CN103880846B - A kind of preparation method of triazolo pyrimidine mercapto radical-type compound - Google Patents

A kind of preparation method of triazolo pyrimidine mercapto radical-type compound Download PDF

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CN103880846B
CN103880846B CN201410089040.8A CN201410089040A CN103880846B CN 103880846 B CN103880846 B CN 103880846B CN 201410089040 A CN201410089040 A CN 201410089040A CN 103880846 B CN103880846 B CN 103880846B
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formula
preparation
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CN103880846A (en
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胡俊铎
赖玉龙
刘维
郭群震
虞小华
蔡国平
陈邦池
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Oriental Luzhou Agrochemicals Co Ltd
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Oriental Luzhou Agrochemicals Co Ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention discloses the preparation method of a kind of triazolo pyrimidine mercapto radical-type compound, compound shown in formula II is reset replacement under alcohol alkali effect by the method, obtains the radical-type compound of triazolo pyrimidine mercapto shown in formula I.The method has expanded approach and the raw material sources of original preparation method, does not produce by-product disagreeableness to environment, has very much industrial application value.

Description

A kind of preparation method of triazolo pyrimidine mercapto radical-type compound
Technical field
The present invention relates to the synthesis of organic heterocyclic molecule, the especially preparation of triazolo pyrimidine sulfhydryl compound Method.
Technical background
Triazolo pyrimidine sulfhydryl compound (I) is the important centre preparing triazolopyrimidine sulfonamides herbicide Body.
US6162915 and US5488109 discloses a kind of method preparing triazolo pyrimidine sulfhydryl compound. Such as, compound (V) is prepared in formula IV compound and Sodium ethylate reaction.
Although the method conversion ratio is higher, but reaction is supervened the methanthiol of a large amount of foul smelling taste (VI), there is serious environmental issue.
Summary of the invention
The present invention, through in-depth study, finds compound shown in formula II and alcohol alkali reaction, can be prepared into To the compound shown in formula I.Can not only reset due to the method in the triazole ring in formula II Sulfydryl, it is also possible to the methoxyl group on substituted pyrimidines ring, such that it is able to larger range of widening prepares triazolopyrimidine The approach of pyridine mercapto radical-type compound and raw material sources, prepare triazolopyrimidine sulfonamide type for further reduction and remove The cost of material of the grass former medicine of agent provides new method, and by-product is environmentally friendly, and having important industry should By value.
The technical route realizing the present invention is as follows: the preparation method of a kind of triazolo pyrimidine mercapto radical-type compound, Have steps of: by formula II compound
Wherein, R1, R2For the most independent hydrogen, halogen, nitro, C1-C5Alkyl, C1-C5Alcoxyl Base；
Alcohol alkali (III) 1.0 times of-10.0 times of moles
R3OM (III)
Wherein R3For C2-C12Alkyl, M is alkali metal；
Under effect, the alcohol alkali of preferably 1.5-3 times of mole, organic solvent at a certain temperature is reset and takes In generation, post-treated obtain compound described in formula I.
Reaction temperature described in this method is typically carried out at a temperature of-50 DEG C-50 DEG C, and the temperature of 0-30 DEG C is More excellent reaction temperature.
Organic solvent used in this method include methanol, ethanol, acetonitrile, dichloromethane, dichloroethanes, Toluene, dimethylbenzene, oxolane, dioxane, DMSO, DMF, DMAC, NMP, or it is mixed Compound.
The present invention uses a kind of new response strategy, is that raw material resets replacement with alcohol alkali with formula (II) compound Compound (I) is prepared in reaction, and this new reaction by-product is methanol, efficiently solves methanthiol stench and asks Topic, is more beneficial for industrialized production.
Detailed description of the invention
The following examples further illustrate some features of the present invention, but the present invention protected interior Hold and scope is not limited by following embodiment.
Embodiment 1
The preparation of fluoro-[the 1,2,4]-triazol of 5-ethyoxyl-7--[1,5-C]-pyrimidine-2 (3H) thioketone
By 10.0g (0.048mol, purity 96%) fluoro-[1,2, the 4]-triazol of 5-methoxyl group-7--[4,3-C]-pyrimidine -3 (2H) thioketone joins in 40g ethanol.Under the conditions of 0 DEG C-10 DEG C, 5.4g Sodium ethylate is added extremely In above-mentioned solution.Mixture stirs 2h at 0 DEG C-10 DEG C.Then by the dense salt of mixture 9.5g 36% Acid acidifying, adds and filters after-5 DEG C of 30min stirred below after 50g water, and with 20ml cold water and 20ml Cold washing with alcohol filter cake, is dried to obtain 9.2g target compound, and product is beige solid.
NMR(CDCl3)δ:1H:1.47(t,3H),4.69(q,2H),7.04(d,1H).
Embodiment 2
The preparation of chloro-[the 1,2,4]-triazol of 5-ethyoxyl-7--[1,5-C]-pyrimidine-2 (3H) thioketone
By 10.8g (0.048mol, purity 96%) chloro-[1,2, the 4]-triazol of 5-methoxyl group-7--[4,3-C]-pyrimidine -3 (2H) thioketone joins in 40g ethanol.Under the conditions of 0 DEG C-10 DEG C, 5.4g Sodium ethylate is added extremely In above-mentioned solution.Mixture stirs 2h at 0 DEG C-10 DEG C.Then by the dense salt of mixture 9.5g 36% Acid acidifying, adds and filters after-5 DEG C of 30min stirred below after 50g water, and with 20ml cold water and 20ml Cold washing with alcohol filter cake, is dried to obtain 9.5g target compound, and product is beige solid.
Embodiment 3
The preparation of fluoro-[the 1,2,4]-triazol of 5-ethyoxyl-8--[1,5-C]-pyrimidine-2 (3H) thioketone
By 10.0g (0.048mol, purity 96%) fluoro-[1,2, the 4]-triazol of 5-methoxyl group-8--[4,3-C]-pyrimidine -3 (2H) thioketone joins in 40g ethanol.Under the conditions of 0 DEG C-10 DEG C, 5.4g Sodium ethylate is added extremely In above-mentioned solution.Mixture stirs 2h at 0 DEG C-10 DEG C.Then by the dense salt of mixture 9.5g 36% Acid acidifying, adds and filters after-5 DEG C of 30min stirred below after 50g water, and with 20ml cold water and 20ml Cold washing with alcohol filter cake, is dried to obtain 9.2g target compound, and product is beige solid.
Embodiment 4-9
Reaction preparation fluoro-[the 1,2,4]-triazol of 5-ethyoxyl-7--[1,5-C]-pyrimidine-2 (3H) thioketone under different condition Preparation
Embodiment 4-embodiment 9 is with reference to embodiment 1, and raw material puts into and is 10.0g, and reaction condition and product are received Rate see table:
Alcohol alkali Solvent Raw material and the mol ratio of alkali Reaction temperature Product weight
Embodiment 4 Sodium ethylate Ethanol 1:5 0℃ 9.0g
Embodiment 5 Dodecane lithium alkoxide Ethanol 1:10 -50℃ 8.0g
Embodiment 6 Potassium ethoxide Acetonitrile 1:10 -50℃ 7.9g
Embodiment 7 Potassium ethoxide Dichloromethane 1:1.1 -10℃ 8.1g
Embodiment 8 Lithium ethoxide DMSO 1:1.8 50℃ 7.5g
Embodiment 9 Sodium ethylate Toluene 1:1.8 50℃ 9.0g

