone form I according to claim 3, characterized in that in step 1) the organic solvent 1 is one of n-heptane, petroleum ether, n-hexane, n-pentane.

5. A process for the preparation of menatetrenone form I according to claim 3, characterized in that in step 1) the organic solvent 2 is one of methanol, ethanol, isopropanol, n-butanol.

6. A process for the preparation of crystalline form I of menatetrenone according to claim 3, characterized in that in step 1) the crude menatetrenone is mixed with organic solvent 1 in a mass to volume ratio of 1:3-5.

7. A process for the preparation of crystalline form I of menatetrenone according to claim 3, characterized in that in step 1) the crude menatetrenone is mixed with organic solvent 2 in a mass to volume ratio of 1:4-10.

8. A process for the preparation of menatetrenone form I according to claim 3, characterized in that in step 1) the crystallization time is 2-10h.