CN105523874A - Preparation method of 2,2-dihalo-1,3-dicarbonyl derivatives - Google Patents
Preparation method of 2,2-dihalo-1,3-dicarbonyl derivatives Download PDFInfo
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Abstract
The invention discloses a method for preparing 2,2-dihalo-1,3-dicarbonyl derivatives. The method is widely applicable to 1,3-dicarbonyl derivatives. The raw materials are easily available, and types are multiple. Types of products obtained by the method are multiple, and the products can be directly used or used in other further reactions. The method has advantages of mild reaction condition, simple reaction operation and post-processing, short reaction time, high yield and little pollution, and is suitable for industrial production.
Description
Technical field
The invention belongs to the preparing technical field of organic compound, be specifically related to a kind of preparation method of 2,2-dihalo-1,3-Dicarbonyl derivatives.
Background technology
Chloro-1, the 3-Dicarbonyl derivatives of 2,2-bis-is the important medicine of a class and pesticide intermediate.Sun discloses a kind of method being prepared the chloro-Resorcinol of 2-by the chloro-hydroresorcinol of 2,2-bis-.The chloro-Resorcinol of 2-is a kind of important medicine and dyestuff intermediate, is widely used in the synthesis of medicine, agricultural chemicals and dyestuff.Its technological line is as follows:
Can prepare 1,3-ring heptadione by 2,2-dichloro suberane-1,3-diketone, it is that an important medicine intermediate is (see Acton, N.; Brossi, A.; Newton, D.L.; Sporn, M.B.J.Med.Chem., 1980,23,805-809).Its technological line is as follows:
Tippe discloses a kind of by 2, the chloro-4-(2 of 2-bis-, 4-dichlorophenoxy)-1-phenyl-1,3-dimethyl diketone (1) prepares 2,2-bis-(4-bromobenzene amido)-4-(2,4-dichlorophenoxy) method of-1-phenyl-1,3-dimethyl diketone (2), compound 1 and 2 Rhizoctonia solani, fusarium culmorum, Phytophthora cactorum all have certain restraining effect; Its technological line is as follows:
By chloro-1, the 3-Dicarbonyl derivatives of 2,2-bis-set out can synthesize can be used for medicine compound 3,5-phenyl-3-amino 1,2,4-triazole (compound 4), treat Parkinsonian drug molecule compound 5; Bromo-1, the 3-Dicarbonyl derivatives of 2,2-bis-or the important brominated reagent of a class.
The synthetic method of published 2,2-bis-chloro-1,3-Dicarbonyl derivatives mainly contains following several:
Utilize KClO
3/ NaHSO
3/ ZnSO
4system prepares chloro-1, the 3-dicarbonyl compound of 2,2-bis-, and the method exists the shortcomings such as substrate narrow application range, operating process is dangerous greatly, material loss is large.With PhICl
2for chlorination reagent prepares the method for chloro-1, the 3-Dicarbonyl derivatives of 2,2-bis-, there is substrate and be difficult to deficiencies such as obtaining, operating process is dangerous greatly, chlorination reagent is expensive in the method.
The synthetic method of published 2,2-bis-bromo-1,3-Dicarbonyl derivatives mainly contains following several:
Polishing prepares bromo-1, the 3-Dicarbonyl derivatives of 2,2-bis-, the method discloses the result of 32,2-bis-bromo-1,3-Dicarbonyl derivatives, there is the deficiencies such as substrate narrow application range, not easily amplification; Utilize Oxone/NH
4br prepares the method for bromo-1, the 3-Dicarbonyl derivatives of 2,2-bis-, and the method is only suitable for 52,2-bis-bromo-1,3-Dicarbonyl derivatives, exist substrate narrow application range, operating process danger greatly, the not easily deficiency such as amplification.
The dihalo technology of published 1,3-Dicarbonyl derivatives exists that substrate is difficult to obtain, substrate narrow application range, severe reaction conditions, halogenating agent are expensive, production cost is high, pollution is large, operation is inconvenient, reaction scale is difficult to the deficiencies such as amplification.Therefore, find and a kind ofly meet that Green Chemistry requires, reaction conditions is gentle, universality method that is good, that be suitable for large-scale production is very important.
Summary of the invention
The object of this invention is to provide the method that one prepares 2,2-dihalo-1,3-Dicarbonyl derivatives, it has simple, the high yield of raw material sources, reaction conditions is gentle, universality is good advantage.
To achieve the above object of the invention, the technical solution used in the present invention is: a kind of 1, the dihalo method of 3-Dicarbonyl derivatives, comprise the following steps: by 1,3-Dicarbonyl derivatives, sodium halide, manganese acetate and copper catalyst add in solvent, react at 30 ~ 90 DEG C, obtain 2,2-dihalo-1,3-Dicarbonyl derivatives;
Described 1,3-Dicarbonyl derivatives is as shown in following chemical structure of general formula:
Wherein R
1be selected from: the one in alkyl, aryl, heteroaryl or alkoxyl group; R
2be selected from: the one in alkyl, aryl, heteroaryl or alkoxyl group;
Described sodium halide is Sodium Bromide or sodium-chlor;
The chemical formula of described copper catalyst is CuX
n, wherein X is Cl or Br;
Described solvent is selected from: the one in methyl alcohol, ethanol, ethylene glycol, acetonitrile, acetic acid, propionic acid, dimethyl formamide.
Described 2,2-dihalo-1,3-Dicarbonyl derivatives are as shown in following chemical structure of general formula:
or
.
In technique scheme, described 1,3-Dicarbonyl derivatives is selected from ethyl benzoylacetate, (4-toluyl) ethyl acetate, (4-methoxybenzoyl) ethyl acetate, (2-toluyl) ethyl acetate, (2-methoxybenzoyl) ethyl acetate, naphthoyl ethyl acetate, (4-chlorobenzoyl) ethyl acetate, (4-Bromophenacyl) ethyl acetate, (4-oil of mirbane formyl) ethyl acetate, (3-Bromophenacyl) ethyl acetate, 1,3-diphenylpropane-1，3-dione, 1-(2-furyl)-3-phenyl-1,3-propanedione, 1-(2-thienyl)-3-phenyl-1,3-propanedione, 1-(2-pyrryl)-3-phenyl-1,3-propanedione, 1-(4-aminomethyl phenyl)-3-phenyl-1,3-propanedione, 1-(4-p-methoxy-phenyl)-3-phenyl-1,3-propanedione, 1-(2-aminomethyl phenyl)-3-phenyl-1,3-propanedione, 1,3-bis-(2-p-methoxy-phenyl)-1,3-propanedione, 1-phenyl-1,3-diacetylmethane, 1-(4-chloro-phenyl-)-3-phenyl-1,3-propanedione, 1-(4-bromophenyl)-3-phenyl-1,3-propanedione, 3-oxopentanoic acid methyl ester, 1,3-diacetylmethane, 3,5-heptadione, one in diethyl malonate.
