Reagent and method for the introduction of substituted deformational group in connection with at least one electrophilic function

 

(57) Abstract:

Describes a reagent for introducing a substituted deformational group, in particular triptoreline, electrophilic compound containing an electrophilic atom selected from atoms of carbon, sulfur, selenium or tellurium, characterized in that it contains a) percarbonate acid of the formula EA-CF2-COOH, where EA represents an electron-withdrawing atom or group selected from the electrophilic groups that have constant Gametepat least equal to 0.1, and percarbonate acid is converted into a salt with a mineral or organic cation, b) an aprotic polar solvent, and the molar content of the released protons, which are these different components, including impurities is not more than half of the original molar concentration percarbonic acid. Also describes how to peralkaline, in particular perftoruglerodnye electrophilic compounds containing an atom selected from carbon, sulfur, selenium or tellurium. 2 C. and 21 C.p. f-crystals.

The invention relates to a reagent and method for the introduction of substituted deformational group in connection with at least one nucleophilic substitution or accession, usually carried out with various ORGANOMETALLIC derivatives.

Methods perftoruglerodnye or similar processes are usually based on the use of derived type perforability and are carried out in the presence of zinc. However, such methods are expensive because they require installation for processing of metal waste and removal of zinc, as zinc is the main agent, polluting the river.

Other methods in which perferably radical does not form a stable intermediate product ORGANOMETALLIC type, usually difficult to implement because of the very low stability of free performanceeasy anions in the reaction media. These anions usually lead to products karbonovogo type by the loss of one of his deputies.

The present invention is to develop a reagent that would allow perftoruglerodnye the mechanism for introduction of a carbanion without the use of ORGANOMETALLIC compounds of transition metals, such as zinc.

It was proposed to use as the source performanceline radicals, in particular, trivet carboxyl fragment and release of carbon dioxide. However, the results achieved were very mediocre, and used catalytic system is very complex. In addition, performanceline radicals or their equivalents, derived from the decomposition of these perfluoroine carbonic acids are unstable in the reaction environment and require the use of stabilizing agents.

Article J. Stahly in the Journal of Jlurine Chemistry, 45 (1989), 431-433 and U.S. patent 4990699 reported that thermal decomposition performancenow acids in the presence of aromatic compounds, such as 1,3,5-trinitrobenzene, leads to the formation of triptoreline anions CF3-that is confirmed by the formation of the complex of Meisenheimer. The complex can then be converted by oxidation into performanceline derivative of the corresponding aromatic compounds.

However, the need to carry out this oxidation makes this method perftoruglerodnye aromatic derivatives unpromising.

The present invention eliminates the disadvantages of the known methods using chemical, non-polluting and can lead to the target products with a satisfactory output.

Research related to this the image is of a catalyst and without an agent stabilizing mentioned intermediate products produced during decomposition of various perfluoroine carbonic acid.

It turned out that for the implementation of the decomposition percarbonic acids requires two main conditions: first, the choice of solvent, and the second is the content of impurities in the mixture constituting the reagent according to the present invention. In particular, it shows absolutely critical role in the content of labile hydrogen in the system, more specifically, the released protons, the content of which should be below the content of fluorine-containing groups selected by decomposition of salts percarbonic acids. Under labile hydrogen or released proton understand a hydrogen atom, capable of breaking away under the action of a strong base, in the form of a proton. Practically it comes to the protons of the acid functions, which have a pKa below about 20 (the term "about" means that the number 20 is only an indicative figure).

The above objectives are achieved using the proposed nucleophilic reagent attaching smeshannuyu deformational group to the compound containing at least one electrophilic function, and the specified reagent by soderzhimom, located, at least partially, in the form of salts with organic or mineral cation, and

b) an aprotic polar solvent:

when the content in the reagent protons released from its various components, including its impurities,

not more than half the original molar concentration specified percarbonic acid.

Electrophilic function of substrate capable of reacting with the reagent of the present invention, are functions that are typically react with ORGANOMETALLIC compounds, and more detail will be described below.

The smaller the content of selected protons in the reagent, the lower the risk of adverse reactions and the higher the output.

Thus, preferably, the reagent content of labile hydrogen atoms were not more than 10%, preferably 1% (mole.) in relation to the original content percarbonic acid.

The main impurity, bearing a labile hydrogen atoms is usually water, which can release up to two hydrogen atoms on the molecule.

Usually, I prefer to use substantially digidrirovannye reagents and solvents to the mass content is bdih reaction conditions such water content may be satisfactory, but in some cases it is desirable to operate at lower water concentrations, for example about 1 to 10000.

However, it is not necessary to remove all the water, as may be appropriate molar ratio water/percarbonate acid below 10%.

In addition, it was shown that other elements, transition metal elements having two stable valence state, such as copper, can be adverse reactions and can even be harmful.

Although the reagent according to the invention does not require the use of a catalyst, transition metals may be present as impurities introduced, for example, a solvent.

Therefore, it is preferable that the molar content of these elements was below 1000, mostly below 100, preferably below 10 ppm with respect to the original content percarbonic acid.

It was found that despite the fact that many times it was recommended to use with perforaciones acid elements of group VIII of the periodic system of elements for activating certain substrates and some types of reactions, it was discovered that these elements are especially harmful for the above reactivos group, which includes platinum, osmium, iridium, palladium, rhodium and ruthenium.

In the present description reference is made to the Supplement to the Bulletin of the Chemical Society of France, number 1, January, 1966, published in the periodical system of elements.

