CN113004174A - Preparation of alkyl 2- (alkylcarbamoyl) hydrazine-1-carboxylates or their corresponding urazole salts - Google Patents

Preparation of alkyl 2- (alkylcarbamoyl) hydrazine-1-carboxylates or their corresponding urazole salts Download PDF

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CN113004174A
CN113004174A CN202011507935.0A CN202011507935A CN113004174A CN 113004174 A CN113004174 A CN 113004174A CN 202011507935 A CN202011507935 A CN 202011507935A CN 113004174 A CN113004174 A CN 113004174A
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毛鲁斯·马蒂
让·沙夫特资
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    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
    • C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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    • C07C281/00—Derivatives of carbonic acid containing functional groups covered by groups C07C269/00 - C07C279/00 in which at least one nitrogen atom of these functional groups is further bound to another nitrogen atom not being part of a nitro or nitroso group
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    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C281/00—Derivatives of carbonic acid containing functional groups covered by groups C07C269/00 - C07C279/00 in which at least one nitrogen atom of these functional groups is further bound to another nitrogen atom not being part of a nitro or nitroso group
    • C07C281/02—Compounds containing any of the groups, e.g. carbazates
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Abstract

The present invention relates to the preparation of alkyl 2- (alkylcarbamoyl) hydrazine-1-carboxylates or their corresponding urazole salts. The present invention relates to the preparation of alkyl 2- (alkylcarbamoyl) hydrazine-1-carboxylates or their corresponding derivatives alkyl-4H-1, 2, 4-triazole-3, 5-dialkoxides (urazole salts). This is particularly advantageous because a one-pot reaction is used and alkyl acetate is used as solvent in steps a) and b) of its synthesis.

Description

Preparation of alkyl 2- (alkylcarbamoyl) hydrazine-1-carboxylates or their corresponding urazole salts
Technical Field
The invention relates to a preparation method of 2- (alkyl carbamoyl) hydrazine-1-carboxylic acid alkyl ester or a corresponding derivative thereof, namely alkyl-4H-1, 2, 4-triazole-3, 5-diol salt compounds (urazole salt compounds).
Background
The 1,2, 4-triazoline-3, 5-diketone compound or the urazole compound can be synthesized by different routes respectively. Breton et al Tetrahedron Letters 55(2014),4661-4663 disclose on the one hand a reaction route for 1,2, 4-triazoline-3, 5-diones or urazole compounds which comprises the cyclization of semicarbazones which are synthesized from ethyl carbazate and alkyl isocyanates. In another aspect, alternative reaction pathways are disclosed. This reaction pathway involves the cyclization of a semicarbazide compound synthesized from arylhydrazine-ethyl 1,2-dicarboxylate in acetonitrile, wherein the arylhydrazine-ethyl 1,2-dicarboxylate is prepared from ethyl carbazate and aryl chloroformate in dichloromethane.
For the first option, the proposed procedure is disadvantageous, since alkyl isocyanates are highly toxic compounds.
In the second alternative, it is highly disadvantageous that two different solvents are used starting from ethyl carbazate to the synthesis of semicarbazide, and that the intermediate product (ethyl aryl hydrazine-1, 2-dicarboxylate-1, 2-dicarboxylates) needs to be isolated. The separation and use of different solvents increases labor costs, time costs, and post-processing costs. In particular, when different solvents are used, additional costs are incurred due to the occurrence of additional separation processes, such as for storage tanks, solvent recovery, and the loss of the desired product increases.
Disclosure of Invention
Therefore, the problem to be solved by the present invention is to provide a new, efficient and lean method for synthesizing semicarbazide compounds, urazole salt compounds, urazole compounds, or 1,2, 4-triazoline-3, 5-dione compounds, respectively.
Surprisingly, this problem can be solved by a process according to claim 1, wherein in step a) and step b) a one-pot reaction is carried out using the same solvent without isolation of the alkyl aryl hydrazine-1,2-dicarboxylate (1, 2-dicarboxylate) formed as intermediate.
It has also been found that the corresponding 1,2, 4-triazoline-3, 5-diones can be synthesized directly from the corresponding urazole-based compounds. This allows for further improvements in efficiency in the production process.
Further aspects of the invention are the subject matter of the further independent claims. Particularly preferred embodiments are the subject of the dependent claims.
Brief description of the drawings
Figure 1 schematically shows the reactions relevant to the present invention.
