JPS6023362A - Preparation of dl-cysteine of single crystal - Google Patents

Abstract

PURPOSE:To obtain the titled compound useful as an addition agent for foods in good shelf stability, by using a hydrous lower alcohol as a solvent, neutralizing DL-cysteine hydrochloride with a base. CONSTITUTION:DL-Cysteine hydrochloride is neutralized with a base in a hydrous lower alcohol, to give DL-cysteine of single crystal. Ethylamine, diethylamine, triethylamine, etc. or lithium hydroxide may be cited as the base used in the method. An alcohol miscible with water, such as methanol, ethanol, etc. may be used as the hydrous lower alcohol. The degree of hydrous state is >=5wt%, usually 5-60%, preferably 10-50wt%.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing single crystalline DTJ-cysteine.

More specifically, one feature is that 4-cystine hydrochloride is neutralized with a base in a water-containing lower alcohol. 1
1 is a method for producing crystalline DT, +-cysteine.

Cysteine is a type of sulfur-containing amino acid and is a compound that has a wide range of uses such as food additives, permanent fluids, and pharmaceutical raw materials.

Generally, it is well known that cysteine is easily oxidized to cysteine by oxygen in the air.

In particular, 1) L-cysteine has conventionally been known to have no crystalline form and is an amorphous powder.
Because of their large size, they are susceptible to oxidation during storage and suffer from poor storage stability. Therefore, at present, it is mostly used in the form of hydrochloride monohydrate to improve stability1. However, when using this hydrochloride monohydrate, A base is required to neutralize 1 mole of hydrochloric acid. Therefore, there is no need to adjust the pH when using it, and it has good storage stability.
It has been desired to develop a method for producing TJ-cysteine.

Free f4ff DT, -7 The production method of stain i~ is DL=cysteine hydrochloric acid J? H1*U: p-) A method is known in which luenesulfonate is dissolved in methanol and neutralized with triethylamine, but DL-cysteine obtained by this method is amorphous and has drawbacks such as storage stability. is not resolved.

In view of these circumstances, the present inventors have conducted extensive studies on a method for producing free DL-cysteine with crystalline form ↑ and good storage stability. It was discovered that single-crystal free DL-cysteine having a scale-like or short needle-like crystal form can be obtained by suspending or dissolving it in a water-containing lower alcohol and neutralizing it with a base. The invention was completed.

That is, the method of the present invention is characterized in that DL-cysteine hydrochloride is neutralized using a water-containing lower alcohol as a solvent. - cysteine, thus monocrystalline DL-cysteine is obtained, which is characterized by the following X-ray diffraction spectrum:

Interstitial distance (X) Relative intensity * (I) 11.9Of 597 f 397 f 2.98 ff The old relative intensity (1) is based on the following arbitrarily set standard ff
-Very strong, f-Strong single crystalline DL-cysteine can be obtained by the method of the present invention11, which could not be foreseen from the prior art3, 4.The method of the present invention allows iVi
l~III T) TJ-cysteine is a scale-like crystalline substance (i), so it is a conventional problem and 7Iζ nursery stability is significantly 1~1~1~. I'm now seven years old.

J) TJ-cysteine salt used in the method of the invention
Shunji U1, anhydrous or 1 permanent can be used.
) 1-cysteine hydrochloride was mixed with the base and 1. If the solvent produces a salt that is soluble in water-containing lower alcohol, there are particular restrictions. ＾ group←i is not preferable because separation with precipitated free DL-cysteine becomes difficult at 11°.

Examples of the bases used include ethylamine, diethylamine, triethylamine, monoethanolam, thorium hydroxide, potassium hydroxide, alkali metal hydroxides or alkaline earth metal hydroxides such as calcium hydroxide or barium hydroxide. , lithium carbonate, thorium carbonate,
Examples include carbonates of alkali metals or alkaline earth metals such as potassium carbonate, calcium carbonate, or barium carbonate, or ammonia.

The process of the invention is carried out in a hydrous lower alcohol. The lower alcohols used are water-miscible alcohols such as methanol, ethanol, rhogropanol, isopropanol, tertiary butanol, cellosolve or methyl cellosolve.

In the method of the present invention, it is necessary for these alcohols to contain water, and the degree of water content is determined by the quintet.
There is no particular upper limit on the upper limit, but if the amount of water is too large, the recovery rate of DL-cysteine will decrease, so it is usually in the range of 5 to 60% by weight, preferably 10 to 50% by weight. . When the amount of water is less than 5 times, the obtained free NtDL-cysteine does not have a crystalline form and becomes amorphous, and has a quality with poor storage stability.