Thus, it is preferable that the content of platinum group metals, namely metals of group VIII, was below 100 ppm, mostly below 10 ppm, preferably below 1 ppm. These values are relative to the original percarbonic acid and is expressed in moles.

In General and based on empirical experience suggests that these two types of metals, namely transition metals with two valence States and metals of group VIII, must be in the reagent at the level of the total concentration of not more than 1000 molar ppm, preferably not more than 10 molar ppm.

It should be noted that the various metals that are present at a total concentration of the specified order, represent a very small number, and in this respect they do not play a catalytic role. Their presence does not improve the kinetics of the reaction, moreover, they are even harmful, if you are in too great quantity.

In addition to the above components pointed to by the given systems of reagents, using the fluorine-containing carboxylate, is not harmful, but it was of little interest due to the fact that you get a difficult-to-cut salt affluent.

However, it should be noted that the presence of fluorides in the environment tends to limit the turning percarbonic acid, but at the same time and reduces adverse reactions.

This effect will be more significant if the counterion of the fluoride will be three-dimensional. Cations that may be acceptable cations are alkali metal higher number than that of sodium, in particular potassium or cesium, or ions of type onievyh", namely the cations formed by the elements of column VB and VIB (such as defined in the periodic table istemi elements, published in the Supplement to the Bulletin of the Chemical society of France, January, 1966), connected with 4 or 3 hydrocarbon chains.

Among niewyk" cations originating from the elements of column V, the preferred reagents are tetraalkyl or tetraamine or phosphonium. The hydrocarbon group contains mostly 4-12 carbon atoms, preferably 4-8 carbon atoms. Onevia cations originating from the elements of the column VIV, predpochtitelnei, as identified above, the content of fluoride ions is a parameter that should be taken into account. Sometimes, it is preferable to limit the content, in particular, their original content in order to facilitate the final treatment of the reaction medium.

So, it is advisable that the content of fluoride, which has an ionic character, i.e. is able to ionize in the polarizing environment reagent, did not exceed the initial molar concentration of salt percarbonate acid, preferably half, more preferably a quarter.

So, as mentioned above, the solvent plays an important role in the present invention, it should be aprotic, mainly polar, and contain very few impurities, bearing an acidic hydrogen.

Therefore, it is preferable to use an aprotic polar solvent had a significant dipole moment. So, it is advisable that its relative dielectric constant (Epsilon) was not less than about 5 (the boundaries of the intervals are not considered as nachusa figures in the present description, unless otherwise specified). Preferably less than or equal to 50 and greater than or equal to 5, in particular, it lies between 30 and 40.

In addition to identified by donor index D of these solvents. Preferably, the donor index of these solvents was between 10 and 30. Specified donor index corresponds to H (enthalpy change), expressed in kilocalories per mole, with the connection specified aprotic polar solvent with pentachloride antimony.

According to the present invention preferably in a polar solvent or solvents that are used in the reagent, no acidic hydrogen. In particular, when the polar nature of the solvent associated with the presence elektronicznych groups, it is desirable that there was no hydrogen in the alpha position in electron functions.

In General, for any of the components used reagents preferably pKa corresponding to the first acidity of the solvent, were equal to at least about 20 (the term "about" means that only the first number is significant, mainly is equal to at least 25, preferably lies between 25 and 35.

The acidic nature can also be expressed through the acceptor indicator And solvent, as defined by Reinhard, "Solvents and Solvent Effects in Organic Chemistry", 2nd edition, VCH (RFA), 1990, pp. 23-24. It is advisable that this acceptor indicator Kislota was at least partially (at least 10 mol%), preferably completely soluble in the environment component of the reagent.

Solvents, gives good results, can be, for example, amide type solvents. These amides include amides with a special character, for example, Tetra-substituted urea, including cyclic Tetra-substituted urea, for example, 5 - or 6-membered, for example, DMRI (dimethylpropanolamine or 1,3-dimethyl-3,4,5,6-tetrahydro-2/1H/pyrimidine) and DMAE (dimethylethanolamine), or 1,3-dimethyl-2-imidazolidinone and monosubstituted the lactam. Preferred amides are substituted (disubstituted for ordinary amides). As an example, pyrrolidone derivatives such as N-organic, or N,N-dimethylformamide, or N,N-dimethylacetamide.

It is also advisable to use a solvent, such as 1,3-dimethyl-3,4,5,6-tetrahydro-2/1H/-pyrimidine (DMRI) or benzonitrile.

Another particularly interesting group of solvents are ethers, which are symmetric or asymmetric, open or not. To the group of ethers should be considered as derivatives of ethers of glycols, such as various slimy, for example, diglyme.

In percarbonic acid, perny effect on dipterology carbon atom, preferably selected from the functional groups, in which the constant Gametepat least equal to 0.1. In addition, preferably, the inductive componentp,iwas at least equal to 0.2, but more preferably of 0.3. In this regard, reference should be made to the work of the March, "Advanced Organic Chemistry", C-nd edition, John Wiley and Son, pp. 242-250, namely, table 4 in this section.

More specifically, the electron-withdrawing group may be selected from halogen atoms, preferably light, for example, chlorine or fluorine. Corresponding percarbonate acid is haloethoxy acid of formula (1):

X - CF2- COOH, where X is a halogen atom, predominantly lung (chlorine or fluorine).

You can also select a group EA of nitrile groups (however, with the possible occurrence of side reactions of alpha-elimination) carbonylic from sulphonated and perftoruglerodnykh groups. In this case percarbonate acid correspond to the formula (2):

R - G - CF2- COOH, where R G is a nitrile group, or G means or/CF2/n- where n is greater than or equal to 1, and R is an inert organic or mineral residue, preferably organic erdy media organic, such as resin or mineral.