Claims (7)

1. the preparation method of a triazolo pyrimidine mercapto radical-type compound, it is characterized in that: by compound (II) under alcohol alkali (III) acts on, in organic solvent, carry out resetting substitution reaction under uniform temperature and obtain compound (I)
Wherein the structural formula of compound (I) is:
In formula, R1, R2For the most independent hydrogen, halogen, R3For C2-C12Alkyl；
The structural formula of compound (II) is:
In formula, R1, R2For the most independent hydrogen, halogen；
The structural formula of alcohol alkali (III) is:
R3OM(III)
R in formula3For C2-C12Alkyl, M is alkali metal；
Described organic solvent is one or more in acetonitrile, dichloromethane, dichloroethanes, toluene, dimethylbenzene, oxolane, dioxane, DMSO, DMF, DMAC, NMP.
Method the most according to claim 1, it is characterised in that described R1, R2For hydrogen or halogen, R3For C2-C5Alkyl.
Method the most according to claim 1 and 2, it is characterised in that described R1For H, R2For fluorine, R3For ethyl.
Method the most according to claim 1, it is characterised in that R in described alcohol alkali3For C2-C5Alkyl, alkali metal is one or more in Li, Na, K.
Method the most according to claim 1, it is characterised in that described compound (II) is 1:1 to 1:10 with the mol ratio of alcohol alkali (III).
Method the most according to claim 1, it is characterised in that described rearrangement substitution reaction temperature is-50-50 DEG C.
7. according to the method described in claim 1 or 6, it is characterised in that described rearrangement substitution reaction temperature is preferably 0 DEG C-30 DEG C.
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PCT/CN2015/073741 WO2015135439A1 (en) 2014-03-12 2015-03-06 Triazolo pyrimidine sulfydryl compound preparation method

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CN103880846B (en) * 2014-03-12 2016-09-14 泸州东方农化有限公司 A kind of preparation method of triazolo pyrimidine mercapto radical-type compound

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WO1995012597A1 (en) * 1993-11-05 1995-05-11 Dowelanco 2-alkoxy-4-hydrazinopyrimidine compounds and their use in the preparation of 5-alkoxy-1,2-4-triazolo[4,3-c]pyrimidine-3(2h)-thione compounds
WO1995012595A1 (en) * 1993-11-05 1995-05-11 Dowelanco 5-alkoxy-1,2,4-triazolo[4,3-c]pyrimidine-3(2h)-thione compounds and their use in the preparation of 5-alkoxy[1,2,4]triazolo[1,5-c]pyrimidine-2(3h)-thione and 3-hydrocarbylthio-5-alkoxy-1,2,4-triazolo[4,3-c]pyrimidine compounds
CN1115983A (en) * 1993-11-05 1996-01-31 道伊兰科公司 5-alkoxyl[1,2,4]triazolo[1,5-C]pyrimidine-2(3H)-thione compounds and their use in the preparation of 2,2'-dithiobis(5-alkoxy[1,2,4]triazolo[1,5-C]-pyrimidine) and 2-chlorosulfonyl-5-alkoxy[1,2,4].....
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WO1995012595A1 (en) * 1993-11-05 1995-05-11 Dowelanco 5-alkoxy-1,2,4-triazolo[4,3-c]pyrimidine-3(2h)-thione compounds and their use in the preparation of 5-alkoxy[1,2,4]triazolo[1,5-c]pyrimidine-2(3h)-thione and 3-hydrocarbylthio-5-alkoxy-1,2,4-triazolo[4,3-c]pyrimidine compounds
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