Detailed Description
In a first aspect, the present invention relates to a process for the manufacture of a compound of formula (I) in a one-pot reaction,
Figure BDA0002845443720000021
comprising the step a)
a) Reacting an alkyl hydrazine carboxylate of formula (II) with an aryl chloroformate to form an intermediate 1-alkyl 2-aryl hydrazine-1,2-dicarboxylate of formula (III)
Figure BDA0002845443720000022
Figure BDA0002845443720000031
Followed by step b)
b) Reacting the intermediate hydrazine-1, 2-dicarboxylic acid 1-alkyl 2-aryl ester of formula (III) with an alkylamine of formula (IV) to produce a compound of formula (I)
R1-NH2 (IV)
It is characterized in that
The reaction of step a) and step b) is of formula CH3COOR' in an alkyl acetate solvent;
and is
The intermediate hydrazine-1, 2-dicarboxylic acid 1-alkyl 2-aryl ester of formula (III) is not isolated;
and is
Wherein R and R' and R1Independently of one another, represents a methyl group or an ethyl group or a propyl group or a butyl group;
and wherein Ra、Rb、Rc、RdAnd ReIndependently of one another, H or C1-4An alkyl group.
For clarity, some terms used herein are defined as follows:
as used herein, "C" or "C" meansx-yAn-alkyl "group is an alkyl group comprising x to y carbon atoms, i.e. for example, C1-3-an alkyl group is an alkyl group comprising 1 to 3 carbon atoms. The alkyl group may be linear or branched. For example-CH (CH)3)-CH2-CH3Is considered to be C4-an alkyl group. Thus, "propyl" may be "n-propyl" or "isopropyl". Similarly, "butyl" may be "n-butyl" or "isobutyl" or "sec-butyl" or "tert-butyl".
The term "independently of each other" in this context means that in the context of substituents, moieties or groups, the named substituents, moieties or groups may occur simultaneously in different meanings in the same molecule.
In case the same label is present for a symbol or group in several formulae, the definition of said group or symbol in one particular formula also applies herein for other formulae comprising the same said label.
The expression "manufacturing method" is synonymous with "preparation method" or "preparation process" and can be used interchangeably.
In case the same label is present for a symbol or group in several formulae, the definition of said group or symbol in one particular formula also applies herein for other formulae comprising the same said label.
One key factor of the present invention is that the process is a one-pot reaction. It has surprisingly been found that this reaction comprising step a) and step b) is carried out in the formula CH3The COOR' is carried out very efficiently in the alkyl acetate solvent, which allows the entire process to be carried out as a one-pot reaction, i.e. without the necessity of isolating the intermediate product of formula (III), and correspondingly without the solvent change required for step a) and step b).
The proposed manufacturing method therefore presents significant advantages not only in terms of economy, but also in terms of ecology. The yield of the proposed solution is still significantly high.
Step a)
Figure BDA0002845443720000041
In step a), an alkyl hydrazine carboxylate of formula (II) is reacted with an aryl chloroformate to form the intermediate 1-alkyl 2-aryl hydrazine-1,2-dicarboxylate of formula (III).
Preferably, R isa、Rb、Rc、RdAnd ReRepresents H or methyl or ethyl, more preferably H or methyl. Preferably, the substituent Ra、Rb、Rc、RdAnd ReWherein no more than two substituents represent C1-4-an alkyl group.
Ra、Rb、Rc、RdAnd ReThe preferred combination of (a) and (b) is:
-Ramethyl or ethyl, preferably methyl, Rb＝Rc＝Rd＝Re＝H
-RbMethyl or ethyl, preferably methyl, Ra＝Rc＝Rd＝Re＝H
-RcMethyl or ethyl, preferably methyl, and Ra＝Rb＝Rd＝Re＝H
-Ra＝ReMethyl or ethyl, preferably methyl, Rb＝Rc＝Rd＝H
-Rb＝RdMethyl or ethyl, preferably methyl, Ra＝Rc＝Re＝H
-Ra＝Rb＝Rc＝Rd＝Re＝H。
In a most preferred embodiment, all substituents Ra、Rb、Rc、RdAnd ReBoth represent H, i.e. the preferred aryl chloroformate is phenyl chloroformate.
Phenyl chloroformate is commercially available from various suppliers.
The alkyl hydrazinecarboxylates of formula (II) (also known as alkyl carbazates) contain a substituent R. R represents a methyl group or an ethyl group or a propyl group or a butyl group.