If G is performancelevel group/CF2/n- n expediently lies between 1 and 10, preferably between 1 and 5. In this case, the radical R may also be a halogen atom, such as fluorine.

Usually, except when percarbonate acid is a polymer, the total number of carbon atoms in percarbonates acid does not exceed 50.

Protivootecona, capable of forming a salt with the specified percarbonic acid, are mostly large. Thus, the preferred alkali metal salts, mainly those salts, which have an alkaline metal selected from sodium, potassium, rubidium, cesium and France. Preferably, the specified metal refers to the period, the number of which is at least equal to the number of sodium, mainly a series of potassium. Also preferred Quaternary ammonium salt.

You can also improve reaction using cations, or which are surround by nature, for example, cations of Quaternary ammonium or Quaternary of phosphonium, or give them volume by the addition of chelating agents or, preferably, cryptantha, such as, for example, simple is adowanie chelate compounds or chelating agent, it is advisable to choose on the one hand, among the amines and, on the other hand, among ethers, the molecules of which contain at least one other function of simple ether.

Thus, used chelating agents it is advisable to choose such that they contain or at least one amine function; or one function of simple ether and at least one amine function and/or simple ether to obtain complexing agents, preferably bidentate, more preferably tridentate, and features a simple ether and/or amine separated by at least one, mostly two atoms and not more than four, mostly not more than three carbon atoms.

If the atoms for coordination, are connected by two chains that make up the cycle, preferably one chain contains at least 3 flights, mostly 4-level and the other at least 2 mostly 3 link.

The volume and mobility of the molecule must be such that bi-, tri - or polydentate compounds were complexing agents. This does not apply to the case of 1,4-diaza-/2,2,2/-bicyclobutane.

In General, you can specify that you should avoid bicyclic sistolicescoe links not more than 8, especially if the heads of the bridges are atoms, providing coordination, i.e., system type diazabicyclo, heptane and below and to a lesser extent nonane.

More generally, it is advisable to avoid any bicyclic systems:

- who heads the bridges are atoms that are designed to ensure the coordination of communication and

both chains are not given the heads of the bridges have a number of links not more than 2, preferably no more than 3, and if the third circuit has a length of less than 7 units.

At least bidentate nature of the compounds, preferably having at least one aminophenol required for phosgene and its derivatives, but not suitable for oxaliplatin and its equivalents.

The greatest interest represents at least 3 classes of complexing agents: including oxygen-containing tertiary amines; oxygen - or sulfur-containing cyclic or macrocyclic ethers and cryptand.

The first class consists of chelating agents of General formula:

N-[CHR1-CHR2-O-/CHR3-CHR4/n-R5]3, (1)

in which n is an integer bolshushiye, represent a hydrogen atom or an alkyl radical containing 1-4 carbon atoms, a R5is an alkyl radical or cycloalkyl radical having 1-12 carbon atoms, phenyl radical or a radical of the formula-CmH2mC6H5ormH2m+1-C6H5lies between 1 and about 12.

The second class of complexing agents consists of cyclic polyethers, preferably macrocyclic having from 6 to 30 atoms in the cycle, preferably from 15 to 30 atoms in the cycle, and comprising from 2-10, preferably 4-10 parts-O-X, in which X is or-CHR6-CHR7- or-CHR6-CHR8-CR9R7where R6, R7, R8and R9identical or different, are hydrogen atom or alkyl radical having 1-4 carbon atoms, one of X can be-CHR6-CHR8-C R9R7if fragments-O-X - containing group,- O-CHR6-CHR7.

The third class of complexing agents consists of the compounds described in European patent application EP 0423008, page 3, line 29 to page 6, line 45.

It is advisable to use such salts perfluoroine carbonic acid, as triptoreline complexing agents of the type of simple crown ethers in solvents, which are relatively polar (less polar than DMF), significantly accelerates the transformation of the original percarbonic acid.

These complexing agents can be preferably used from the calculation of 5-100% mole., for example 5-25% mole. from the initial content percarbonic acid.

However, in certain combinations with other components of the reaction medium, for example, some solvents, may be less favorable effect, for example, in relation to the stability of the final product, and, therefore, such combinations are not considered as appropriate.

Another object of the present invention is to develop a method of producing an organic derivative containing deformationof group, which uses the reagent according to the invention.

According to this method:

a) a reagent is introduced into contact with a compound containing at least one electrophilic function, and

b) heat the mixture at a temperature between 100 and 200oWith, preferably between 110 and 150oWith, for at least half an hour, mostly at least one hour and not more than a day, mostly less than 20 to be at a temperature, favorable for the introduction of another. This introduction may be gradual. You can pour the reagent into the substrate or Vice versa. You can enter percarboxylic and the substrate simultaneously and gradually in the solvent.

The reagent according to the invention reacts with the electrophilic compound containing an electrophilic atom, this atom may be a carbon atom or a heteroatom, for example, sulfur atom, selenium or tellurium. Mainly, it reacts with the hydrocarbon compounds according to the electrophilic carbon atom that is not part of an aromatic system.

According to the first aspect of the invention, the reagent reacts preferably with compounds containing an electrophilic atom, mainly electrophilic heteroatom connected with a halogen atom or pseudohalogen the group for the replacement of the specified halogen or pseudohalide at one stage.

The reaction takes place the better, as opposed to SN2, when passing through the formation of intermediate reaction product originating from the joining of multiple or double bond.

