CN106565535B - The preparation method of 2- diazonium -1- aryl ketones compounds - Google Patents
The preparation method of 2- diazonium -1- aryl ketones compounds Download PDFInfo
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C245/00—Compounds containing chains of at least two nitrogen atoms with at least one nitrogen-to-nitrogen multiple bond
- C07C245/12—Diazo compounds, i.e. compounds having the free valencies of >N2 groups attached to the same carbon atom
- C07C245/14—Diazo compounds, i.e. compounds having the free valencies of >N2 groups attached to the same carbon atom having diazo groups bound to acyclic carbon atoms of a carbon skeleton
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Abstract
The present invention provides a kind of preparation method of synthesis 2 diazonium, 1 aryl ketones.Using beta-dicarbonyl compound, p-toluene sulfonyt azide and methylamine as raw material, it is not necessarily to catalyst and alkali under room temperature, so that it may with 2 diazonium of generation, 1 aryl ketones compounds rapidly and efficiently.Compared with prior art, simple and safe operation avoids the diazotation step of operational hazards to this method.Reaction condition of the present invention is mild, rapidly and efficiently, provides a kind of completely new, more easily method for the preparation of α diazonium carbonyls, can be applied to the fields such as chemical medicine, biology, material.
Description
Technical field
The invention belongs to chemical field, specially design one kind is by beta-dicarbonyl compound, nitrine and aminated compounds
Raw material, the method for rapidly and efficiently generating 2- diazonium -1- aryl ketones compounds under room temperature.
Background technology
The report for the first time of α-diazonium carbonyls be Curtius in 1883 by glycine diazo compounds at.Although
It is found that later in Wolff in 1912 and is named after one's own name the rearrangement reaction of α-diazonium carbonyls, but α-diazonium
The primary synthetic methods of carbonyls be then nineteen twenty-eight by Arndt and Eistert propose by acyl chlorides and diazomethane come
It obtains.Although by the development in century more than one, scientists propose the side of various synthesis α-diazonium carbonyls
Method, but the small synthetic agent of dangerous development property coefficient and efficiently simple synthetic method are still needed.It is main at present
Synthetic method have：I, diazonium paraffin is acylated；II, diazo transfer reaction；The decomposition of III, hydrazone and p-toluenesulfonyl hydrazone；
The diazotising of IV, amine；V, the decomposition of triazenes；VI, cross-coupling is carried out to existing diazonium carbonyls or it is taken
Modification and some other synthetic method are carried out for base.Wherein the decomposition of triazenes due to substrate applicability it is extremely limited, and weigh
The reaction condition and type of nitridation reaction have no prodigious progress in recent years.
I, diazonium paraffin is acylated
Diazonium paraffin is acylated the end diazonium carbonyls of main synthesis non-annularity.The synthetic method be nineteen twenty-eight by
What Arndt and Eistert was proposed prepares diazonium carbonyls by acyl chlorides and diazomethane.Although utilizing diazonium paraffin acyl
The method of base can prepare different types of diazonium carbonyls, but this method can not break away from the use of diazomethane.Weight
The low boiling point (bp-23 DEG C) of n-formyl sarcolysine alkane, toxicity is big, easily decomposes, and explosion is easy in preparation and use, to make it big
Amount produces and is encountered in obstacle.Its alternative compounds trimethyl silicane base diazomethane price is more expensive and volatile,
Toxicity also limits greatly its large-scale use.
II, diazo transfer reaction
Diazo transfer reaction is mainly used in the compound containing wave methylene living, such as carbonyls and carboxylic acid derivates
Deng.Reaction carries out diazo transfer under alkaline condition by sulfonyl nitrine, is found by Retigz and is reported, therefore also referred to as
(Fig. 1) is reacted for Retigz diazo transfers.It is then needed in strong basicity when this method is applied to simple ketone or ester type compound
Under the conditions of it is preactivated at dicarbonyl compound, the use of highly basic reduces the compatibility of functional group.
The decomposition of III, hydrazone
When diazonium functional groups are not stablized by neighbouring carbonyl, which is unstable.Can not at this time yet
It is acylated by diazonium paraffin and is realized with diazo transfer.In addition the decomposition reaction of hydrazone there is also some problems：It (1) will be first by carbonyl
Base class compound is converted into hydrazone, but some carbonyl complexs are hardly produced corresponding hydrazone, and hydrazone is unstable at room temperature.
(2) hydrazone is oxidized to weight nitrogen compound under the action of oxidant, not only operating condition largely needs low temperature, exists excessively
The problem of oxidation, and the compatibility of substrate reduces, therefore certain limitation is received in application aspect.
