JP2915516B2 - Production method of O-methylisourea sulfate - Google Patents

Description

The present invention relates to a novel process for producing O-methylisourea sulfate, which is useful as an intermediate for pharmaceuticals, agricultural chemicals and industrial chemicals.
More specifically, the present invention relates to a process for producing O-methylisourea (hereinafter sometimes abbreviated as OMIU) sulfate, which comprises reacting O-methylisourea hydrogen sulfate with an alkaline compound in a liquid medium containing methanol.

[Conventional technology]

Conventionally, several methods have been proposed for the production of OMIU sulfate.

For example, in "Biochimica et Biophysica Acta", Vol. 18, 1955, p. 448, concentrated sulfuric acid (0.125 mol) is added to an ice-cold aqueous solution of crystalline cyanamide (0.25 mol) in anhydrous methanol to remove a small amount of insoluble matter. It is described that crystals of OMIU sulfate were obtained by removing the mixture by filtration and leaving it at room temperature for 4 days.

However, in the method proposed above, the reaction rate is extremely slow such that the reaction requires 4 days at room temperature, and the yield of OMIU sulfate relative to cyanamide is 44%, which is quite insufficient. It could not be adopted as a manufacturing method.

Further, U.S. Pat.No. 3,931,316 discloses that substantially equimolar amounts of cyanamide and OMIU hydrogen sulfate are mixed in a liquid medium containing methanol as an essential component.
A method for preparing OMIU sulfate is disclosed, which comprises maintaining at 5-40 ° C. for the time required for sulfate formation.

This process is essentially a two-step reaction of producing OMIU sulfate by reacting OMIU bisulfate produced according to the known reaction formula with cyanamide as in the reaction formula in a liquid medium containing methanol. Consisting of

However, even in the second proposal, the reaction speed of the second stage is slow, so that the reaction time is considerably long, and the total reaction yield from cyanamide is not sufficiently satisfactory. Therefore, in this second proposal, the first stage and the second stage
It is recommended to increase the production yield of OMIU hydrogen sulfate and OMIU sulfate by recycling the mother liquor after separation of OMIU hydrogen sulfate and OMIU sulfate in the stage.
Further, this proposal also assumes the use of crystalline cyanamide, which is complicated and dangerous to produce, and if an aqueous cyanamide solution having a concentration of, for example, 50% by weight is used, the above-mentioned reaction in the second stage is particularly difficult. There is a problem that the reaction of the formula does not proceed, and instead, the urea generation reaction as shown in the following reaction formula has priority.

[Problems to be Solved by the Invention] The present inventors have studied to solve the above-mentioned problems of the prior art and to obtain OMIU sulfate with high purity and high yield in a relatively short reaction time. As a result, for example, OMIU hydrogen sulfate is produced by reacting cyanamide with a substantially equimolar amount of concentrated sulfuric acid in a methanol-containing solution,
Then, by reacting an alkaline compound such as calcium carbonate with a methanol-containing solution of the OMIU hydrogen sulfate, it is found that the intended purpose can be achieved, and a crystal having the above problem as cyanamide is obtained. The present inventors have found that the desired OMIU sulfate can be produced in a considerably high yield even when a cyanamide aqueous solution having a concentration of, for example, 50% by weight is used without using cyanamide, and the present invention has been completed.

[Means for solving the problem]

The present invention relates to a process for producing O-methylisourea sulfate, which comprises the following steps A and B: A. O-methylisourea sulfate; An alkaline compound is reacted in a methanol-containing liquid medium to provide a process for producing O-methylisourea sulfate.

 Hereinafter, the present invention will be described in detail.

O-methylisourea (OMI) used in the method of the present invention
U) The hydrogen sulfate (A) is not particularly limited. For example, a solution of OMIU hydrogen sulfate obtained by reacting cyanamide and sulfuric acid in a methanol-containing solvent is particularly preferably used. Used. Next, this reaction will be described.

OMIU hydrogen sulfate production reaction step The reaction in this step proceeds in the same manner as in the above reaction formula.

When crystalline cyanamide is used as the above cyanamide,
It is the highest in terms of total yield of OMIU sulfate production.
However, the method of the present invention is not necessarily limited to the use of crystalline cyanamide as cyanamide, for example,
Carbon dioxide gas is blown into a methanol solution of cyanamide by the method described in JP-A-2-64009, that is, a methanol dispersion of lime nitrogen, as shown in the following reaction formula, and solid by-products are removed by filtration. The methanol solution of cyanamide thus obtained can be concentrated and used as needed.

Further, as a result of the study by the present inventors, even when an aqueous solution of cyanamide according to a conventional method is used, for example, in the presence of a large amount of methanol such as 3 mol or more per 1 mol of cyanamide,
It has been found that the O-methylation reaction of the above reaction formula has priority over the urea generation reaction of the above reaction formula, and that the production of urea is unexpectedly low, and it is possible to use a 40 to 60% by weight aqueous solution of cyanamide. Turned out to be.

Generally, concentrated sulfuric acid having a concentration of 95% by weight or more is preferably used as the sulfuric acid. The amount of sulfuric acid used is preferably 1.0 to 1.2 mol per 1 mol of cyanamide.

From the viewpoint of suppressing the urea production reaction, the amount of methanol used is 2 to 10 mol, particularly 3 to
Preferably it is 8 moles.