When the electrophilic atom is a sulfur atom, the reaction can be carried out with:

halide what theilgaard, where a halogen atom or pseudohalogen group is replaced during the reaction of substituted deformational group;

- disulfides, for example, arylsulfatase, possibly substituted, where S-S-link is broken and replaced by substituted deformational group; the corresponding disulfides can be, for example, ridiculed C5-C10possibly substituted C1-C10is an alkyl group, a C1-C10-alkoxygroup, the nitro-group or one or more (3) halogen atoms;

connections type thiocyanate, where the cyano is substituted during the reaction of substituted deformational group; preferred thiocyanates are5-C10-aristocraty, including alkylarylsulfonate, and C1-C10-allcitizens, including analcitizen.

In the above compounds, the halogen atom may be selected from among the atoms of iodine, bromine, chlorine and fluorine. Group "pseudohalide" is a group which is removed in anionic form and represents an acid, pKa below 4, preferably below 3, in particular below 10.

Prefer group associated acid which has an acidity as measured by the constant Hammerdrilling acids. One of the typical pseudohalide is performancecountercategory that releases performancereport. Preferred pseudohalide group can be selected among tosylate (p-toluensulfonate), mesylates (methylsulfonylamino), tripterocalyx or triptracker. You can also consider an acetate group as such the deleted group.

According to the second aspect, the reagent mostly also comes in a reaction with a compound selected among the carbonyl compounds like ketones, aldehydes, golodnikov acids or activated esters, anhydrides, acids, this accession shall be effected by a carbonyl function. As a preferred and non-limiting examples of aromatic aldehydes, preferably C5-C10in which the aromatic nucleus may be substituted WITH1-C10is an alkyl group, a C1-C10-alkoxygroup, the nitro-group or a halogen atom; cyclic ketones, such as cyclohexanone; neoliberalist activated donor group of the ketones, for example, triptoreline; aromatic anhydrides, for example, benzoic anhydride.

In this case, the reaction product is typically an alcohol (e.g., in the form of an alcoholate), in which the carbon atom bearing the hydroxyl function is replaced substituted deformational group. This product can then interact with the reagent or with the original product, depending on the reaction conditions.

Generally, the amount of reagent introduced into the process of the invention is defined by the known method in accordance with the functionality of electrophilic compounds.

It should be noted that the product obtained by the decomposition percarbonic acid, can interact with itself, if it contains one of the functions that are able to interact, such as mentioned above.

It should be noted that compounds with electrophilic function, which is in liquid form, can be used as a solvent according to the present invention in the case when they are aprotic. It is also advisable to carry out the reaction of the present invention in the presence of:

a) salt percarbonate acid such as defined above, and

b) compounds containing at least one electrophilic function, acting both as solvent is terrasim at least one electrophilic function it is important that this last little as possible broke the previously described conditions.

Thus, it is preferable to use relatively dehydrated substrate, or do not contain acidic hydrogen, open strong bases or harmful impurities, i.e., in General, one that meets the same requirements that apply to the reagent.

You can set that under all conditions being equal, the yield of the desired organic derivative depends on the degree of reaction and that you can get a very low end output, despite the substantial conversion of the reactants. Without resorting to any scientific theory, it is assumed that there kinetics of the formation and decomposition kinetics of the products obtained.

To avoid a very large degradation of the final product and therefore provide good selectivity of the reaction, it is preferable not to achieve complete conversion of the original percarbonic acid. The reaction can be controlled by the degree of transformation (TT) acid, which is a molar ratio of the amount of spent acid to the number of initial acid in the reaction mixture, and the degree of mouthbrooding reaction only to the degree of transformation of 40-80%, preferably 50-70%, then separate the reaction products. Thus it is possible to achieve a selectivity of about 80%, expressed as the molar ratio of the target product to developed percarbonic acid.

In order to be in optimal reaction conditions, it is possible to limit the degree of transformation, acting simultaneously on the duration of the reaction, the solvent nature and the presence of auxiliary substances, which tend to restrict this transformation, such as, for example, fluoride ions. In addition, the kinetics of the reaction depends on the reaction of components (percarbonate acid and electrophilic reagent) and the corresponding reaction time is easy to change from case to case depending on this kinetics.

Upon reaching the desired degree of conversion of the reaction mixture can be processed in a known manner to separate the resulting product, with the original products can be recicladora for more number of target organic derivative.

In some cases, separation, you can use additional chemical reaction that turns the target product in a more volatile and easily Athanasius connection.


< / BR>
In nitrogen atmosphere mixing 26 g of anhydrous DMF, to 4.98 g (32.7 mmole) of triptoreline and K 2 g (18,8 mmole) of benzaldehyde.

The molar ratio of triptoreline to benzaldehyde is 1.7.

The resulting mixture was transferred into a reactor of steel grade of Hastle capacity of 50 ml and Then the reactor was sealed, the mixture is heated at 104oWith over 3.5 hours

After cooling to 5oWith crude decant the reagent, diluted with CH2CL2and washed with water.

The organic phase is dried, then analyzed by chromatography in the gaseous phase.

The degree of transformation (TT) benzaldehyde is 50% (the number of moles converted benzaldehyde in relation to the number of moles of the original benzaldehyde) and real output (RR) is 20% 1-triftormetilfosfinov alcohol.

Example 2

The reaction between trifurcation potassium and benzaldehyde carried out according to the method of example 1, substituting DMF for N (N-organic.

Dissolve 7.6 g CF3CO2-K+(50 mmol) and 3.2 g of benzaldehyde (30 mmol) in 40 g N.