Figure BDA0002845443720000051
In one embodiment, R preferably represents an ethyl group or a propyl group or a butyl group, more preferably a methyl group, an n-propyl group, an isopropyl group, an n-butyl group or an isobutyl group or a sec-butyl group.
In another preferred embodiment, R preferably represents an ethyl group or a propyl group or a butyl group, most preferably an ethyl group.
Alkyl hydrazine carboxylate esters of formula (II) are commercially available from various suppliers.
As mentioned above, the reaction step is carried out in a solvent of the formula CH3COOR' in alkyl acetate. Since R' represents a methyl group or an ethyl group or an isopropyl group or a butyl group, the solvent is selected from the group consisting of methyl acetate, ethyl acetate, n-propyl acetate, isopropyl acetate, n-butyl acetate, isobutyl acetate, sec-butyl acetate and tert-butyl acetate.
Such solvents are very advantageous in ecotoxicological terms and in terms of work safety in comparison with other solvents, such as acetonitrile or dichloromethane.
Preferably, R' represents an ethyl group or a propyl group or a butyl group, more preferably a butyl group or an isopropyl group, even more preferably an n-butyl or isopropyl group. Most preferably, R' represents an n-butyl group. Thus, the preferred solvent is n-butyl acetate.
The molar ratio of alkyl hydrazinecarboxylate to aryl chloroformate of formula (II) is preferably in the range of 1.1:1 and 1:1.1, more preferably 1:1.
Preferably, the alkyl ester of hydrazine carboxylate is first dissolved in the formula CH3COOR' and then aryl chloroformate. Preferably, the aryl chloroformate is added slowly,preferably with stirring.
Preferably, step a) is carried out in the presence of a base. The base is preferably added to the alkyl hydrazine carboxylate prior to the addition of the aryl chloroformate.
Preferably, the base is an alkali metal carbonate or alkaline earth metal carbonate or alkali metal bicarbonate or alkaline earth metal bicarbonate, or a salt of acetic acid (potassium acetate), or an aliphatic tertiary amine or alicyclic amine or an N-containing heteroaromatic compound, such as pyridine or pyrrole or picoline or pyrimidine. Preferred tertiary or alicyclic aliphatic amines are triethylamine, tripropylamine, triisopropylamine, tributylamine or N, N-diisopropylethylamine.
Preferably, the base is sodium carbonate or pyridine, in particular pyridine.
The amount of base is preferably selected so that it is at least the molar amount of aryl chloroformate. More preferably, the amount of base is at least 10% excess relative to the molar amount of aryl chloroformate.
As a result of step a), the intermediate hydrazine-1, 2-dicarboxylic acid 1-alkyl 2-aryl ester of the formula (III) is formed.
The intermediate can in principle be isolated, but since this is not essential in the present invention, the reaction is continued directly to reaction step b).
Step b)
Figure BDA0002845443720000071
In step b), the intermediate hydrazine-1, 2-dicarboxylic acid 1-alkyl 2-aryl ester formed in step a) of formula (III) is reacted with an alkylamine of formula (IV) to give the compound of formula (I).
The primary amine of formula (IV) contains a substituent R1。R1Represents a methyl group or an ethyl group or a propyl group or a butyl group.
R1Preferably represents a methyl group or an ethyl group or a propyl group, preferably a methyl group or an ethyl group or an isopropyl group.
The molar ratio of primary amine of formula (IV) to intermediate hydrazine-1, 2-dicarboxylic acid 1-alkyl 2-aryl ester of formula (III) is preferably in the range between 2.5:1 and 1:1, more preferably between 1.5:1 and 1:1.
The alkylamine of formula (IV) is generally added slowly, preferably with stirring.
Both reaction step a) and reaction step b) are carried out in the same solvent, which is of formula CH as described above3Alkyl acetate of COOR'. The reaction step a) and the reaction step b) are preferably carried out in the same reaction vessel.
Furthermore, steps a) and b) are preferably carried out at a temperature in the range between 0 ℃ and 50 ℃, in particular in the range between 5 ℃ and 40 ℃.
Even more preferably, step a) is carried out at a temperature in the range between 5 ℃ and 30 ℃, most preferably in the range between 5 ℃ and 25 ℃.
Even more preferably, step b) is carried out at a temperature in the range between 5 ℃ and 35 ℃, most preferably in the range between 10 ℃ and 30 ℃.