In technique scheme, thin-layer chromatography (TLC) is utilized to follow the tracks of reaction until terminate completely.
The present invention for raw material with Sodium Bromide or sodium-chlor, reacts with 1,3-Dicarbonyl derivatives and prepares product; When getting sodium-chlor, in molar ratio, 1,3-Dicarbonyl derivatives: sodium halide: manganese acetate: copper catalyst is for being 1: 2: (2 ~ 8): (0.08 ~ 0.12); Preferably, 1,3-Dicarbonyl derivatives: manganese acetate: copper catalyst is for being 1: 4: 0.1.When getting Sodium Bromide, in molar ratio, 1,3-Dicarbonyl derivatives: sodium halide: manganese acetate: copper catalyst is for being 1: 2: (6 ~ 8): (0.08 ~ 0.12); Preferably, 1,3-Dicarbonyl derivatives: manganese acetate: copper catalyst is for being 1: 7: 0.1.
In preferred technical scheme, reaction terminates to carry out column chromatography for separation purification processes to product afterwards; Be eluent with petrol ether/ethyl acetate during column chromatography for separation purification processes, the volume ratio of preferred sherwood oil and ethyl acetate is 20: 1.
Preferred temperature of reaction of the present invention is 60 ~ 70 DEG C.Reaction temperature and, product yield is high, avoids energy dissipation.
The reaction process of technique scheme can be expressed as:
Due to the utilization of technique scheme, the present invention compared with prior art has following advantages:
1. the present invention uses 1,3-Dicarbonyl derivatives, sodium halide to be initiator first, only under manganese acetate and copper catalyst exist, in air, efficiently prepares 2,2-dihalo-1,3-Dicarbonyl derivatives; Raw material is easy to get, kind is many, and the product prepared can directly use, and can also be used for other further react as intermediate.
2. the present invention uses raw material simple, and without the need to the multiple reagents that prior art requires, reagent dosage is few, and selectivity is good, and cost is low, and avoids the application of existing toxic compounds, decreasing pollution environment; Only need a small amount of catalyzer efficiently can obtain product, not only simplify the purification process of product, reduce the generation of waste, and manganese acetate and copper catalyst reusable edible, avoid wastage of material, for industrial application, there is positive realistic meaning.
3. preparation method's reaction conditions disclosed by the invention is simple, without the need to the complicated atmosphere of prior art, in air, reaction efficiently can obtain product, aftertreatment is very simple, column chromatography, avoid the Hazard Factor that existing reaction process exists, be conducive to chemosynthesis safety in production, ensure the security of the lives and property.
4. in method disclosed by the invention, reaction is carried out in atmosphere, and reaction conditions is gentle, pollute little, the reaction times is short, is specially adapted to multiple 1,3-Dicarbonyl derivatives, the yield of target product is high, and operation and last handling process simply, are suitable for suitability for industrialized production.
Embodiment
Below in conjunction with embodiment, the invention will be further described:
The synthesis of embodiment one: 2,2-dibromo ethyl benzoylacetate
Using ethyl benzoylacetate, Sodium Bromide as raw material, its reactions steps is as follows:
ethyl benzoylacetate (0.192g, 1mmol), Sodium Bromide (0.206g, 2mmol), cuprous bromide (0.014g, 0.1mmol), manganese acetate (1.89g, 7mmol) and methyl alcohol (10 milliliters) is added, 30 DEG C of reactions in reaction flask;
tLC follows the tracks of reaction until terminate completely;
the crude by column chromatography obtained after reaction terminates is separated (ethyl acetate: sherwood oil=1:20), obtains target product (productive rate 79%).The analytical data of product is as follows:
1hNMR (400MHz, CDCl
3): δ 8.22 – 7.80 (m, 2H), 7.65 – 7.54 (m, 1H), 7.50 – 7.37 (m, 2H), 4.28 (q, J=7.1Hz, 2H), 1.13 (t, J=7.1Hz, 3H).
The synthesis of embodiment two: 2,2-dichloro-benzoyl ethyl acetate
Using ethyl benzoylacetate, sodium-chlor as raw material, its reactions steps is as follows:
ethyl benzoylacetate (0.192g, 1mmol), sodium-chlor (0.116g, 2mmol), cuprous chloride (0.010g, 0.1mmol), manganese acetate (1.89g, 7mmol) and ethanol (10 milliliters) is added, 40 DEG C of reactions in reaction flask;
tLC follows the tracks of reaction until terminate completely;
the crude by column chromatography obtained after reaction terminates is separated (ethyl acetate: sherwood oil=1:20), obtains target product (productive rate 81%).The analytical data of product is as follows:
1hNMR (400MHz, CDCl
3): δ 8.42 – 7.80 (m, 2H), 7.67 – 7.54 (m, 1H), 7.50 – 7.37 (m, 2H), 4.28 (q, J=7.1Hz, 2H), 1.13 (t, J=7.1Hz, 3H).
The synthesis of embodiment three: 2,2-dibromo (4-toluyl) ethyl acetate
Using (4-toluyl) ethyl acetate, Sodium Bromide as raw material, its reactions steps is as follows:
(4-toluyl) ethyl acetate (0.206g, 1mmol), Sodium Bromide (0.206g, 2mmol), cuprous iodide (0.020g, 0.1mmol), manganese acetate (1.89g, 7mmol) and acetonitrile (10 milliliters) is added, 50 DEG C of reactions in reaction flask;
tLC follows the tracks of reaction until terminate completely;
the crude by column chromatography obtained after reaction terminates is separated (ethyl acetate: sherwood oil=1:20), obtains target product (productive rate 77%).The analytical data of product is as follows:
1hNMR (400MHz, CDCl
3): δ 7.91 (d, J=8.4Hz, 2H), 7.24 (d, J=8.2Hz, 2H), 4.29 (q, J=7.1Hz, 2H), 2.42 (s, 3H), 1.16 (t, J=7.1Hz, 3H).
