KR20100050524A - Process for the synthesis of diaminopyridine and related compounds - Google Patents
Process for the synthesis of diaminopyridine and related compounds Download PDFInfo
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C07D213/73—Unsubstituted amino or imino radicals
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Abstract
Methods of synthesizing diaminopyridine, for example 2,6-diaminopyridine and related compounds, are used industrially as compounds and as components in the synthesis of various useful materials. The synthesis proceeds by chlorine-ammonia substitution in the presence of a copper source.
Description
This application claims the benefit of US Provisional Patent Application No. 60 / 953,259, filed August 1, 2007, which is incorporated by reference in its entirety for all purposes.
The present invention relates to the preparation of diaminopyridine, for example 2,6-diaminopyridine and related compounds, used industrially as precursors and intermediates in the synthesis of various useful materials.
Compound 2,6-diaminopyridine:
Silver dyes, metal ligands, pharmaceuticals, pesticides, and monomers for incorporation into polymers are commonly used as starting materials for the preparation of various products, including those disclosed in US Pat. No. 5,674,969.
It is known to produce diaminopyridine by a Chichibabin amination reaction in which pyrimidine reacts with sodium amide in an organic solvent. This is a complex reaction that requires relatively harsh conditions (eg, a temperature of 200 ° C. at high pressure). In addition, the reaction is uneconomical because relatively expensive sodium amides have to be used in excess to prevent dimerization, and the process complexity associated with separation, handling of harmful sodium amides and waste disposal increases manufacturing costs.
Another method for preparing diaminopyridine is a three step modification of epichlorohydrin. This method is generally low in productivity and requires the use of excess sodium cyanide and handling of HCN. In addition, purification of the intermediate hydroxyglutaronitrile is required to achieve acceptable yields of the DAP product.
It is known to substitute chlorine from dichloropyridine with ammonia or amines. One method is the preparation of aminopyridine from chloropyridine and ammonia, for example in the presence of a copper sulfate catalyst, which is described in Rec. Trav. Chim., 58, 709-721 (1939) and German Patent No. 510,432. However, yields in this method are typically too low for commercial survival.
In Japanese Patent No. 53 / 053,662, aminopyridine is prepared by treating chloropyridine containing at least one chlorine atom in the 2- or 6-position of a pyridine nucleus with aqueous NH 3 in the presence of metal Cu or Al. The relatively large amounts of copper or aluminum powder, and relatively high temperatures and pressures necessary to carry out this reaction, make the reaction undesirably difficult, and again, the yield of 2,6-diaminopyridine is generally not viable for commercial survival. Too low
Thus, there remains a need for low temperature, low pressure, high selectivity methods for the preparation of diaminopyridine, for example 2,6-diaminopyridine and related compounds.
In one embodiment, Formula I:
[Formula I]
A method for synthesizing a compound represented by the structure of is described herein, the process comprising (a) the following formula II:
[Formula II]
Contacting the compound represented by the structure of with a copper source in an aqueous ammonia solution to form a reaction mixture, wherein the aqueous ammonia solution is buffered to a pH of about 4 to about 8; (b) heating the reaction mixture; In formula (I) and formula (II), R 1 and R 2 are each independently selected from the group consisting of:
(a) H;
(b) alkyl, aryl or aralkyl radicals;
(c) NR 3 R 4 , wherein R 3 and R 4 are each independently
(i) H,
(ii) alkyl, aryl or aralkyl radicals,
(iii)
(iv) —C (O) —NR 5 R 5 , wherein each R 5 is as defined above; or
(d) OR 6 where R 6 is
(i) H,
(ii) an alkyl, aryl or aralkyl radical, or
(iii)
In another embodiment, there is provided a process for preparing an oligomer or polymer by conversion of a compound represented by the structure of formula (I) prepared by the process to an oligomer or polymer.
In another embodiment, there is provided a compound of formula (I) obtained or obtainable by the above process.