It is furthermore preferred that step a) and/or step b) are carried out at ambient pressure.
It is further preferred that R is different from R', and/or R is different from R1Different. Most preferably, all substituents R, R' and R1Are different from each other. Preferred embodiments employ R, R' and R below1A combination of R:
-R ═ ethyl, R1Methyl, R' ═ n-butyl;
-R ═ ethyl, R1Methyl, R' ═ isopropyl;
-R ═ ethyl, R1Ethyl, R' ═ n-butyl;
-R ═ ethyl, R1Ethyl, R ═ isopropyl;
-R ═ ethyl, R1(ii) isopropyl, R ═ n-butyl;
-R ═ ethyl, R1R' is isopropyl.
The compound of formula (I) is an alkyl 2- (alkylcarbamoyl) hydrazine-1-carboxylate (also known as semicarbazide).
The compounds of formula (I) can be easily converted to compounds of formula (X) in further reactions.
Figure BDA0002845443720000081
Thus, in another aspect, the invention also relates to a process for the manufacture of a compound of formula (X),
Figure BDA0002845443720000082
comprising a step c)
c) Cyclizing the compound of formula (I) in the presence of YOH base to produce a compound of formula (X);
Figure BDA0002845443720000091
wherein Y represents an alkali metal, Z represents H or Y;
and wherein R and R1Independently of one another, represents a methyl group or an ethyl group or an isopropyl group or a butyl group.
The compound of formula (X) is an alkylurazole salt.
The cyclization reaction is very efficient.
Of course, the compounds of formula (I) are preferably prepared as detailed above.
Preferably, Y is an alkali metal, preferably K or Na.
Preferably, Y is Na.
The reaction of step c) is preferably carried out in the presence of an organic solvent (S), in particular in the presence of ethanol. Preferably, the organic solvent is anhydrous.
More preferably, the reaction of step c) is carried out at elevated temperature, in particular at the reflux temperature of the solvent.
During the reaction, the compound of formula (X) is usually precipitated and can be easily filtered off.
The molar ratio of the YOH base to the compound of formula (I) is preferably at least 1, usually at least 1.2. When this ratio is increased significantly from 1, the amount of disalt (i.e., formula (X), where Z ° -Y) increases significantly.
It has been found that compounds of formula (X) can be directly oxidized to compounds of formula (XII) (═ 4-alkyl-1, 2, 4-triazoline-3, 5-dione).
Figure BDA0002845443720000101
Thus, in another aspect, the invention relates to a process for making a compound of formula (XII) by direct oxidation of a compound of formula (X) with an oxidizing agent (Ox).
The compound of formula (X) may be directly oxidized to the compound of formula (XII). In this context, "directly" means that the compound of formula (X) does not need to be first converted into the corresponding alkylurazole compound of formula (XI) (═ 4-alkyl-1, 2, 4-triazoline-3, 5-dione).
Figure BDA0002845443720000102
Very advantageously, the salt can be oxidized directly by the oxidizing agent (Ox) to the compound of formula (XII).
The compound of formula (XII) can be used as a dienophile in a Diels-Alder reaction.
Figure 1 schematically shows the reactions relevant to the present invention.
In a first aspect, a process for the manufacture of a compound of formula (I) comprising in a solvent CH is shown3Reaction step a) and reaction step b) in COOR' without isolation of the intermediate of formula (III).
In another aspect, a process for making a compound of formula (X) is shown, comprising a cyclization step c) in the presence of a YOH base.
In another aspect, a method of making a compound of formula (XII) by oxidizing a compound of formula (X) is shown.
The compound of the formula (III-A) and the compound of the formula (X-A) are novel compounds.
Thus, in another aspect, the invention also relates to a compound of formula (III-A), which is a particular embodiment of the compound of formula (III),
Figure BDA0002845443720000111
wherein R' represents CH3Or CH2CH2CH3Or CH (CH)3)2Or CH2CH2CH2CH3Or CH2CH(CH3)2Or CH (CH)3)CH2CH3And wherein R isa、Rb、Rc、RdAnd ReIndependently of one another, H or C1-4-an alkyl group.
In a further aspect, the present invention also relates to a compound of formula (X-A), which is a specific embodiment of the compound of formula (X),
Figure BDA0002845443720000112
wherein R is1'Represents a methyl group or an ethyl group or a propyl group, preferably a methyl group or an ethyl group or an isopropyl group,
and Y represents an alkali metal and Z represents H or Y.