Examples of the reaction method in this step include (a) a method of adding crystalline cyanamide or a cyanamide solution to a mixed solution of concentrated sulfuric acid and methanol, and (b) a method of adding concentrated sulfuric acid to a methanol-containing solution of cyanamide. As an example, the method (a) requires a reaction under a low temperature condition of, for example, 5 ° C. or lower in order to suppress a side reaction between sulfuric acid and methanol (a reaction for producing monomethyl sulfuric acid). Since there is a problem, it is preferable to adopt the method (b).

According to the above method (b), the reaction temperature is generally 30 ° C. or lower, preferably 5 to 20 ° C., and the reaction time is about 2 to 12 hours, although it cannot be unequivocally determined by the scale of the reaction.

The reaction product of this reaction step has a form of a solution of OMIU bisulfate in a methanol-containing solvent or a slurry of the solvent containing undissolved crystals of the bisulfate. In order to suitably use this reaction product as the solution of the OMIU bisulfate (A) of the present invention, an appropriate amount of the OMIU sulfate is sufficient to dissolve the OMIU sulfate formed in the next reaction step. Of water is added to make a homogeneous solution.

In the method of the present invention, the OMIU obtained as described above is used.
The desired product OMIU sulfate is produced by reacting the hydrogen sulfate (A) and about 1 equivalent of the alkaline compound (B) with the OMIU hydrogen sulfate in a liquid medium. Next, this reaction will be described.

OMIU sulfate production reaction step In this reaction step, as the solution of OMIU hydrogen sulfate (A), use of the methanol-containing solution of the OMIU hydrogen sulfate obtained in the OMIU hydrogen sulfate production reaction step is preferable.

Examples of the alkaline compound (B) include carbonates, hydroxides and oxides of alkaline earth metals such as calcium carbonate and calcium hydroxide. Of these, use of calcium carbonate or calcium hydroxide is preferable, and use of calcium carbonate is particularly preferable, for reasons such as easy availability, handling, reaction operation, etc., and low cost.

The amount of the alkaline compound (B) used is about 1 equivalent relative to the OMIU hydrogen sulfate (A), that is, 0.95 to 0.95.
It must be 1.05 equivalents, preferably 0.99 to 1.01 equivalents.

In this step, the reaction when calcium hydroxide is used as the alkaline compound (B) is considered to follow the following reaction formula.

Although the reaction method in this step is not particularly limited, for example, powdered calcium carbonate, calcium hydroxide, or the like as an alkaline compound (B) in a methanol-containing solution of OMIU hydrogen sulfate (A) is used. Can be suitably employed. Therefore, the liquid medium in this case is a methanol-containing solvent in which the OMIU hydrogen sulfate is dissolved. As described above, the liquid medium in the method of the present invention may be a methanol-containing solvent in which OMIU hydrogen sulfate is dissolved, for example, a methanol-water mixed solvent.

With the addition of the powdered calcium carbonate or calcium hydroxide, a precipitate such as calcium sulfate precipitates.

The reaction temperature is generally 10 to 30 ° C, preferably 20 to 25 ° C, and the reaction time is generally about 3 to 6 hours.

After completion of the reaction, the formed precipitate was removed by filtration, and the obtained filtrate was concentrated under reduced pressure so that the concentration of OMIU sulfate was about 50% by weight.
Crystals of sulfate are precipitated, and the crystals are separated by filtration and dried to obtain crystals of OMIU sulfate, which is the object of the method of the present invention.

〔Example〕

 Hereinafter, the present invention will be described in more detail with reference to examples.

Example 1 A three-necked flask equipped with a 500 ml stirring device, a thermometer and a raw material charging device was charged with 128 g (about 4 mol) of methanol and 50 g of methanol.
84 g (about 1 mol) of a cyanamide aqueous solution having a concentration of 1% by weight was added and dissolved by stirring.
110 g (about 1.1 mol) of 98% by weight concentrated sulfuric acid was added dropwise over about 3 hours to react, thereby obtaining 322 g of a methanol-containing solution of OMIU hydrogen sulfate. This solution contained 0.85 mole of OMIU hydrogen sulfate (85% reaction yield) and 0.15 mole of urea.

(OMIU bisulfate concentration: 3.17 mol /) (2) OMIU sulfate production reaction 3 equipped with a stirrer, thermometer and raw material input device
322 g of the solution prepared in (1) (containing 0.85 mol of OMIU bisulfate and 0.25 mol of sulfuric acid) was placed in a two-necked flask, and 26 ml of water was further added.
Then, 110 g (approximately 1.1 mol) of calcium carbonate was added over about 3 hours under a condition of 20 to 25 ° C. while stirring, and the reaction was allowed to proceed. Wash with 94 g of water, and combine this washing solution and the filtrate with O
408 g of a water-methanol solution of MIU sulfate was obtained. (Contains 0.425 mol of OMIU sulfate) About 200 g of methanol and water are distilled off from this OMIU sulfate solution under a reduced pressure of 30 torr, and then 233 g of methanol is added thereto.
Was added to extract OMIU sulfate crystals, and the crystals were filtered off and dried to obtain 86 g of OMIU sulfate (99% by weight,
About 0.35 mol). The yield based on the starting cyanamide is
It was about 70%.

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Claims (1)

(57) [Claims] In a process for producing O-methylisourea sulfate, the following A and B, A. O-methylisourea hydrogen sulfate, and B. about 1 equivalent to 1 mol of the O-methylisourea hydrogen sulfate are used. A method for producing O-methylisourea sulfate, characterized by reacting an alkaline compound of formula (I) in a liquid medium containing methanol.