In the methods described herein, the synthesis of diaminopyridine ("DAP"), such as one of the various compounds represented by the structure of Formula (I), proceeds by chlorine-ammonia substitution in the presence of a copper source.
In one embodiment, Formula (I):
[Formula I]
A method for synthesizing a compound represented by the structure of is described herein, the process comprising (a) the following formula II:
[Formula II]
Contacting the compound represented by the structure of with a copper source in an aqueous ammonia solution to form a reaction mixture, wherein the aqueous ammonia solution is buffered to a pH of about 4 to about 8; And (b) heating the reaction mixture; Wherein in formula (I) and formula (II), R 1 and R 2 are each independently selected from the group consisting of:
(a) H;
(b) alkyl, aryl or aralkyl radicals;
(c) NR 3 R 4 , wherein R 3 and R 4 are each independently
(i) H,
(ii) alkyl, aryl or aralkyl radicals,
(iii)
(iv) —C (O) —NR 5 R 5 , wherein each R 5 is as defined above; or
(d) OR 6 where R 6 is
(i) H,
(ii) an alkyl, aryl or aralkyl radical, or
(iii)
As used herein, the term "alkyl" denotes a monovalent group derived by removing a hydrogen atom from any carbon atom from an alkane: -C n H 2n +1 where n = 1. Alkyl radicals may be C 1 to C 20 straight chain, branched or cycloalkyl radicals. Examples of suitable alkyl radicals include the methyl, ethyl, n-propyl, i-propyl, n-butyl, t-butyl, n-pentyl, n-hexyl, cyclohexyl, n-octyl, trimethylpentyl, and cyclooctyl radicals. Include.
As used herein, the term "aryl" refers to a monovalent group where the free valence is relative to the carbon atom of the aromatic ring. The aryl moiety may comprise one or more aromatic rings and may be substituted with inert groups, ie groups whose presence does not interfere with the reaction. Examples of suitable aryl groups include phenyl, methylphenyl, ethylphenyl, n-propylphenyl, n-butylphenyl, t-butylphenyl, biphenyl, naphthyl and ethylnaphthyl radicals.
As used herein, the term "aralkyl" refers to an alkyl group having an aryl group. Examples of suitable aralkyl radicals include benzyl (ie, C 6 H 5 CH 2 -radicals) and phenylethyl (ie, phenethyl, C 6 H 5 CH 2 CH 2 -radicals).
In one embodiment of the methods described herein, the compound represented by the structure of formula (I) is an aqueous buffered compound represented by the structure of formula (II) (hereinafter referred to as "chloroamino pyridine" or "CAP"). Prepared by contacting a copper source in ammonia solution to form a reaction mixture and heating the reaction mixture. In certain embodiments of formula II, R 1 and R 2 can each be H. When R 1 and R 2 are each H, the compound represented by the structure of formula II is 2-amino-6-chloropyridine, and the compound represented by the structure of formula I prepared by this method is 2,6 -Diaminopyridine. Such a reaction is outlined below:
The compound represented by the structure of formula (II) is, for example, an amide of 2-chloropyridine as disclosed in Japanese Patent No. 59 / 053,910 (Koei Chemical Co., Ltd.). Aging; Reaction of 3-hydroxyglutaronitrile with anhydrous HCl [Ferrarini et al, Journal of Heterocyclic Chemistry, 18, (1007-1010 (1981)); or hydrolysis of 2-acetamido-6-chloropyridine by sulfuric acid (In the same document as above) CAPs are also commercially available, for example, from Sigma-Aldrich (St. Louis, MO).