The synthesis of embodiment four: 2,2-dibromo (4-methoxybenzoyl) ethyl acetate
Using (4-methoxybenzoyl) ethyl acetate, Sodium Bromide as raw material, its reactions steps is as follows:
(4-methoxybenzoyl) ethyl acetate (0.222g, 1mmol), Sodium Bromide (0.206g, 2mmol), cupric chloride (0.013g, 0.1mmol), manganese acetate (1.89g, 7mmol) and acetic acid (10 milliliters) is added, 60 DEG C of reactions in reaction flask;
tLC follows the tracks of reaction until terminate completely;
the crude by column chromatography obtained after reaction terminates is separated (ethyl acetate: sherwood oil=1:20), obtains target product (productive rate 81%).The analytical data of product is as follows:
1hNMR (400MHz, CDCl
3): δ 8.12 – 7.90 (m, 2H), 6.91 (d, J=9.0Hz, 2H), 4.29 (q, J=7.1Hz, 2H), 3.87 (s, 3H), 1.17 (t, J=7.1Hz, 3H).
The synthesis of embodiment five: 2,2-dibromo (2-toluyl) ethyl acetate
Using (2-toluyl) ethyl acetate, Sodium Bromide as raw material, its reactions steps is as follows:
(2-toluyl) ethyl acetate (0.206g, 1mmol), Sodium Bromide (0.206g, 2mmol), cupric chloride (0.013g, 0.1mmol), manganese acetate (1.89g, 7mmol) and propionic acid (10 milliliters) is added, 70 DEG C of reactions in reaction flask;
tLC follows the tracks of reaction until terminate completely;
the crude by column chromatography obtained after reaction terminates is separated (ethyl acetate: sherwood oil=1:20), obtains target product (productive rate 76%).The analytical data of product is as follows:
1hNMR (400MHz, CDCl
3): δ 7.79 (d, J=7.9Hz, 1H), 7.40 (t, J=7.6Hz, 1H), 7.29 (d, J=7.6Hz, 1H), 7.20 (t, J=7.7Hz, 1H), 4.26 (q, J=7.1Hz, 2H), 2.46 (s, 3H), 1.15 (t, J=7.1Hz, 3H).
The synthesis of embodiment six: 2,2-dibromo (2-methoxybenzoyl) ethyl acetate
Using (2-methoxybenzoyl) ethyl acetate, Sodium Bromide as raw material, its reactions steps is as follows:
(2-methoxybenzoyl) ethyl acetate (0.222g is added in reaction flask, 1mmol), Sodium Bromide (0.206g, 2mmol), cuprous iodide (0.020g, 0.1mmol), manganese acetate (1.89g, 7mmol) with dimethyl formamide (10 milliliters), 80 DEG C of reactions;
tLC follows the tracks of reaction until terminate completely;
the crude by column chromatography obtained after reaction terminates is separated (ethyl acetate: sherwood oil=1:20), obtains target product (productive rate 82%).The analytical data of product is as follows:
1hNMR (400MHz, CDCl
3): δ 7.95 (dd, J=7.9,1.7Hz, 1H), 7.64 – 7.48 (m, 1H), 7.15 – 7.03 (m, 1H), 6.95 (d, J=8.4Hz, 1H), 4.26 (q, J=7.1Hz, 2H), 3.81 (s, 3H), 1.21 (t, J=7.1Hz, 3H).
The synthesis of embodiment seven: 2,2-dibromine naphthalene malonaldehydic acid ethyl ester
Using naphthoyl ethyl acetate, Sodium Bromide as raw material, its reactions steps is as follows:
naphthoyl ethyl acetate (0.242g, 1mmol), Sodium Bromide (0.206g, 2mmol), cuprous iodide (0.020g, 0.1mmol), manganese acetate (1.89g, 7mmol) and dimethyl formamide (10 milliliters) is added, 90 DEG C of reactions in reaction flask;
tLC follows the tracks of reaction until terminate completely;
the crude by column chromatography obtained after reaction terminates is separated (ethyl acetate: sherwood oil=1:20), obtains target product (productive rate 84%).The analytical data of product is as follows:
1hNMR (400MHz, CDCl
3): δ 8.20 (d, J=8.5Hz, 1H), 8.09 (d, J=7.3Hz, 1H), 8.01 (d, J=8.2Hz, 1H), 7.89 (d, J=7.7Hz, 1H), 7.65 – 7.59 (m, 1H), 7.59 – 7.53 (m, 1H), 7.46 (t, J=7.8Hz, 1H), 4.21 (q, J=7.1Hz, 2H), 1.01 (t, J=7.1Hz, 3H).
The synthesis of embodiment eight: 2,2-dibromo (4-chlorobenzoyl) ethyl acetate
Using (4-chlorobenzoyl) ethyl acetate, Sodium Bromide as raw material, its reactions steps is as follows:
(4-chlorobenzoyl) ethyl acetate (0.226g, 1mmol), Sodium Bromide (0.206g, 2mmol), cupric bromide (0.022g, 0.1mmol), manganese acetate (1.89g, 7mmol) and acetic acid (10 milliliters) is added, 30 DEG C of reactions in reaction flask;
tLC follows the tracks of reaction until terminate completely;
the crude by column chromatography obtained after reaction terminates is separated (ethyl acetate: sherwood oil=1:20), obtains target product (productive rate 77%).The analytical data of product is as follows:
1hNMR (400MHz, CDCl
3): δ 7.95 (d, J=8.6Hz, 2H), 7.41 (d, J=8.6Hz, 2H), 4.28 (q, J=7.1Hz, 2H), 1.16 (t, J=7.1Hz, 3H).