IV, some other synthetic method
Or using some special reagents or using costliness in the preparation method of other synthesis diazonium carbonyls
The condition of transition-metal catalyst, reaction is not mild enough, therefore is difficult the universal method as synthesis α-diazonium carbonyls.
In conclusion the novel processing step of α-diazonium carbonyls is still the major issue for needing to solve.
Invention content
Above-mentioned to solve the problems, such as, it is original that the present invention, which is provided by beta-dicarbonyl compound, nitrine and aminated compounds,
Material, the method for rapidly and efficiently generating 2- diazonium -1- aryl ketones compounds under room temperature, to overcome benzoyl in the prior art
The defects of amine preparation process is cumbersome, severe reaction conditions.
The present invention adopts the following technical scheme that realization：
A kind of preparation method of 2- diazonium -1- aryl ketones compounds, aminated compounds is added to dissolved with beta-dicarbonyl
In the solvent of compound, nitrine is added, is reacted 0.5~10 hour at 20~80 DEG C, reaction terminates, and water is added into system
Reaction is quenched, dichloromethane extraction is used in combination three times, merges organic phase, it is dry, solvent is removed, and carry out pillar layer separation, obtained
Finished product 2- diazonium -1- aryl ketones compounds.
Wherein the method for the present invention mainly generates 2- diazonium -1- aryl ketones compounds, and structural formula is：
R is substituted benzene ring or aromatic heterocycle group with armaticity in above formula.
Further, the beta-dicarbonyl compound structural formula is：
R can be aliphatic or aromatic group in above formula.
Further, the azide compounds structural formula is：
R in above formula1It can be with Ts, Ms, Ph.
Further, the aminated compounds structural formula is：
R in above formula2Can be hydrogen, aliphatic or aromatic group, R3Can be hydrogen, aliphatic or aromatic group.
Further, the molar ratio of the beta-dicarbonyl compound, aminated compounds and nitrine is 1:0.2~2.0:0.2
~2.0, mol/mol.
Further, the solvent be dichloromethane, tetrahydrofuran, toluene, ethyl acetate, NMP, DMSO, DMF, water, 1,
4- dioxane.
Further, the mass volume ratio of the beta-dicarbonyl compound and solvent is 1:2~20, g/mL.The present invention reacts
Equation is：
R can be aliphatic or aromatic group, R in above formula1Can be-Ms ,-Ts ,-Ph, R2Can be hydrogen, fat
Race or aromatic group, R3Can be hydrogen, aliphatic or aromatic group.
The acquisition process of the method for the present invention is as follows：
In recent years, the C-C key cracking reactions of 1,3- dicarbonyl compounds are answered extensively as a kind of novel, effective method
For in the synthesis of organic matter.It was found that by 1,3- diphenyl -1,3- propanedione, p-toluene sulfonyt azide (TsN3) and benzylamine, letter
Single ground stirs in a solvent, and 2- diazonium -1- Phenyl ethyl ketones can be obtained with almost quantitative yield.The experimental results showed that utilizing this
A kind of method of sample can efficiently prepare 2- diazonium -1- aryl ketones compounds under the conditions of comparatively gentle.Document tune
Display is ground, has a small amount of report to prepare 2- diazonium -1- aryl ketones using the C-C bond cleavages solution of 1,3- dicarbonyl compounds, but it is sharp
With 1,3- diketone, nitrine and three component of aminated compounds prepare the report of 2- diazonium -1- aryl ketones almost without, therefore the present invention
A kind of method efficiently synthesizing 2- diazonium -1- aryl ketones using 1,3- diketone, nitrine and three component of aminated compounds is provided.
Further the experimental results showed that, 2- diazonium -1,3- diphenyl -1,3- propanedione is the intermediate of the reaction, profit
2- diazonium -1,3- diphenyl -1,3- propanedione, which is used, as raw material can equally prepare almost quantitative 2- diazonium -1- phenyl second
Ketone.This shows that reaction is a two step cascade reactions, undergoes the reaction of Regitz diazo transfers, following 2- diazonium -1,3- first
The fracture of the C-C keys of diphenyl -1,3- propanedione.When changing benzylamine into n-butylamine, reaction can be good at carrying out, if but changing
At (n-Bu)2NH (dibutylamine) and (n-Bu)3When N (tri-butylamine), reaction only rests on 2- diazonium -1,3- diphenyl -1,3-
Propanedione stage, the cleavage reaction without carrying out C-C keys.It is therefore proposed that primary amine plays the role of both sides in the reaction：
Play the role of alkali in the reaction of Regitz diazo transfers；Play the role of reactant in the cleavage reaction of C-C keys.