The copper source may be elemental copper [Cu (0)], or a copper compound such as a Cu (I) compound or a Cu (II) compound such as a Cu (I) salt or a Cu (II) salt, or a mixture thereof have. Examples of copper compounds suitable for use in the present invention include, without limitation, CuCl, CuBr, CuI, Cu 2 SO 4 , CuNO 3 , CuCl 2 , CuBr 2 , CuI 2 , CuSO 4 , and Cu (NO 3 ) 2 . . CuBr and CuI are particularly preferred. The copper source is believed to act as a catalyst in the reaction. While acting as a catalyst, the copper source will not participate in the reaction in any way that will be chemically altered, but nevertheless is believed to alter one or more parameters of the reaction, thereby enhancing product formation. As a result, the copper source is provided to the reaction mixture in a catalytically effective amount, i.e. in an amount capable of achieving such an object.
The amount of copper used in the reaction is typically from about 0.5 to about 7 mole percent, based on the number of moles of the compound of formula II present in the reaction mixture. Ammonia concentrations typically range from about 5 to about 10 moles per mole of compound of formula II present in the reaction mixture.
The aqueous ammonia solution can be buffered by adding a buffer to it. Buffers are substances that do not directly participate in the reaction but, by their presence, limit the pH of the reaction mixture to preselected limits. Frequently, a buffer is a substance that is a weak acid / pair base pair, or a weak base / pair acid pair, with respect to the Bronsted-Rouri acid. The buffer will limit the pH change of the reaction mixture to a preselected range with respect to events such as addition of acid or alkali to the system, or dilution of the reaction mixture, in equilibrium by gain or loss of protons. . The addition of a buffer to the reaction mixture of the present invention results in a buffered solution, wherein the pH in the solution is at least about 4.0, at least about 4.5, at least about 5.0, or at least about 5.5, and at most about 8.0, at most about 7.5, Or less, or less than or equal to about 6.5. The limiting range of pH of the reaction mixture by the buffer can be expressed in any range formed by any combination of the various maximum and minimum described above.
Buffers are, for example, alkali metal, alkaline earth metal or ammonium phosphates, borates, sulfates, carbonates, bicarbonates, acetates, hydroxides, bromide, silicates, citrate, gluconates and tartarates; Or alkali metal salts of lower alkancarboxylic acids (eg, acetic acid); Or basic alkali metal salts of phosphoric acid. Examples of suitable buffers also include, without limitation, sodium bicarbonate, sodium carbonate, disodium phosphate, sodium dihydrogen phosphate, sodium sapirophosphate, orthophosphates and water-soluble condensed phosphates such as tripolyphosphates and pyrophosphates. Also included are ammonium acetate, ammonium bromide, ammonium dihydrogen phosphate, ammonium hydrogen phosphate, and ammonium borate. Also included are alkali metal or alkaline earth metal compounds such as sodium, potassium and calcium compounds, for example sodium hydroxide, potassium hydroxide, calcium hydroxide, and potassium carbonate, calcium carbonate, sodium acetate, disodium hydrogen phosphate, phosphoric acid. Trisodium and sodium borate. In addition, sodium sesquicarbonate, sodium silicate, potassium silicate, sodium pyrophosphate, tetrapotassium pyrophosphate, tripotassium phosphate, trisodium phosphate, anhydrous sodium tetraborate, sodium tetraborate pentahydrate, sodium tetraborate decahydrate, magnesium oxide Boric acid, malic acid, benzoic acid, and (methyl) succinic acid.
Buffers can be added to the reaction mixture in any convenient way. For example, when ammonium salts of weak acids are used as buffers, the salts can be added directly as salts (eg ammonium acetate) or (eg For example, by adding acetic acid or acetic anhydride to excess aqueous ammonia). Typically, the buffer is present in the reaction mixture at a concentration of about 20 to about 60 weight percent based on the weight of the total reaction mixture.
Although reaction conditions, such as temperature, pressure and time, may vary depending on the choice of a particular copper source, typically the following conditions have been found to be suitable for achieving the production of the desired compound of formula (I): generally about 100 ° C. Heating reaction temperatures in the range from about 150 ° C .; Reaction pressures generally ranging from about 1.03 MPa (150 psi) to about 4.83 MPa (700 psi); And reaction times generally ranging from about 5 to about 9 hours.