The synthesis of embodiment nine: 2,2-dibromo (4-Bromophenacyl) ethyl acetate
Using (4-Bromophenacyl) ethyl acetate, Sodium Bromide as raw material, its reactions steps is as follows:
(4-Bromophenacyl) ethyl acetate (0.269g, 1mmol), Sodium Bromide (0.206g, 2mmol), cupric bromide (0.022g, 0.1mmol), manganese acetate (1.89g, 7mmol) and acetic acid (10 milliliters) is added, 40 DEG C of reactions in reaction flask;
tLC follows the tracks of reaction until terminate completely;
the crude by column chromatography obtained after reaction terminates is separated (ethyl acetate: sherwood oil=1:20), obtains target product (productive rate 73%).The analytical data of product is as follows:
1hNMR (400MHz, CDCl
3): δ 7.88 (d, J=8.7Hz, 2H), 7.60 (d, J=8.7Hz, 2H), 4.30 (q, J=7.1Hz, 2H), 1.18 (t, J=7.1Hz, 3H).
The synthesis of embodiment ten: 2,2-dibromo (4-oil of mirbane formyl) ethyl acetate
Using (4-oil of mirbane formyl) ethyl acetate, Sodium Bromide as raw material, its reactions steps is as follows:
(4-oil of mirbane formyl) ethyl acetate (0.237g, 1mmol), Sodium Bromide (0.206g, 2mmol), cupric iodide (0.064g, 0.2mmol), manganese acetate (1.89g, 7mmol) and ethanol (10 milliliters) is added, 60 DEG C of reactions in reaction flask;
tLC follows the tracks of reaction until terminate completely;
the crude by column chromatography obtained after reaction terminates is separated (ethyl acetate: sherwood oil=1:20), obtains target product (productive rate 65%).The analytical data of product is as follows:
1hNMR (400MHz, CDCl
3): δ 8.34 – 8.28 (m, 2H), 8.25 – 8.16 (m, 2H), 4.33 (q, J=7.1Hz, 2H), 1.21 (t, J=7.1Hz, 3H).
The synthesis of embodiment 11: 2,2-dibromo (3-Bromophenacyl) ethyl acetate
Using (3-Bromophenacyl) ethyl acetate, Sodium Bromide as raw material, its reactions steps is as follows:
(3-Bromophenacyl) ethyl acetate (0.269g, 1mmol), Sodium Bromide (0.206g, 2mmol), cuprous bromide (0.014g, 0.1mmol), manganese acetate (1.62g, 6mmol) and ethanol (10 milliliters) is added, 60 DEG C of reactions in reaction flask;
tLC follows the tracks of reaction until terminate completely;
the crude by column chromatography obtained after reaction terminates is separated (ethyl acetate: sherwood oil=1:20), obtains target product (productive rate 65%).The analytical data of product is as follows:
1hNMR (400MHz, CDCl
3): δ 8.16 (s, 1H), 7.92 (d, J=7.9Hz, 1H), 7.71 (d, J=8.0Hz, 1H), 7.33 (t, J=8.0Hz, 1H), 4.31 (q, J=7.1Hz, 2H), 1.19 (t, J=7.1Hz, 2H).
The synthesis of bromo-1, the 3-diphenylpropane-1，3-dione of embodiment 12: 2,2-bis-
With 1,3-diphenylpropane-1，3-dione, Sodium Bromide as raw material, its reactions steps is as follows:
1,3-diphenylpropane-1，3-dione (0.224g, 1mmol), Sodium Bromide (0.206g, 2mmol), cuprous bromide (0.014g, 0.1mmol), manganese acetate (1.89g, 7mmol) and acetic acid (10 milliliters) is added, 60 DEG C of reactions in reaction flask;
tLC follows the tracks of reaction until terminate completely;
the crude by column chromatography obtained after reaction terminates is separated (ethyl acetate: sherwood oil=1:20), obtains target product (productive rate 74%).The analytical data of product is as follows:
1hNMR (400MHz, CDCl
3): δ 8.06 – 7.82 (m, 4H), 7.52 – 7.46 (m, 2H), 7.41 – 7.31 (m, 4H).
The synthesis of chloro-1, the 3-diphenylpropane-1，3-dione of embodiment 13: 2,2-bis-
With 1,3-diphenylpropane-1，3-dione, sodium-chlor as raw material, its reactions steps is as follows:
1,3-diphenylpropane-1，3-dione (0.224g, 1mmol), sodium-chlor (0.116g, 2mmol), cuprous chloride (0.010g, 0.1mmol), manganese acetate (0.81g, 3mmol) and ethanol (10 milliliters) is added, 60 DEG C of reactions in reaction flask;
tLC follows the tracks of reaction until terminate completely;
the crude by column chromatography obtained after reaction terminates is separated (ethyl acetate: sherwood oil=1:20), obtains target product (productive rate 73%).The analytical data of product is as follows:
1hNMR (400MHz, CDCl
3): δ 8.06 – 7.82 (m, 4H), 7.52 – 7.46 (m, 2H), 7.41 – 7.31 (m, 4H).
The synthesis of bromo-3-phenyl-1, the 3-propanedione of embodiment 14: 1-(2-furyl)-2,2-bis-
With 1-(2-furyl)-3-phenyl-1,3-propanedione, Sodium Bromide as raw material, its reactions steps is as follows:
1-(2-furyl)-3-phenyl-1,3-propanedione (0.214g, 1mmol), Sodium Bromide (0.206g is added in reaction flask, 2mmol), cuprous bromide (0.014g, 0.1mmol), manganese acetate (1.89g, 7mmol) and acetic acid (10 milliliters), 60 DEG C of reactions;
tLC follows the tracks of reaction until terminate completely;
the crude by column chromatography obtained after reaction terminates is separated (ethyl acetate: sherwood oil=1:20), obtains target product (productive rate 74%).The analytical data of product is as follows:
1hNMR (400MHz, CDCl
3): δ 8.85 – 8.50 (m, 2H), 7.88 – 7.50 (m, 5H), 7.33 – 7.30 (m, 1H).
The synthesis of chloro-3-phenyl-1, the 3-propanedione of embodiment 15: 1-(2-furyl)-2,2-bis-
With 1-(2-furyl)-3-phenyl-1,3-propanedione, sodium-chlor as raw material, its reactions steps is as follows:
1-(2-furyl)-3-phenyl-1,3-propanedione (0.214g, 1mmol), sodium-chlor (0.116g is added in reaction flask, 2mmol), cuprous chloride (0.010g, 0.1mmol), manganese acetate (1.08g, 4mmol) and acetic acid (10 milliliters), 60 DEG C of reactions;
tLC follows the tracks of reaction until terminate completely;
the crude by column chromatography obtained after reaction terminates is separated (ethyl acetate: sherwood oil=1:20), obtains target product (productive rate 85%).The analytical data of product is as follows:
1hNMR (400MHz, CDCl
3): δ 8.85 – 8.50 (m, 2H), 7.88 – 7.50 (m, 5H), 7.33 – 7.30 (m, 1H).