The water content in the environment below 4 mol.% in relation to triptoreline.

The mixture is heated at 140oWith over 3.5 hours

Processing the benzaldehyde is 55%.

Output 1-triftormetilfosfinov alcohol is 15%.

Example 3

The reaction between trifurcation potassium and benzaldehyde carried out according to the method of example 1, replacing DMF) in acetonitrile. Dissolve 2 g of benzaldehyde and of 4.75 g of triptoreline potassium in 25 ml of CH3SP.

The mixture is heated at 140oWith over 3.5 hours

After processing and analysis of the crude reaction product get:

the degree of conversion of benzaldehyde = 53%,

output 1-triftormetilfosfinov alcohol = 2,5%.

The main product formed in this reaction is cinnamonitrile (isomers Z and E).

Cinnamonitrile is formed by condensation of the anion of acetonitrile with benzaldehyde and subsequent dehydration.

This example shows that the solvent used should not be too acidic protons.

Example 4

In the conditions of example 1 carried out the reaction between trifurcation potassium (of 5.05 g, 32.7 mmole) and para-vorbesuregen (2.5 g, at 20.2 mmole) in 25 ml DMF.

The mixture is heated at 140oC for 4 h

After processing and analyzing chromatographia in the gas phase (GFH) get:

TT p-forventelige = 75%,

RR 1-trifluoromethyl-/p-forbesi formethylcarbamoyl to pair-fermentology:

< / BR>
This reaction shows that the use of the electrophile with multiple reactive functions may develop adverse reactions.

Example 5

A mixture of 1.43 g CF3CO2-K+(9,44 mmole) and 0.55 g of cyclohexanone (5.6 mmole) diluted 6.4 g of DMF is heated at 140oWith over 5,5 hours Analysis using GFH crude reaction product after hydrolysis gives:

< / BR>
or

< / BR>
The main resulting products are condensation products of cyclohexanone with yourself, with subsequent dehydration:

< / BR>
This reaction shows that, when the electrophile has analiziruyutsya function, can have adverse reactions.

Example 6

The reaction triftoratsetofenona with CF3CO2-K+< / BR>
A mixture of 0.87 g (5.7 mmole) CF3CO2-TO+and 0.62 g (of 3.56 mmole) of triftoratsetofenona dissolved 6.5 g of DMF is heated at 140oWith over 5,5 hours

After cooling and hydrolysis analysis using GFH gives:

< / BR>
< / BR>
This reaction can be conducted in N instead of DMF.

Example 7

The reaction between benzoic anhydride and trifurcation potassium

The mixture 0,81 g (5,32 Iim for 5.5 hours After hydrolysis analysis GVH reaction medium gives:

TT //FSO/2/ = 100%

< / BR>
< / BR>
< / BR>
Bis-triftormetilfosfinov is formed by cryptomelane of triftoratsetofenona formed as an intermediate product:

< / BR>
N, N-dimethylbenzamide get the reaction of decomposition of DMF, which leads to N,N-dimethylamine, which in turn reacts with benzoic anhydride:

< / BR>
The reaction between benzoic anhydride and CF3CO2-K+also can be carried out in DMF.

Example 8

The reaction between diphenylsulfide C6H5SSC6H5and CF3CO2-K+< / BR>
A mixture of 0.83 g (5,46 mmole) CF3CO2-TO+, 0.6 g (to 2.75 mmole) of diphenyldisulfide in 6.2 g of DMF is heated at 140oC for 6 h

Analysis of the reaction medium (after hydrolysis) using GFH and 19F-NMR spectrum gives:

TT /S6H5SECURITY STANDARDS6H5/ = 67%,

RR /C6H5SF3/ = 84%.

The reaction can also be carried out in N.

Counter-example

Work according to the method of example 8, but with the added addition of si I - 20% mole. in relation to the original CF3WITH-2TO+(5,46 mmole),Ktsia between di-/4-nitrophenyl/-disulfide and CF3CO2-TO+< / BR>
Work according to the method of example 8 with a mixture of 0.82 g (5,39 mmole) CF3CO2-TO+, 0,83 g (2.7 mmole) of di-/4-nitrophenyl)-disulfide in 7 g of DMF, get a crude reaction product containing in addition to the original di-/4-nitrophenyl)-disulfide 4-nitrotetrazolato

< / BR>
Example 10

The reaction benzylcyanide C6H5CH2SCN c CF3CO2-K+< / BR>
A mixture of 0.67 g (of 4.45 mmole) CF3CO2-K+, 0,42 g (2.8 mmole) benzylcyanide 5 g of DMF is heated at 140oC for 3 h

After hydrolysis analysis GFH crude reaction product gives:

TT /S6H5-CH2SN/ = 100%

RR /S6H5-CH2SCF3/ = 36%.

The reaction can be conducted in N this way.

1. The reagent for introducing a substituted deformational group, in particular triptoreline, electrophilic compound containing an electrophilic atom selected from atoms of carbon, sulfur, selenium or tellurium, characterized in that it contains a) percarbonate acid of the formula EA - CF2- COOH, where EA represents an electron-withdrawing atom or group selected from the electrophilic groupl with mineral or organic cation, b) an aprotic polar solvent, and the molar content of the released protons, which are these different components, including impurities is not more than half of the original molar concentration percarbonic acid.

2. The reagent under item 1, characterized in that percarbonate acid is an acid corresponding to the formula EA - CF2- COOH, where EA denotes a halogen atom or a group R-G R-G means a nitrile group; or G represents or and R is an organic radical selected from aryl, alkyl or aralkyl, possibly substituted; or G represents -(CF2)n- where n has a value from 1 to 10, and R represents a halogen atom.