After having certain understanding to reaction mechanism, next the solvent of reaction is screened.As shown in Table 1, the reaction
It can be adapted for almost all of solvent, but reaction rate significantly improves in some water-soluble solvents.
1 reaction dissolvent of table screens
Finally, the universality of reaction is explored.As seen from Figure 2, which has good substrate universality.
Stereoeffect has significant impact, substrate of the ortho position with substituent group to need longer reaction time, and yield reaction
It can decrease；And it is not apparent on the influence of the efficiency of reaction for the electronic effect on aromatic rings.In addition, the reaction may be used also
To prepare a series of diazonium products with heterocycle.
Therefore, the preparation method of synthesis 2- diazonium -1- aryl ketones of the present invention, with beta-dicarbonyl compound, to toluene
Sulfonyl azide and methylamine are raw material, are not necessarily to catalyst and alkali under room temperature, so that it may with generation 2- diazonium -1- virtues rapidly and efficiently
Base ketone compounds.This method simple and safe operation avoids the diazotation step of operational hazards.
The present invention having the beneficial effect that compared with the prior art：
1, this method carries out in neutral conditions, avoids limitation of traditional alkaline condition to reaction substrate.The party
Method is big without using toxicity, easily decompose and the diazomethane of explosive can be obtained by target compound, this is also most apparent
Advantage.
2, this method does not need metallic catalyst, and reaction condition is mild, and reaction efficiency is high, operation is simple, is α-weight
The preparation of nitrone compound provides a kind of completely new, more easily method, can be applied to chemical medicine, biology, material etc.
Field.
Description of the drawings
Fig. 1 shows the reactions of Retigz diazo transfers.
Fig. 2 indicates substrate universality.
Specific implementation mode
Below by specific embodiment to further instruction of the present invention, but embodiment is not intended to limit the protection model of the present invention
It encloses.
Embodiment 1
The preparation method of 2- diazonium -1- aromatic radical ethyl ketones is as follows：
Structural formula is：
R is F, Cl, Br, I, CH in formula3, OCH3, CN, tBu.
Preparation flow：1.0mmol beta-dicarbonyl compounds are sequentially added in the reaction bulb equipped with stirrer, to toluene sulphur
Sour nitrine (197.2mg, 1mmol) and EtOH (1mL), are then added CH into system again3NH2(93.2mg, 1.2mmol),
It is reacted 2.0 hours at 20-80 DEG C, reaction terminates, and water quenching is added into system and goes out reaction, dichloromethane extraction is used in combination three times, conjunction
And organic phase, it is dry, solvent is removed, and carry out pillar layer separation, obtains α-diazonium carbonyls that purity is 99%.
Embodiment 2
The preparation method of 2- diazonium -1- (3,4,5- trimethoxyphenyls) ethyl ketone is as follows：
Structural formula is：
Preparation flow：1,3- bis- (3,4,5- trimethoxyphenyls) third is sequentially added in the reaction bulb equipped with stirrer
Alkane -1,3- diketone (404mg, 1.0mmol), p-methyl benzenesulfonic acid nitrine (197mg, 1.0mmol) and EtOH (1mL), then again to
CH is added in system3NH2(93.2mg, 1.2mmol) reacts 2.0 hours at room temperature, and reaction terminates, and water quenching is added into system
It goes out reaction, dichloromethane extraction is used in combination three times, merge organic phase, it is dry, solvent is removed, and carry out pillar layer separation, obtained pure
2- diazonium -1- (3,4,5- trimethoxyphenyl) ethyl ketone (215mg, 91%) that degree is 99%.
Embodiment 3
The preparation method of 2- diazonium -1- (naphthalene -1- bases) ethyl ketone is as follows：
Structural formula is：
Preparation flow：Sequentially added in the reaction bulb equipped with stirrer 1,3- naphthalene propane -1,3- diketone (324mg,
1.0mmol), methylsulphur acyl azide (122mg, 1.0mmol) and EtOH (1mL), are then added CH into system again3NH2(93.2mg,
1.2mmol), it is reacted 1.0 hours at 50 DEG C, reaction terminates, and water quenching is added into system and goes out reaction, dichloromethane is used in combination to extract
Three times, merge organic phase, it is dry, solvent is removed, and carry out pillar layer separation, obtains the 2- diazonium -1- (naphthalenes-that purity is 98%
1- yls) ethyl ketone (171mg, 87%).