The compounds of the formula (III-A) and the compounds of the formula (X-A) are particularly suitable for use in the processes discussed in detail above.
Examples
The invention is further illustrated by the following experiments.
1Example a 1.2- (methylcarbamoyl) hydrazine-1-carboxylic acid ethyl ester (formula (I), R ═ methyl, R ═ ethyl), (R' Isopropyl) synthesis
Step a):
formation of hydrazine-1, 2-dicarboxylic acid 1-ethyl 2-aryl ester (formula (III), R ═ ethyl)
A500 mL round bottom flask was charged with 64.4 g (0.61 mol, 1.0 eq.) of ethyl carbazate and 156 g of isopropyl acetate. After dissolution 76.4 g (0.72 mol, 1.2 eq) Na were added2CO3. The suspension was cooled to 10 ℃ and 96.1 g (0.61 mol, 1.0 eq) phenyl chloroformate was added over 45 minutes, maintaining the reaction temperature between 10 ℃ and 20 ℃. After addition, CO is formed2. Stirring was continued at 25 ℃ for 2 hours until a conversion of 99% was reached. 600 g of water were added and after stirring for 15 minutes, the lower aqueous phase was drained off. The product was identified as hydrazine-1, 2-dicarboxylic acid 1-ethyl-2-phenyl ester.
Step b):
2- (methylcarbamoyl) hydrazine-1-carboxylic acid ethyl ester (formula (I), R)1Methyl, R ═ ethyl) formation
In the organic phase of 91.5 g (0.97 mol, 1.6 eq) of 1-ethyl-2-phenyl hydrazine-1,2-dicarboxylate prepared in step a) above was added 33% w/w methylamine in ethanol, without any isolation of 1-ethyl-2-phenyl hydrazine-1,2-dicarboxylate, and the reaction temperature was kept below 25 ℃. After about 30 minutes, the mixture became a yellowish suspension. Stirring was continued at 25 ℃ for 5 hours until a conversion of 99% was reached. 200 g of excess methylamine, ethanol and isopropyl acetate were distilled off (40 ℃, 75 mbar). The reaction mixture was cooled to 10 ℃ and the product was filtered. After washing the filter cake with cold isopropyl acetate (3 times 26 g each), the product was dried (80 ℃, 1 mbar) yielding 78.0 g of ethyl 2- (methylcarbamoyl) hydrazine-1-carboxylate (99% w/w, 79% yield).
Example a2-a 32- (alkylcarbamoyl) hydrazine-1-carboxylic acid ethyl ester (formula (I), R ═ ethyl) synthesis
In example A2-A3, the corresponding compound of formula (I) has been prepared in a one-pot reaction in the same manner as described in example A1. Substances A2 and A3 have been identified.
Examples R1 R'
A2 Ethyl radical Isopropyl group
A3 Isopropyl group Isopropyl group
1Example A42- (methylcarbamoyl) hydrazine-1-carboxylic acid ethyl ester (formula (I), R ═ methyl, R ═ ethyl) in ethyl Synthesis in n-butyl acid
In example A4, ethyl 2- (methylcarbamoyl) hydrazine-1-carboxylate was prepared in a one-pot reaction as in example A1, using n-butyl acetate as the corresponding solvent in both step a) and step b).
Examples R'
A4 N-butyl
It was found that ethyl 2- (methylcarbamoyl) hydrazine-1-carboxylate prepared in example A4 was the same as prepared in example A1.
Example B1 Synthesis of 5-hydroxy-4-methyl-4H-1, 2, 4-triazole-3-sodium oleate (methyl urazole monosodium salt)
1(formula (X), R ═ methyl, Y ═ Na, Z ═ H)
Step c):
a250 mL round bottom flask was charged with 9.0 g (0.23 mol, 1.2 eq.) of solid NaOH and 103 g of anhydrous methanol. After dissolution, 30.0 g (0.19 mol, 1.0 eq) of ethyl 2- (methylcarbamoyl) hydrazine-1-carboxylate, as prepared in example a1, were added, and 16 g of methanol were added again. The reaction mixture was refluxed for 3.5 hours until a conversion of 99% was reached. The pale yellow suspension was cooled to 5 ℃ and the product was filtered. After washing the filter cake with cold methanol (2 times 24 g each), the product was dried (40 ℃, 1 mbar) to give 21.9 g of methylurazole monosodium salt (98.5% w/w, 83% yield), which had been characterized by NMR:
1H-NMR(300MHz，D2O)：δ(ppm)＝3.01(s，3H)
13C-NMR(75MHz，D2O)：δ(ppm)＝24.9，157.7。
examples B2-B3
5-hydroxy-4-alkyl-4H-1, 2, 4-triazole-3-oleate sodium (alkylurazole monosodium salt) (formula (X), Y ═ Na, Z ═ H) Synthesis of (2)
In examples B2-B3, based on the ethyl-2- (alkylcarbamoyl) hydrazine-1-carboxylate series as prepared in examples A2-A3, the corresponding compound of formula (X) has been prepared in the same manner as described in example B1. These substances have been identified and characterized by NMR.