3. The reagent under item 1 or 2, characterized in that it includes a) percarbonate acid of the formula EA - CF2- COOH, where EA represents a halogen atom or a group R-G R-G represents a nitrile group, or G is or and R is an organic radical selected from aryl, alkyl or aralkyl, possibly substituted; or G means - (CF2)n- where n has a value from 1 to 10 and R denotes a halogen atom, and percarbonate acid is converted into a salt with POM what about ammonium, and b) the polar aprotic solvent, and the molar content of the released protons, which are these different components, including impurities is not more than half of the original molar concentration percarbonic acid.

4. The reagent under item 1, characterized in that it includes a) percarbonate acid of the formula EA - CF2- COOH, where EA represents a halogen atom or a group R-G R-G represents a nitrile group, or G is or and R is an organic radical selected from aryl, alkyl or aralkyl, possibly substituted; or G means -(CF2)n- where n has a value from 1 to 10 and R denotes a halogen atom, and percarbonate acid is converted into a salt with the cation of an alkali metal selected from sodium, potassium, rubidium, cesium, or France, or salt of Quaternary ammonium, and b) an aprotic polar solvent, whose relative dielectric constant is at least equal to 5, and the molar content of the released protons, which are these different components, including impurities is not more than half of the original molar concentration percarbonic acid.

5. The reagent under item 1, Otley halogen atom or a group R-G, where R-G means a nitrile group; or G means or and R is an organic radical selected from aryl, alkyl or aralkyl, possibly substituted, or G means -(CF2)n- where n has a value from 1 to 10 and R denotes a halogen atom, and percarbonate acid is converted into a salt with the cation of an alkali metal selected from sodium, potassium, rubidium, cesium, or France, or the Quaternary ammonium salt; and b) an aprotic polar solvent selected from amides, including Tetra-substituted urea and monosubstituted the lactam, 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)pyrimidinone (DMPU), 1,3-dimethyl-2-imidazolidinone (DMI or DMEU), benzonitrile and symmetrical or unsymmetrical ethers, including ethers, glycols, and the molar content of the released protons, which are these various components, including impurities, is the largest half of the original molar concentration percarbonic acid.

6. The reagent in one of the paragraphs. 1-5, characterized in that the molar concentration of protons is the largest 10% of the molar concentration percarbonic acid.

7. The reagent in one of the paragraphs. 1-5, characterized in that the molar content of water , trichosis the fact that the molar ratio of the transition metal element having at least two valence States, for percarbonates acid below 1: 1000.

9. The reagent in one of the paragraphs. 1-8, characterized in that the molar ratio of the transition metal of group VIII of the periodic system of elements to percarbonates acid is less than 1: 10000.

10. The reagent in one of the paragraphs. 1-9, characterized in that the molar ratio of fluoride ion, expressed in equivalent to percarbonic acid, less than or equal to 1: 1.

11. The reagent in one of the paragraphs. 1-10, characterized in that the donor coefficient polar aprotic solvent, which characterizes the ability to solutionat cations ranges from 10 to 30.

12. The reagent in one of the paragraphs. 1-11, characterized in that the acceptor ratio of solvent equal to less than 20.

13. The reagent in one of the paragraphs. 1-12, characterized in that the pKa value corresponding to the initial acidity of the solvent is at least equal to 20.

14. The reagent in one of the paragraphs. 1-13, characterized in that it contains a complexing crown-ether.

15. The reagent in one of the paragraphs. 1-14, characterized in that the salt percarbonate acid completely rastgoo least one electrophilic function performs the function of an aprotic solvent and represents a carbonyl compound.

17. The reagent under item 1, characterized in that it contains triptorelin potassium as salt percarbonate acid.

18. The reagent under item 17, characterized in that completely soluble in the reaction medium.

19. The reagent in one of the paragraphs. 1-18, characterized in that the salt is a potassium salt.

20. The reagent in one of the paragraphs. 1-19, characterized in that the solvent is selected from N-disubstituted amides and acetonitrile.

21. How peralkaline, in particular, perftoruglerodnye electrophilic compounds containing an atom selected from carbon, sulfur, selenium or tellurium, by nucleophilic substitution or accession, wherein the electrophilic compound is introduced into contact with the reagent in one of the paragraphs. 1-20, the resulting mixture is heated at a temperature of 100-200oC for from 1/2 hour before day until the degree of conversion of the parent compound, comprising 40-80% and allocate the resulting product.

22. The method according to p. 21, wherein the electrophilic compound does not contain hydrogen, tsepliaeva strong base.

23. The method according to pawley a carbonyl compound.

Priority points and features:

24.03.1995 on PP. 1-23;

29.12.1995 under item 1 is the molar content of the released protons, which are these different components, including impurities is not more than half of the original molar concentration percarbonates acid; PP. 12 and 14.

 

Same patents:

The invention relates to the synthesis of organic compounds, specifically to methods of producing trifluoromethyl-3,4-dichlorobenzene

The invention relates to a method for producing fluorine-containing compounds by reacting aromatic compounds not containing in the core heteroatoms or containing in the core up to three nitrogen atoms, substituted in the nucleus exchanging atoms and fluorine atoms, chlorine or bromine, and containing optionally at least one additional Deputy promoting nucleophilic substitution of aromatic compounds with fluoride or a mixture of fluorides of the General formula I MeF, where Me denotes the cation of the alkaline earth metal, ammonium ion or alkali metal ion, in the presence of a solvent or without it at a temperature of from 40 to 260oWith

The invention relates to a new process for the preparation of 2,4,6-tribromophenol, used in the synthesis of the drug Kseroforma", applied topically as an astringent, drying and antiseptic agent in powders, powders, ointments (3-10%) (Mashkovsky M. D.