Although there are no particular restrictions on the use of hydrous lower alcohols, -l/ζ is usually 1, Dl', -7 for stein hydrochloride due to the recovery rate of DT, -cysteine. 1 to 20 cities 1 edition - times, good luck 2 to
It is used in a range of 10 times more weight.

The method of the present invention involves dissolving or suspending DL-cysteine hydrochloride in a water-containing lower alcohol and heating at -20 to 80°C, preferably
Neutralize by dropping, adding or blowing a base at a temperature of ~60° C. to precipitate free DL-cysteine. After neutralization, if necessary, cool and precipitate free u'lt,
DT, - separate cysteine by r. Neutralization is preferably carried out in an inert gas atmosphere such as nitrogen or argon in order to prevent the oxidation of the stain to cystine. In this way, 1) lfDT, -cysteine, which has a scale-like or needle-like crystal form and has good storage stability, is obtained.

Hereinafter, the present invention will be explained in detail with reference to Examples.

Example 1 DL in 24 omes of methanol containing 10 parts by weight of water
- Add and dissolve cysteine hydrochloride monohydrate 5271) 11
make me cum 3 at 20-25°C with stirring under nitrogen atmosphere.
Neutralization was achieved by adding 0.3 i/ml of triethylamine over a period of approximately 20 minutes. One analysis after stirring at the same temperature for 1 hour.
By washing the crystals with methanol and vacuum drying them, a colorless dagger-like product is obtained (TJ)
- Obtained cysteine.

Collection-F? + 6517 purity 100chi obtained here,
X-ray diffraction spectrum of crystal of tDL-cysteine (Ct)
+: λ- using Ni 25KV 14 mA power supply
1,5418 shows the following X-ray diffraction pattern.

Interstitial distance (X) Relative strength (1) 11.90 0.66 5.97 0.33 4.55 0.03 4.20 0.07 697 09 682 0.06 3.79 0.12 3 .75 0.04 671 0.05 U41 00ro3.18 0.05 608 0.05 2.98 1.00 2.68 0.01 260 0.01 2.52 0.03 Example 2 Actual h111 In Example 1, water-containing methanol was mixed with 40 parts of water (
Water-containing isog containing W % 2-nor 240rn/
+, also add l-ethylamine) /ノ23.7
? Same as Example 1 except for replacing with (31.525 g of colorless)
1llllD'[+ -Cystine is obtained. As a result of purity analysis by high performance liquid chromatography, it was found to be 41t11oo% pure and free of cystine. A) The X-ray diffraction pattern of the obtained crystal was exactly the same as that of Example 1.

Example Roki J/11 In Example 1, triethylamine was replaced with 1857 aqueous ammonia, except for the same procedure as in Example 1.
-1 Sistine! J. The purity was in terms of kHz, and the X-ray diffraction pattern of the crystal was exactly the same as in Example 1.

Example 4 200 m of methanol containing 20 weight iit;% of water
l! Inside D T, - 1 water 10 things for cysdine hydrochloric acid 527
Add 7 and suspend. Under nitrogen atmosphere, +(/, l'
Lithium hydroxide 1267 was gradually added at 20 to 25° C. to neutralize the mixture, and the mixture was stirred at the same temperature for 1 hour. The precipitated products were taken from door to door, washed with methanol, and then vacuum dried to obtain colorless, scaly products of iGoriDL-cysteine.

Yield: 32.7 y (recovery rate: 90), purity: 100
It's %. The X-ray diffraction pattern of the shredded crystal was the same as in Example 1.

Comparative Example: 176 g of DL-cystine hydrochloride monohydrate was added and dissolved in 80'+πe of methanol. Under nitrogen atmosphere,
While stirring at 20-25° C., triethylamine 1017 was added dropwise to neutralize the mixture. After stirring at the same temperature for 1 hour, the precipitate that had precipitated was washed with methanol and vacuum dried to form a colorless powder.
Got Sistine. The yield was 1t5S'.

Reference Example The free DT,-cysteine obtained in Example 1 and Comparative Example was placed in a glass crystallization dish and left in a normal room to examine its storage stability/ζ0. The results are shown in Table 1.

Table-1 Sample Cystine production l (wt%) after 30 days Karimi is 1; Example 10 Comparative example 5 4 patent applicants Mitsui Toatsu Higaku Co., Ltd. 0

Claims (1)

[Claims] ]') A crystalline DT characterized by neutralizing TJ-cystine hydrochloride with a base in a water-containing lower alcohol.
+-Production method of cysteine.