In one embodiment, the DAP reaction product of the process of the invention is separated from the reaction mixture by removal of excess ammonia and a portion of water, followed by crystallization from the reaction mixture containing the reaction product, buffer and catalyst. In another embodiment, the reaction product is separated by precipitating the reaction product as hemisulfate by adding sulfuric acid to the reaction mixture.
The process of the invention advantageously provides increased selectivity for the desired product of formula (I), and increased yield thereof, compared to known methods. As used herein, the term "selectivity" for the product ("P") refers to the mole fraction or mole percentage of P in the final product mix, and the term "conversion" refers to the theoretical amount of fraction or percentage. Indicates whether the reactants have been consumed. Therefore, the conversion rate multiplied by the selectivity is equal to the maximum "yield" of P, while the actual yield, also called "net yield", is usually the loss of the sample resulting from activities such as isolation, handling, drying, etc. Will be somewhat less than this. As used herein, the term “purity” refers to what percentage of the isolated sample in water is the substance actually specified. Increased selectivity to the desired product of formula (I), and increased yield thereof obtained in the present invention from what appears to be the effect of a buffer that minimizes the occurrence of undesirable side reactions, thereby leading to an increase in selectivity to the desired product. Can be obtained. However, the present invention is not limited to any particular theory of operation.
In addition, the methods described above allow for the effective and efficient synthesis of products made from diaminopyridine, for example oligomers or polymers thereof. These materials produced may have one or more of amide functional groups, imide functional groups, or urea functional groups. Accordingly, another embodiment of the present invention provides a method for converting diaminopyridine to oligomers or polymers. Diaminopyridine can be prepared by a method such as that described above, and then further subjected to a polymerization reaction to prepare an oligomer or polymer, for example those having the above-mentioned functional group types, from the reaction. In a multistep process, polymers such as pyridobisimidazole-2,6-diyl (2,5-dihydroxy-p-phenylene) polymers can also be prepared from diaminopyridine.
Diaminopyridine is, for example, in a process in which polymerization takes place in solution in an organic compound in which the polymerization is liquid under reaction conditions, is a solvent for both diacids (halides) and diaminopyridine, and has swelling or partial relief to the polymer product. It can be converted to polyamide oligomers or polymers by reacting with diacids (or diacid halides). The reaction can be carried out at a moderate temperature, for example below 100 ° C., preferably in the presence of an acid acceptor which is also soluble in the chosen solvent. Suitable solvents include methyl ethyl ketone, acetonitrile, N, N-dimethylacetamide, dimethyl formamide-containing 5% lithium chloride,-and N-methyl pyrrolidone-quaternary ammonium chloride- Such as methyl tri-n-butyl ammonium chloride or methyl-tri-n-propyl ammonium chloride. The combination of reactant components results in the generation of significant heat, and stirring also produces thermal energy. For this reason, solvent systems and other materials are always cooled during the process when cooling is required to maintain the desired temperature. Similar methods to those described above are described in US Pat. No. 3,554,966; US Patent No. 4,737,571; And Canadian Patent 2,355,316.
Diaminopyridine can also be prepared by contacting a solution of diaminopyridine in a solvent with, for example, a solution of diacids or diacid halides, for example dichloride, in a second solvent that is incompatible with the first solvent in the presence of an acid acceptor. In processes where polymerization can result at the interface of the phase, it can be converted to polyamide oligomers or polymers by reaction with diacids (or diacid halides). Diaminopyridine can be dissolved or dispersed, for example in water containing a base, wherein the base is used in an amount sufficient to neutralize the acid produced during the polymerization. Sodium hydroxide can be used as the acid acceptor. Preferred solvents for diacids (halides) are tetrachloroethylene, methylenechloride, naphtha and chloroform. The solvent for the diacid (halide) should be relative non-solvent to the amide reaction product and relatively immiscible in the amine solvent. Preferred thresholds for immiscibility are as follows: The organic solvent should be soluble no greater than between 0.01% and 1.0% by weight in the amine solvent. Diaminopyridine, base and water are added together and stirred vigorously. The high shear action of the stirrer is important. A solution of acid chloride is added to the aqueous slurry. The contact is generally performed at 0 ° C. to 60 ° C., for example for about 1 second to 10 minutes, and preferably at room temperature for 5 seconds to 5 minutes. The polymerization takes place rapidly. Similar methods to those described above are disclosed in US Pat. No. 3,554,966 and US Pat. No. 5,693,227.