The invention relates to a carbon electrode used as anodes in electrolytic cells for obtaining fluorine by electrolysis of molten electrolyte of potassium fluoride and hydrogen fluoride, as well as to the electrolyzer for receiving fluoride and operation method of electrolysis to obtain fluorine and reactor for fluorination

The invention relates to the field of chemistry of organic compounds, specifically to methods for producing carboxylic acid anhydrides of the following structure:

< / BR>
These compounds are widely used as intermediates in organic synthesis

The invention relates to the synthesis of organic substances, in particular 2-chloro-4-NITROPHENOL, which is used as the beginning of the current antifungal drug "Nitrofungin"

The invention relates to an improved method for producing 2,2-bis-(3,5-dibromo-4-hydroxyphenyl) propane (tetrabromdifenilolpropan, tetrabromobisphenol, TRIP), which can be used as a flame retardant to obtain epoxy resins with low Flammability, used in electrical products with improved dielectric properties and other polymeric materials

FIELD: organic chemistry.

SUBSTANCE: invention relates to method for production of fluorinated ketone of general formula 5 . Claimed method includes reaction of compound of formula 3 , containing at least 30 wt.% of fluorine with fluorine in liquid phase, containing solvent selected from group comprising perfluoroalkane, perfluorinated ester, perfluorinated polyether, chlorofuorohydrocarbon, chlorofluoropolyether, perfluoroalkylamine, inert liquid, compound of formula 2 , compound of formula 6 to produce compound of formula 4 , followed by dissociation of ester bond in formula 4 in presence of KF, NaF or activated carbon without solvent. In formulae: RA represents, optionally containing ether-forming oxygen atom, wherein each of said groups contains C1-C10 carbon atoms; RAF represents C1-C10-perfluorenated RA group; RB represents alkyl optionally containing ether-forming oxygen atom, partially halogenated alkyl, optionally containing ether-forming oxygen atom, wherein each of said groups contains C1-C10 carbon atoms; RBF represents C1-C10-perfluorenated RB group; RC and RCF groups are identical ones and each RC and RCF contains C2-C10 carbon atoms and represents perfluorenated alkyl optionally containing ether-forming oxygen atom, partially halogenated alkyl, optionally containing ether-forming oxygen atom or RA and RB together form alkylene group optionally containing ether-forming oxygen atom, partially halogenated alkylene, optionally containing ether-forming oxygen atom, wherein each abovementioned group contains C3-C6 carbon atoms; each RAF and RBF are perflurenated RA and RB groups containing C3-C6 carbon atoms; groups are identical ones and each RC and RCF contains C2-C10 carbon atoms and represents perfluorenated alkyl optionally containing ether-forming oxygen atom, partially halogenated alkyl, optionally containing ether-forming oxygen atom. Method of present invention provides fluorinated ketone production with 71-96 % yield. Some intermediates of formula 3 also are described.

EFFECT: method for fluorinated ketone production with increased yield.

10 cl, 5 ex

FIELD: chemical industry; method of production of the fluorine-containing compounds.

SUBSTANCE: the invention is pertaining to the chemical industry, in particular, to the improved method of production of fluorine-containing compounds from the halogen-containing, compounds, preferably, from chlorine-containing compounds due to an exchange of halogen for fluorine at presence of the HF-additional compound of the mono- or bicyclic amine with at least two atoms of nitrogen. At that at least one atom of nitrogen is built in the cyclic system as the fluorating agent; or at presence of anhydrous hydrogen fluoride - as the fluorating agent and the indicated HF-additional compound of the mono- or bicyclic amine as the catalyst. At usage of the applicable solvents the reaction mixtures can be divided into two phases and thus to simplify the reprocessing of the products. The invention also is pertaining to the HF-additional compounds of 1.5-diazabicyclo[4.3.0]non-5-en and N,N-dialkylaminopiridin, where alkyl represents C1-C4alkyl and where the molar ratio of HF to amine makes 1:1, and to HF- additional compounds 1.8- diazabicyclo[5.4.0]undecyl-7-ene, where the molar ratio of HF to amine compounds more than 1:1.

EFFECT: the invention ensures at usage of the applicable solvents to divide the reaction mixture into two phases and thus to simplify reprocessing of the products.

17 cl, 13 ex

FIELD: chemistry.

SUBSTANCE: reagent can additionally contain an acid. The iron compound can be iron (II) sulphate, iron (II) ammonium sulphate, iron (II) tetrafluoroborate, ferrocene, bis(η5-pentamethylcyclopentadienyl)iron or iron powder. The sulphoxide can be dimethylsulphoxide. The peroxide can be hydrogen peroxide or a hydrogen peroxide-urea complex. The acid can be sulphuric acid, tetraboric acid or trifluoromethane sulphonic acid.

EFFECT: high degree of general versatility and high efficiency.

13 cl, 17 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing 3,5-disubstituted-2,4,6-triiodophenols of formula (2) (where values of radicals R and R' are defined in claim 1). The method is realised via electrochemical generation of I+ cations from a natural iodine source in the presence of a protonic polar in a separate reactor. 3,5-disubstituted phenols are then iodised in the presence of I+ cations obtained at the previous step. The invention also relates to methods of producing compounds of formula (5) iopamidol and iomeprol.

EFFECT: improved methods.