Embodiment 4
The preparation method of 2- diazonium -1- (naphthalene -2- bases) ethyl ketone is as follows：
Structural formula is：
Preparation flow：Sequentially added in the reaction bulb equipped with stirrer 1,3- naphthalene propane -1,3- diketone (324mg,
1.0mmol), methylsulphur acyl azide (122mg, 1.0mmol) and DMF (1mL), are then added BnNH into system again2(128.5mg,
1.2mmol), it is reacted 1.0 hours at 50 DEG C, reaction terminates, and water quenching is added into system and goes out reaction, dichloromethane is used in combination to extract
Three times, merge organic phase, it is dry, solvent is removed, and carry out pillar layer separation, obtains the 2- diazonium -1- (naphthalenes-that purity is 98%
2- yls) ethyl ketone (192mg, 98%).
Embodiment 5
The preparation method of 2- diazonium -1- (1H- pyrroles -2- bases) ethyl ketone is as follows：
Structural formula is：
Preparation flow：Bis- (1H- pyrroles -2- bases) propane -1,3- of 1,3- are sequentially added in the reaction bulb equipped with stirrer
Diketone (1.0mmol, 202mg), aziminobenzene (1.0mmol, 119mg) and EtOH (1mL), are then added n- into system again
BuNH2(87.6mg, 1.2mmol) reacts 1.0 hours at room temperature, and reaction terminates, and water quenching is added into system and goes out reaction, and
Three times with dichloromethane extraction, merge organic phase, it is dry, solvent is removed, and carry out pillar layer separation, it is 99% to obtain purity
2- diazonium -1- (1H- pyrroles -2- bases) ethyl ketone (122mg, 90%).
It should be noted that the above examples are only used to illustrate the technical scheme of the present invention and are not limiting, although with reference to compared with
Invention is explained in detail for good embodiment, it will be understood by those of ordinary skill in the art that, it can be to the skill of invention
Art scheme is modified or replaced equivalently, and without departing from the range of benzene inventive technique scheme, should all be covered the present invention's
In right.
Claims (3)
1. a kind of preparation method of 2- diazonium -1- aryl ketones compounds, it is characterised in that：By aminated compounds be added to dissolved with
In the solvent of beta-dicarbonyl compound, azide compounds are added, are reacted 0.5-10 hours at 20-80 DEG C, reaction terminates,
Water quenching is added into system to go out reaction, dichloromethane extraction is used in combination three times, merges organic phase, dry, removing solvent, and carry out column
Chromatographic isolation obtains finished product 2- diazonium -1- aryl ketones compounds；
The beta-dicarbonyl compound structural formula is：
R is hydrogen, aliphatic or aromatic group in above formula；
The azide compounds are benzenesulfonyl azide, methylsulphur acyl azide or aziminobenzene；
The aminated compounds is primary amine compound；
The molar ratio of the beta-dicarbonyl compound, aminated compounds and azido compound is 1:0.2~2.0:0.2~2.0.
2. the preparation method of 2- diazonium -1- aryl ketones compounds according to claim 1, it is characterised in that：It is described molten
Agent is dichloromethane, tetrahydrofuran, toluene, ethyl acetate, NMP, DMSO, DMF, water or 1,4- dioxane.
3. the preparation method of 2- diazonium -1- aryl ketones compounds according to claim 2, it is characterised in that：The β-
The mass volume ratio of dicarbonyl compound and solvent is 1:2~20.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN86102077A (en) * | 1985-04-22 | 1987-01-28 | 布里斯托尔-米尔斯公司 | Carbonization penem intermediates preparation |
| EP0799716A2 (en) * | 1996-04-03 | 1997-10-08 | Minnesota Mining And Manufacturing Company | Diazo compounds for laser-induced mass transfer imaging materials |
| CN105906529A (en) * | 2016-06-07 | 2016-08-31 | 江西富祥药业股份有限公司 | 4-halogenated-2-diazo-3-oxo-valeric acid(4-nitrobenzene)methyl ester and preparation method thereof |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3963523B2 (en) * | 1997-04-25 | 2007-08-22 | 日本曹達株式会社 | Method for producing diazo compound |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN86102077A (en) * | 1985-04-22 | 1987-01-28 | 布里斯托尔-米尔斯公司 | Carbonization penem intermediates preparation |
| EP0799716A2 (en) * | 1996-04-03 | 1997-10-08 | Minnesota Mining And Manufacturing Company | Diazo compounds for laser-induced mass transfer imaging materials |
| CN105906529A (en) * | 2016-06-07 | 2016-08-31 | 江西富祥药业股份有限公司 | 4-halogenated-2-diazo-3-oxo-valeric acid(4-nitrobenzene)methyl ester and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| Direct Introduction of the Diazo Function in Organic Synthesis;Hendrickson, James B.；Wolf, Walter A.;《Journal of Organic Chemistry》;19681231;第33卷(第9期);第3610-18页 * |
| Product class 21: diazo compounds;Heydt, H.;《Science of Synthesis》;20041231;第24卷;第843-935页 * |
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