The synthesis of bromo-3-phenyl-1, the 3-propanedione of embodiment 16: 1-(2-thienyl)-2,2-bis-
With 1-(2-thienyl)-3-phenyl-1,3-propanedione, Sodium Bromide as raw material, its reactions steps is as follows:
1-(2-thienyl)-3-phenyl-1,3-propanedione (0.230g, 1mmol), Sodium Bromide (0.206g is added in reaction flask, 2mmol), cuprous bromide (0.014g, 0.1mmol), manganese acetate (2.16g, 8mmol) and acetic acid (10 milliliters), 60 DEG C of reactions;
tLC follows the tracks of reaction until terminate completely;
the crude by column chromatography obtained after reaction terminates is separated (ethyl acetate: sherwood oil=1:20), obtains target product (productive rate 80%).The analytical data of product is as follows:
1hNMR (400MHz, CDCl
3): δ 8.15 – 7.90 (m, 4H), 7.88 – 7.50 (m, 3H), 7.33 – 7.20 (m, 1H).
The synthesis of bromo-3-phenyl-1, the 3-propanedione of embodiment 17: 1-(2-pyrryl)-2,2-bis-
With 1-(2-pyrryl)-3-phenyl-1,3-propanedione, Sodium Bromide as raw material, its reactions steps is as follows:
1-(2-pyrryl)-3-phenyl-1,3-propanedione (0.213g, 1mmol), Sodium Bromide (0.206g is added in reaction flask, 2mmol), cuprous bromide (0.014g, 0.1mmol), manganese acetate (1.89g, 7mmol) and acetic acid (10 milliliters), 60 DEG C of reactions;
tLC follows the tracks of reaction until terminate completely;
the crude by column chromatography obtained after reaction terminates is separated (ethyl acetate: sherwood oil=1:20), obtains target product (productive rate 78%).The analytical data of product is as follows:
1hNMR (400MHz, CDCl
3): δ 10.80 (s, 1H), 8.21 – 8.00 (m, 3H), 7.74 – 7.48 (m, 3H), 7.35 – 7.00 (m, 2H).
The bromo-1-(4-p-methoxy-phenyl of embodiment 18: 2,2-bis-) synthesis of-3-phenyl-1,3-propanedione
With 1-(4-p-methoxy-phenyl)-3-phenyl-1,3-propanedione, Sodium Bromide as raw material, its reactions steps is as follows:
in reaction flask, add 1-(4-p-methoxy-phenyl)-3-phenyl-1,3-propanedione (0.254g, 1mmol), Sodium Bromide (0.206g, 2mmol), cuprous bromide (0.014g, 0.1mmol), manganese acetate (1.89g, 7mmol) and dimethyl formamide (10 milliliters), 70 DEG C of reactions;
tLC follows the tracks of reaction until terminate completely;
the crude by column chromatography obtained after reaction terminates is separated (ethyl acetate: sherwood oil=1:20), obtains target product (productive rate 85%).The analytical data of product is as follows:
1hNMR (400MHz, CDCl
3): δ 7.97 – 7.87 (m, 4H), 7.46 (t, J=7.4Hz, 1H), 7.33 (t, J=7.9Hz, 2H), 6.83 – 6.67 (m, 2H), 3.78 (s, 3H).
The bromo-1-(2-aminomethyl phenyl of embodiment 19: 2,2-bis-) synthesis of-3-phenyl-1,3-propanedione
With 1-(2-aminomethyl phenyl)-3-phenyl-1,3-propanedione, Sodium Bromide as raw material, its reactions steps is as follows:
in reaction flask, add 1-(2-aminomethyl phenyl)-3-phenyl-1,3-propanedione (0.238g, 1mmol), Sodium Bromide (0.206g, 2mmol), cuprous bromide (0.014g, 0.1mmol), manganese acetate (1.89g, 7mmol) and dimethyl formamide (10 milliliters), 70 DEG C of reactions;
tLC follows the tracks of reaction until terminate completely;
the crude by column chromatography obtained after reaction terminates is separated (ethyl acetate: sherwood oil=1:20), obtains target product (productive rate 88%).The analytical data of product is as follows:
1hNMR (400MHz, CDCl
3): δ 7.97 – 7.93 (m, 2H), 7.78 (d, J=7.1Hz, 1H), 7.54 – 7.48 (m, 1H), 7.41 – 7.32 (m, 3H), 7.24 (d, J=7.7Hz, 1H), 7.13 (t, J=8.0Hz, 1H), 2.50 (s, 3H).
The synthesis of embodiment 20: 2,2-bromo-1,3-bis-(2-p-methoxy-phenyl)-1,3-propanedione
With 1,3-bis-(2-p-methoxy-phenyl)-1,3-propanedione, Sodium Bromide as raw material, its reactions steps is as follows:
1,3-bis-(2-p-methoxy-phenyl)-1,3-propanedione (0.284g is added in reaction flask, 1mmol), Sodium Bromide (0.206g, 2mmol), cuprous bromide (0.014g, 0.1mmol), manganese acetate (1.89g, 7mmol) with dimethyl formamide (10 milliliters), 70 DEG C of reactions;
tLC follows the tracks of reaction until terminate completely;
the crude by column chromatography obtained after reaction terminates is separated (ethyl acetate: sherwood oil=1:20), obtains target product (productive rate 89%).The analytical data of product is as follows:
1hNMR (400MHz, CDCl
3): δ 7.98 (dd, J=7.9,1.7Hz, 2H), 7.48 – 7.38 (m, 2H), 7.00 (t, J=7.9Hz, 2H), 6.79 (d, J=8.3Hz, 2H), 3.57 (s, 6H).