15 cl, 8 ex

FIELD: chemistry.

SUBSTANCE: reagent can additionally contain an acid. The iron compound can be iron (II) sulphate, iron (II) ammonium sulphate, iron (II) tetrafluoroborate, ferrocene, bis(η5-pentamethylcyclopentadienyl)iron or iron powder. The sulphoxide can be dimethylsulphoxide. The peroxide can be hydrogen peroxide or a hydrogen peroxide-urea complex. The acid can be sulphuric acid, tetraboric acid or trifluoromethane sulphonic acid.

EFFECT: high degree of general versatility and high efficiency.

13 cl, 17 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to preparing alkylbenzyldimethylammoniumfluorides possessing antiviral and antibacterial action. The declared method consists in a reaction of a mixture of 1.5 M alkyl iodide of formula RJ, wherein R represents alkyl C8H17-C18H37, in absolute alcohol with dimethylbenzylamine at boiling; that is followed by a sequential ethanol stripping in vacuum, resolution of a residue in ethyl acetate, drying in diethyl ester, separation of an oil-precipitated intermediate product and residual ester stripping. The intermediate product is resolved in mixed ethanol and water in volume ratio 1:1 and titred in 10% aqueous AgF until iodide ions disappear from the solution; the solution is filtered, and the filter is boiled down, and crystallised from mixed methanol and hexane.

EFFECT: method provides preparing effective low-toxic therapeutic agent.

2 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to the improved method for preparing 1,3-dichloropropanol-2 (α-dichlorohydrin-glycerol) used in producing glycerol fats, plastic masses and putties. Method involves hydrochlorination reaction of epichlorohydrin with gaseous hydrogen chloride carried out in reactor at temperature 20-25°C and this hydrochlorination reaction is carried out in the presence of saturated calcium chloride solution in water in the amount from 0.03% to 0.04% (by mass) of epichlorohydrin mass, volume rate feeding hydrogen chloride from 900 h-1 to 1000 h-1 and the equimole ratio of epichlorohydrin to hydrogen chloride. Method provides 99.4% yield of 1,3-dichloropropanol-2, to simplify technology due to the complete conversion of parent reagents and to exclude the recirculation stage of hydrogen chloride.

EFFECT: improved preparing method.

1 tbl, 4 ex

FIELD: industrial organic synthesis.

SUBSTANCE: invention relates to production of α,ω-chloroalkanes (chlorohydrins), which are employed for production of diol monoethers used in varnish-and-paint industry in production of polyoxyamides, such as Niplon-2 varnish, designed for impregnation of glass-carbon fabrics to impart heat-retention properties as well as intermediates in production of dyes, halogen-substituted polymers, pharmaceutics, polymerization catalysts, plasticizers. Process of invention comprises catalytic chlorination of diols with carbon tetrachloride in presence of 0.1 mmole Mo(CO)6 at 120-140°C for 3-8 h, wherein molar ratio Mo(CO)6/diol/CCl4 = 1:200:1000.

EFFECT: reduced consumption of catalyst and reaction time, increased selectivity, reduced expenses, and simplified technology.

1 tbl, 2 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to the method of producing dichloropropanols 1,3-dichloro-2-propanol and 2,3-dichloro-1-propanol through hydrochlorination of glycerine and/or monochloropropanediols by gaseous hydrogen chloride with carboxylic acid catalysis. Hydrochlorination is carried out at least in a single continuous reaction zone at reaction temperature 70-140°C and continuous removal of reaction water by distillation at low pressure. The liquid raw material contains at least 50 wt % glycerine and/or monochloropropanediols. The invention also pertains to versions of the apparatus for realising the method of producing dichloropropanols.

EFFECT: target products with high output and high selectivity of the reaction system.

16 cl, 4 tbl, 4 ex

FIELD: chemistry.

SUBSTANCE: proposed method involves reacting glycerine with hydrogen chloride gas at high temperature in the presence of carboxylic acids and their derivatives. The process is carried out in the presence of organic and/or inorganic heterogeneous acid type catalysts. As a rule, the inorganic heterogeneous catalysts used are silica gel, aluminium silicate, aluminium oxide and activated carbon, and the organic heterogeneous catalysts used are ion-exchange polymer materials, containing acid groups. The process is usually carried out at 100-140°C.

EFFECT: higher degree of converting glycerine and hydrogen chloride, and output of dichloropropanols.

5 cl, 1 tbl, 6 ex

FIELD: chemistry.

SUBSTANCE: method involves dichlorinating glycerol with gaseous hydrogen chloride at temperature of 70-140°C in the presence of a carboxylic acid and a water-insoluble organic solvent, wherein the process is carried out in a combined reaction/rectification reactor, and the organic solvent is selected such that it forms an azeotrope with water but not with glycerol dichlorohydrins.

EFFECT: method reduces contact time and increases output of glycerol dichlorohydrins.

3 cl, 1 tbl, 7 ex

FIELD: chemistry.

SUBSTANCE: pentaerythrite is subjected to interaction with chloranhydrides of organic acids C2-C5 of normal and iso-structure. Reaction is realised at temperature 150-200°C, preferably 170-190°C, in closed reactor with obtaining monoether of pentaerythrite trichlorohydrin with the following removal of carboxyl group by alkaline or acid hydrolysis or transesterification with alcohols C1÷C3 in presence of catalysts - acids of Lewis and(or) Brensted. Obtained pentaerythrite trichlorohydrin is clarified by vacuum distillation.

EFFECT: method makes it possible to simplify the process and simultaneously increase its selectivity.

1 tbl, 12 ex

Up!