Examples R1
B2 Ethyl radical
B3 Isopropyl group
Characterization of
B2：
1H-NMR(300MHz,D2O):δ(ppm)＝1.17(t,3H,J＝7.25Hz),3.50(q,2H,J＝7.25Hz)
13C-NMR(75MHz,D2O):δ(ppm)＝13.3,33.8,156.5。
B3:
1H-NMR(300MHz,D2O):δ(ppm)＝1.40(d,6H,J＝6.99Hz),4.16(h,1H,J＝6.99Hz)
13C-NMR(75MHz,D2O):δ(ppm)＝19.3,43.5,156.5。
Examples C2-C3
Direct oxidation synthesis of 4-alkyl-3H-1, 2, 4-triazole-3, 5(4H) -diketone (═ 4-alkyl-1, 2, 4-triazoline- 3, 5-diketones)
Sodium 5-hydroxy-4-methyl-4H-1, 2, 4-triazole-3-oleate (275 mg, 1.70 mmol) (B1) was suspended in ethyl acetate (3.9 ml). A solution of HCl in ethyl acetate (3.8 ml, 3.8 mmol, 1M) was added slowly. 1,3, 5-trichloro-1, 3, 5-triazinane-2, 4, 6-trione (125 mg, 0.54 mmol) in ethyl acetate (1.7 ml) was added dropwise over 10 minutes. The white suspension immediately turned pink and was stirred for 30 minutes. The suspension was filtered and the filter cake was washed with ethyl acetate (2.5 ml).
In a flask, sodium 5-hydroxy-4-ethyl-4H-1, 2, 4-triazole-3-oleate (1.25 g, 6.76 mmol) (B2) was suspended in ethyl acetate (26.1 ml) under argon and a solution of HCl in ethyl acetate (7 ml, 7 mmol, 1M) was added slowly. A solution of 1,3, 5-trichloro-1, 3, 5-triazinane-2, 4, 6-trione (0.61 g, 2.37 mmol) in ethyl acetate (1.7 ml) was added dropwise over 10 minutes. The white suspension immediately turned pink and was stirred for 30 minutes.
In a flask, sodium 5-hydroxy-4-isopropyl-4H-1, 2, 4-triazole-3-oleate (1.58 g, 6.63 mmol) (B3) was suspended in ethyl acetate (26.1 ml) under argon and a solution of HCl in ethyl acetate (7 ml, 7 mmol, 1M) was added slowly. A solution of 1,3, 5-trichloro-1, 3, 5-triazinane-2, 4, 6-trione (0.60 g, 2.32 mmol) in ethyl acetate (1.7 ml) was added dropwise over 10 minutes. The white suspension immediately turned pink and was stirred for 30 minutes.
The oxidation was performed quantitatively and the products were identified by NMR and MS (C1, C2, and C3).
Figure BDA0002845443720000151
Table 1 direct oxidation of a compound of formula (X) to the corresponding compound of formula (XII).

Claims (14)

1. A process for the manufacture of a compound of formula (I) in a one-pot reaction,
Figure FDA0002845443710000011
the method comprises the step a)
a) Reacting an alkyl hydrazine carboxylate of formula (II) with an aryl chloroformate to form an intermediate 1-alkyl 2-aryl hydrazine-1,2-dicarboxylate of formula (III),
Figure FDA0002845443710000012
followed by step b)
b) Reacting the intermediate hydrazine-1, 2-dicarboxylic acid 1-alkyl 2-aryl ester of formula (III) with an alkylamine of formula (IV) to produce a compound of formula (I)
R1-NH2 (IV)
It is characterized in that the preparation method is characterized in that,
the reaction of steps a) and b) is of formula CH3COOR' in an alkyl acetate solvent; and is
The intermediate hydrazine-1, 2-dicarboxylic acid 1-alkyl 2-aryl ester of formula (III) is not isolated;
and is
Wherein R and R' and R1Independently of one another, represents a methyl group or an ethyl group or a propyl group or a butyl group,
and wherein Ra、Rb、Rc、RdAnd ReIndependently of one another, H or C1-4An alkyl group.