The synthesis of bromo-1-phenyl-1, the 3-diacetylmethane of embodiment 21: 2,2-bis-
With 1-phenyl-1,3-diacetylmethane, Sodium Bromide as raw material, its reactions steps is as follows:
1-phenyl-1,3-diacetylmethane (0.176g, 1mmol), Sodium Bromide (0.206g, 2mmol), cuprous bromide (0.014g, 0.1mmol), manganese acetate (1.89g, 7mmol) and acetic acid (10 milliliters) is added, 60 DEG C of reactions in reaction flask;
tLC follows the tracks of reaction until terminate completely;
the crude by column chromatography obtained after reaction terminates is separated (ethyl acetate: sherwood oil=1:20), obtains target product (productive rate 78%).The analytical data of product is as follows:
1hNMR (400MHz, CDCl
3): δ 8.09 – 7.95 (m, 2H), 7.61 – 7.55 (m, 1H), 7.45 (t, J=7.9Hz, 2H), 2.82 (q, J=7.2Hz, 2H), 1.16 (t, J=7.2Hz, 3H).
The bromo-1-(4-chloro-phenyl-of embodiment 22: 2,2-bis-) synthesis of-3-phenyl-1,3-propanedione
With 1-(4-chloro-phenyl-)-3-phenyl-1,3-propanedione, Sodium Bromide as raw material, its reactions steps is as follows:
in reaction flask, add 1-(4-chloro-phenyl-)-3-phenyl-1,3-propanedione (0.256g, 1mmol), Sodium Bromide (0.206g, 2mmol), cuprous bromide (0.014g, 0.1mmol), manganese acetate (1.89g, 7mmol) and acetonitrile (10 milliliters), 60 DEG C of reactions;
tLC follows the tracks of reaction until terminate completely;
the crude by column chromatography obtained after reaction terminates is separated (ethyl acetate: sherwood oil=1:20), obtains target product (productive rate 76%).The analytical data of product is as follows:
1hNMR (400MHz, CDCl
3): δ 7.95 (d, J=7.5Hz, 2H), 7.89 (d, J=8.7Hz, 2H), 7.52 (t, J=7.4Hz, 1H), 7.38 (t, J=7.8Hz, 2H), 7.33 (d, J=8.7Hz, 2H).
The bromo-1-(4-bromophenyl of embodiment 23: 2,2-bis-) synthesis of-3-phenyl-1,3-propanedione
With 1-(4-bromophenyl)-3-phenyl-1,3-propanedione, Sodium Bromide as raw material, its reactions steps is as follows:
in reaction flask, add 1-(4-bromophenyl)-3-phenyl-1,3-propanedione (0.301g, 1mmol), Sodium Bromide (0.206g, 2mmol), cuprous bromide (0.014g, 0.1mmol), manganese acetate (1.89g, 7mmol) and acetonitrile (10 milliliters), 60 DEG C of reactions;
tLC follows the tracks of reaction until terminate completely;
the crude by column chromatography obtained after reaction terminates is separated (ethyl acetate: sherwood oil=1:20), obtains target product (productive rate 80%).The analytical data of product is as follows:
1hNMR (400MHz, CDCl
3): δ 7.99 – 7.92 (m, 2H), 7.86 – 7.75 (m, 2H), 7.56 – 7.47 (m, 3H), 7.38 (t, J=7.8Hz, 2H).
The synthesis of the bromo-3-oxopentanoic acid methyl ester of embodiment 24: 2,2-bis-
Using 3-oxopentanoic acid methyl ester, Sodium Bromide as raw material, its reactions steps is as follows:
3-oxopentanoic acid methyl ester (0.144g, 1mmol), Sodium Bromide (0.206g, 2mmol), cuprous bromide (0.014g, 0.1mmol), manganese acetate (1.89g, 7mmol) and acetic acid (10 milliliters) is added, 60 DEG C of reactions in reaction flask;
tLC follows the tracks of reaction until terminate completely;
the crude by column chromatography obtained after reaction terminates is separated (ethyl acetate: sherwood oil=1:20), obtains target product (productive rate 64%).The analytical data of product is as follows:
1hNMR (400MHz, CDCl
3): δ 4.35 (q, J=7.1Hz, 2H), 2.94 (q, J=7.2Hz, 2H), 1.33 (t, J=7.1Hz, 3H), 1.21 (t, J=7.2Hz, 3H).
The synthesis of the chloro-3-oxopentanoic acid methyl ester of embodiment 25: 2,2-bis-
Using 3-oxopentanoic acid methyl ester, sodium-chlor as raw material, its reactions steps is as follows:
3-oxopentanoic acid methyl ester (0.144g, 1mmol), sodium-chlor (0.116g, 2mmol), cuprous chloride (0.010g, 0.1mmol), manganese acetate (1.08g, 4mmol) and acetic acid (10 milliliters) is added, 60 DEG C of reactions in reaction flask;
tLC follows the tracks of reaction until terminate completely;
the crude by column chromatography obtained after reaction terminates is separated (ethyl acetate: sherwood oil=1:20), obtains target product (productive rate 74%).The analytical data of product is as follows:
1hNMR (400MHz, CDCl
3): δ 4.35 (q, J=7.1Hz, 2H), 2.94 (q, J=7.2Hz, 2H), 1.33 (t, J=7.1Hz, 3H), 1.21 (t, J=7.2Hz, 3H).
The synthesis of bromo-1, the 3-diacetylmethane of embodiment 26: 3,3-bis-
With 1,3-diacetylmethane, Sodium Bromide as raw material, its reactions steps is as follows:
1,3-diacetylmethane (0.100g, 1mmol), Sodium Bromide (0.206g, 2mmol), cuprous bromide (0.014g, 0.1mmol), manganese acetate (1.89g, 7mmol) and acetic acid (10 milliliters) is added, 60 DEG C of reactions in reaction flask;
tLC follows the tracks of reaction until terminate completely;
the crude by column chromatography obtained after reaction terminates is separated (ethyl acetate: sherwood oil=1:20), obtains target product (productive rate 68%).The analytical data of product is as follows:
1hNMR (400MHz, CDCl
3): δ 2.60 (s, 6H).
The synthesis of bromo-3, the 5-heptadione of embodiment 27: 4,4-bis-
With 3,5-heptadione, Sodium Bromide as raw material, its reactions steps is as follows:
3,5-heptadione (0.128g, 1mmol), Sodium Bromide (0.206g, 2mmol), cuprous bromide (0.014g, 0.1mmol), manganese acetate (1.89g, 7mmol) and acetic acid (10 milliliters) is added, 60 DEG C of reactions in reaction flask;
tLC follows the tracks of reaction until terminate completely;
the crude by column chromatography obtained after reaction terminates is separated (ethyl acetate: sherwood oil=1:20), obtains target product (productive rate 65%).The analytical data of product is as follows:
1hNMR (400MHz, CDCl
3): δ 2.75 (q, J=7.2Hz, 4H), 1.23 (t, J=7.2Hz, 6H).
The synthesis of chloro-3, the 5-heptadione of embodiment 28: 4,4-bis-
With 3,5-heptadione, sodium-chlor as raw material, its reactions steps is as follows:
3,5-heptadione (0.128g, 1mmol), sodium-chlor (0.116g, 2mmol), cuprous chloride (0.010g, 0.1mmol), manganese acetate (1.08g, 4mmol) and acetic acid (10 milliliters) is added, 60 DEG C of reactions in reaction flask;
tLC follows the tracks of reaction until terminate completely;
the crude by column chromatography obtained after reaction terminates is separated (ethyl acetate: sherwood oil=1:20), obtains target product (productive rate 71%).The analytical data of product is as follows:
1hNMR (400MHz, CDCl
3): δ 2.75 (q, J=7.2Hz, 4H), 1.23 (t, J=7.2Hz, 6H).
The synthesis of embodiment 29: 2,2-dibromomalonic acid diethyl ester
Using diethyl malonate, Sodium Bromide as raw material, its reactions steps is as follows:
diethyl malonate (0.160g, 1mmol), Sodium Bromide (0.206g, 2mmol), cuprous bromide (0.014g, 0.1mmol), manganese acetate (1.89g, 7mmol) and acetic acid (10 milliliters) is added, 60 DEG C of reactions in reaction flask;
tLC follows the tracks of reaction until terminate completely;
the crude by column chromatography obtained after reaction terminates is separated (ethyl acetate: sherwood oil=1:20), obtains target product (productive rate 74%).The analytical data of product is as follows:
1hNMR (400MHz, CDCl
3): δ 4.75 (q, J=7.3Hz, 4H), 1.63 (t, J=7.3Hz, 6H).
The synthesis of embodiment 30: 2,2-dichloro diethyl malonate
Using diethyl malonate, sodium-chlor as raw material, its reactions steps is as follows:
diethyl malonate (0.160g, 1mmol), sodium-chlor (0.116g, 2mmol), cuprous chloride (0.010g, 0.1mmol) manganese acetate (1.08g, 4mmol) and acetic acid (10 milliliters) is added, 60 DEG C of reactions in reaction flask;
tLC follows the tracks of reaction until terminate completely;
the crude by column chromatography obtained after reaction terminates is separated (ethyl acetate: sherwood oil=1:20), obtains target product (productive rate 72%).The analytical data of product is as follows:
1hNMR (400MHz, CDCl
3): δ 4.75 (q, J=7.3Hz, 4H), 1.63 (t, J=7.3Hz, 6H).
The bromo-1-(4-aminomethyl phenyl of embodiment 31: 2,2-bis-) synthesis of-3-phenyl-1,3-propanedione
With 1-(4-aminomethyl phenyl)-3-phenyl-1,3-propanedione, Sodium Bromide as raw material, its reactions steps is as follows:
in reaction flask, add 1-(4-aminomethyl phenyl)-3-phenyl-1,3-propanedione (0.238g, 1mmol), Sodium Bromide (0.206g, 2mmol), cuprous bromide (0.014g, 0.1mmol), manganese acetate (1.89g, 7mmol) and ethanol (10 milliliters), 60 DEG C of reactions;
tLC follows the tracks of reaction until terminate completely;
steam solvent, residue with Ethyl acetate extracts 2 times, and residue remaining after extraction is used for testing next time; Merge secondary acetic acid ethyl acetate extract, steam ethyl acetate and obtain crude product, then through column chromatography for separation (ethyl acetate: sherwood oil=1:20), obtain target product (productive rate 86%).The analytical data of product is as follows:
1hNMR (400MHz, CDCl
3): δ 7.92 (d, J=7.5Hz, 2H), 7.83 (d, J=8.3Hz, 2H), 7.43 (t, J=7.4Hz, 1H), 7.30 (t, J=7.8Hz, 2H), 7.10 (d, J=8.2Hz, 2H), 2.28 (s, 3H).
The bromo-1-(4-aminomethyl phenyl of embodiment 32: 2,2-bis-) synthesis of-3-phenyl-1,3-propanedione
in embodiment 31 reactions steps
in add 1-(4-aminomethyl phenyl in the residue that is left afterwards of the extraction that obtains)-3-phenyl-1,3-propanedione (0.238g, 1mmol), Sodium Bromide (0.206g, 2mmol), manganese acetate (0.54g, 2mmol) and ethanol (10 milliliters), 60 DEG C of reactions;
tLC follows the tracks of reaction until terminate completely;
steam solvent, residue with Ethyl acetate extracts 2 times, and residue remaining after extraction is used for testing next time; Merge secondary acetic acid ethyl acetate extract, steam ethyl acetate and obtain crude product, then through column chromatography for separation (ethyl acetate: sherwood oil=1:20), obtain target product (productive rate 80%).
Catalyzer cuprous bromide in the present invention's reaction and the manganese acetate be not consumed in reacting can be continued to utilize by second time reaction, do not need during subsequent reactions to add catalyzer cuprous bromide again, as long as add proper amount of acetic acid manganese, add other reactant and solvent, thus the recycling of resource can be realized, reach economize on resources, the object of decreasing pollution.
Claims (10)
1. the preparation method of dihalo-1, a 3-Dicarbonyl derivatives, is characterized in that, comprise the following steps: 1,3-Dicarbonyl derivatives, sodium-chlor, manganese acetate and copper catalyst are added in solvent, react at 30 ~ 90 DEG C, obtain 2,2-dihalo-1,3-Dicarbonyl derivatives;
Described 1,3-Dicarbonyl derivatives is as shown in following chemical structure of general formula:
Wherein R
1be selected from: the one in alkyl, aryl, heteroaryl or alkoxyl group; R
2be selected from: the one in alkyl, aryl, heteroaryl or alkoxyl group;
The chemical formula of described copper catalyst is CuX
n, wherein X is Cl or Br; N is 1 or 2;
Described solvent is selected from: the one in methyl alcohol, ethanol, ethylene glycol, acetonitrile, acetic acid, propionic acid, dimethyl formamide;
Described 2,2-dihalo-1,3-Dicarbonyl derivatives are as shown in following chemical structure of general formula:
。
2. the preparation method of 2,2-dihalo-1,3-Dicarbonyl derivatives according to claim 1, is characterized in that: in molar ratio, 1,3-Dicarbonyl derivatives: sodium-chlor: manganese acetate: copper catalyst is 1: 2: (2 ~ 8): (0.08 ~ 0.12).