2. The method according to claim 1, characterized in that R is an ethyl group or a propyl group or a butyl group, most preferably an ethyl group.
3. The method according to claim 1 or claim 2, characterized in that R1Is a methyl group or an ethyl group or a propyl group, preferably a methyl group or an ethyl group or an isopropyl group.
4. Process according to any one of the preceding claims, characterized in that R' is an ethyl group or a propyl group or a butyl group, preferably a butyl group or an isopropyl group.
5. Process according to any one of the preceding claims, characterized in that R is different from R', and/or R is different from R1Different.
6. The process according to any of the preceding claims, characterized in that a base is used in step a).
7. The method according to any of the preceding claims, characterized in that step a) and/or step b) is carried out at a temperature in the range between 0 ℃ and 50 ℃, in particular in the range between 5 ℃ and 40 ℃.
8. A process for the manufacture of a compound of formula (X),
Figure FDA0002845443710000021
the method comprises a step c)
c) Cyclizing the compound of formula (I) in the presence of YOH base to produce a compound of formula (X);
Figure FDA0002845443710000031
wherein Y represents an alkali metal, Z represents H or Y;
and wherein R and R1Independently of one another, represents a methyl group or an ethyl group or an isopropyl group or a butyl group.
9. Process according to claim 8, characterized in that the compound of formula (I) in step c) is prepared by a process according to any one of claims 1 to 7.
10. A method according to claim 8 or 9, characterized in that Y ═ Na.
11. Process according to any one of the preceding claims 8 to 10, characterized in that step c) is carried out in the presence of an organic solvent (S), in particular ethanol.
12. A process for producing a compound of the formula (XII) by directly oxidizing a compound of the formula (X) with an oxidizing agent (Ox),
Figure FDA0002845443710000032
wherein Y represents an alkali metal, Z represents H or Y;
and wherein R1Represents a methyl group or an ethyl group or an isopropyl group or a butyl group.
13. A compound of the formula (III-A),
Figure FDA0002845443710000041
wherein R' represents CH3Or CH2CH2CH3Or CH (CH)3)2Or CH2CH2CH2CH3Or CH2CH(CH3)2Or CH (CH)3)CH2CH3；
And wherein Ra、Rb、Rc、RdAnd ReIndependently of one another, H or C1-4An alkyl group.
14. A compound of the formula (X-A),
Figure FDA0002845443710000042
wherein R is1' represents a methyl group or an ethyl group or a propyl group, preferably a methyl group or an ethyl group or an isopropyl group,
and Y represents an alkali metal and Z represents H or Y.
CN202011507935.0A 2019-12-19 2020-12-18 Preparation of alkyl 2- (alkylcarbamoyl) hydrazine-1-carboxylates or their corresponding urazole salts Pending CN113004174A (en)

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3888801A (en) * 1973-04-26 1975-06-10 Uniroyal Inc Gas-expanding polymers using hydrazodicarboxylates
CN1351990A (en) * 2001-11-09 2002-06-05 上海试四赫维化工有限公司 Process for preparing 4-phenyl urazole

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3888801A (en) * 1973-04-26 1975-06-10 Uniroyal Inc Gas-expanding polymers using hydrazodicarboxylates
CN1351990A (en) * 2001-11-09 2002-06-05 上海试四赫维化工有限公司 Process for preparing 4-phenyl urazole

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
GARY W. BRETON ET AL.: "Alternative synthetic routes to N-methyl-1, 2, 4-triazoline-3, 5-dione (MeTAD) and other triazolinedione derivatives", 《TETRAHEDRON LETTERS》, vol. 55, pages 4661 - 4663, XP029040816, DOI: 10.1016/j.tetlet.2014.06.091 *
MOHAMMAD ALI ZOLFIGOL ET AL.: "Trichloroisocyanuric Acid as a Novel Oxidizing Agent for the Oxidation of Urazoles Under Both Heterogeneous and Solvent Free Conditions", 《SYNLETT》, pages 1633 - 1636 *

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