3. the preparation method of 2,2-dihalo-1,3-Dicarbonyl derivatives according to claim 2, is characterized in that: in molar ratio, 1,3-Dicarbonyl derivatives: manganese acetate: copper catalyst is 1: 4: 0.1.
4. the preparation method of 2,2-dihalo-1,3-Dicarbonyl derivatives according to claim 1, is characterized in that: described 1,3-Dicarbonyl derivatives is selected from ethyl benzoylacetate, (4-toluyl) ethyl acetate, (4-methoxybenzoyl) ethyl acetate, (2-toluyl) ethyl acetate, (2-methoxybenzoyl) ethyl acetate, naphthoyl ethyl acetate, (4-chlorobenzoyl) ethyl acetate, (4-Bromophenacyl) ethyl acetate, (4-oil of mirbane formyl) ethyl acetate, (3-Bromophenacyl) ethyl acetate, 1,3-diphenylpropane-1，3-dione, 1-(2-furyl)-3-phenyl-1,3-propanedione, 1-(2-thienyl)-3-phenyl-1,3-propanedione, 1-(2-pyrryl)-3-phenyl-1,3-propanedione, 1-(4-aminomethyl phenyl)-3-phenyl-1,3-propanedione, 1-(4-p-methoxy-phenyl)-3-phenyl-1,3-propanedione, 1-(2-aminomethyl phenyl)-3-phenyl-1,3-propanedione, 1,3-bis-(2-p-methoxy-phenyl)-1,3-propanedione, 1-phenyl-1,3-diacetylmethane, 1-(4-chloro-phenyl-)-3-phenyl-1,3-propanedione, 1-(4-bromophenyl)-3-phenyl-1,3-propanedione, 3-oxopentanoic acid methyl ester, 1,3-diacetylmethane, 3,5-heptadione, one in diethyl malonate.
5. the preparation method of 2,2-dihalo-1,3-Dicarbonyl derivatives according to claim 1, is characterized in that: described reaction is carried out in atmosphere; Thin-layer chromatography is utilized to follow the tracks of reaction until terminate completely; Reaction terminates to carry out column chromatography for separation purification processes to product afterwards.
6. the preparation method of dihalo-1, a 3-Dicarbonyl derivatives, is characterized in that, comprise the following steps: 1,3-Dicarbonyl derivatives, Sodium Bromide, manganese acetate and copper catalyst are added in solvent, react at 30 ~ 90 DEG C, obtain 2,2-dihalo-1,3-Dicarbonyl derivatives;
In molar ratio, 1,3-Dicarbonyl derivatives: Sodium Bromide: manganese acetate: copper catalyst is 1: 2: (6 ~ 8): (0.08 ~ 0.12);
Described 1,3-Dicarbonyl derivatives is as shown in following chemical structure of general formula:
Wherein R
1be selected from: the one in alkyl, aryl, heteroaryl or alkoxyl group; R
2be selected from: the one in alkyl, aryl, heteroaryl or alkoxyl group;
The chemical formula of described copper catalyst is CuX
n, wherein X is Cl or Br; N is 1 or 2;
Described solvent is selected from: the one in methyl alcohol, ethanol, ethylene glycol, acetonitrile, acetic acid, propionic acid, dimethyl formamide;
Described 2,2-dihalo-1,3-Dicarbonyl derivatives are as shown in following chemical structure of general formula:
。
7. the preparation method of 2,2-dihalo-1,3-Dicarbonyl derivatives according to claim 6, is characterized in that: described 1,3-Dicarbonyl derivatives is selected from ethyl benzoylacetate, (4-toluyl) ethyl acetate, (4-methoxybenzoyl) ethyl acetate, (2-toluyl) ethyl acetate, (2-methoxybenzoyl) ethyl acetate, naphthoyl ethyl acetate, (4-chlorobenzoyl) ethyl acetate, (4-Bromophenacyl) ethyl acetate, (4-oil of mirbane formyl) ethyl acetate, (3-Bromophenacyl) ethyl acetate, 1,3-diphenylpropane-1，3-dione, 1-(2-furyl)-3-phenyl-1,3-propanedione, 1-(2-thienyl)-3-phenyl-1,3-propanedione, 1-(2-pyrryl)-3-phenyl-1,3-propanedione, 1-(4-aminomethyl phenyl)-3-phenyl-1,3-propanedione, 1-(4-p-methoxy-phenyl)-3-phenyl-1,3-propanedione, 1-(2-aminomethyl phenyl)-3-phenyl-1,3-propanedione, 1,3-bis-(2-p-methoxy-phenyl)-1,3-propanedione, 1-phenyl-1,3-diacetylmethane, 1-(4-chloro-phenyl-)-3-phenyl-1,3-propanedione, 1-(4-bromophenyl)-3-phenyl-1,3-propanedione, 3-oxopentanoic acid methyl ester, 1,3-diacetylmethane, 3,5-heptadione, one in diethyl malonate.
8. the preparation method of 2,2-dihalo-1,3-Dicarbonyl derivatives according to claim 6, is characterized in that: described reaction is carried out in atmosphere; Thin-layer chromatography is utilized to follow the tracks of reaction until terminate completely; Reaction terminates to carry out column chromatography for separation purification processes to product afterwards.
9. the preparation method of 2,2-dihalo-1,3-Dicarbonyl derivatives according to claim 6, is characterized in that: in molar ratio, 1,3-Dicarbonyl derivatives: manganese acetate: copper catalyst is 1: 7: 0.1.
10. the preparation method of 2,2-dihalo-1,3-Dicarbonyl derivatives according to claim 6, is characterized in that: described temperature of reaction is 60 ~ 70 DEG C.
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| WO2017100985A1 (en) * | 2015-12-14 | 2017-06-22 | 苏州大学张家港工业技术研究院 | Preparation method for 2,2-dihalo-1,3-dicarbonyl derivatives |
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