Diaminopyridine also dissolves each reagent (typically equimolar) in a common solvent and heats the mixture to a temperature in the range of 100-250 ° C. until the product has a viscosity of 0.1-2 dl / g. The process can be converted to polyimide oligomers or polymers by reaction with tetraacid (or halide derivatives thereof) or dianhydrides. Suitable acids or anhydrides include benzhydrol 3,3 ', 4,4'-tetracarboxylic acid, 1,4-bis (2,3-dicarboxyphenoxy) benzene dianhydride, and 3,3', 4, 4'-benzophenone tetracarboxylic dianhydride. Suitable solvents include cresol, xenol, diethylene glycol diether, gamma-butyrolactone and tetramethylenesulfone. Alternatively, the polyamide-acid product can be recovered from the reaction mixture and advanced to the polyimide by heating with a dehydrating agent such as a mixture of acetic anhydride and beta picoline. Similar methods to those described above are described in US Pat. No. 4,153,783; US Patent No. 4,736,015; And US Pat. No. 5,061,784.
Diaminopyridine can also be converted to polyurea oligomers or polymers by reaction with polyisocyanates, representative examples of which polyisocyanates include toluene diisocyanates; Methylene bis (phenyl isocyanate); Hexamethylene diisocyanate; Phenylene diisocyanates are included. The reaction can be carried out in solution, such as by dissolving both reagents in a mixture of tetramethylene sulfone and chloroform with vigorous stirring at ambient temperature. The product can be produced by separating with water or with acetone and water and then dried in a vacuum oven. Similar methods to those described above are disclosed in US Pat. No. 4,451,642 and Kumar, Macromolecules 17, 2463 (1984). In addition, the polyurea forming reaction can be carried out under interfacial conditions, such as by dissolving diaminopyridine in an aqueous liquid, usually containing an acid acceptor or a buffer. Polyisocyanates are dissolved in organic liquids such as benzene, toluene or cyclohexane. The polymer product forms at the interface of the two phases upon vigorous stirring. Similar methods to those described above are described in US Pat. No. 4,110,412 and in Millich and Carraher, Interfacial Syntheses, Vol. 2, Dekker, New York, 1977. Diaminopyridine can also be converted to polyurea by reaction with phosgene, for example in an interfacial process as disclosed in US Pat. No. 2,816,879.
Diaminopyridine also comprises: (i) diaminopyridine to diamino dinitropyridine, (ii) diamino dinitropyridine to tetraamino pyridine, and (iii) tetraamino pyridine to pyridobisimidazole. Pyridobisimidazole-2,6-diyl (2,5-dihydroxy-p-phenyl by conversion to -2,6-diyl (2,5-dihydroxy-p-phenylene) polymer Ren) polymers.
Diaminopyridine can be converted to diamino dinitropyridine by contact with sulfur trioxide solution in nitric acid and oleum, as discussed in WO97 / 11058. Diamino dinitropyridine is converted to tetraamino pyridine by hydrogenation using a hydrogenation catalyst in the presence of a strong acid and using a cosolvent such as lower alcohol, alkoxyalcohol, acetic acid or propionic acid, as disclosed in US Pat. No. 3,943,125. Can be switched.
Tetraamino pyridine, as disclosed in US Pat. No. 5,674,969, which is incorporated herein by reference in its entirety for all purposes, in strong polyphosphoric acid, slowly heating to greater than 100 ° C. up to about 180 ° C. under reduced pressure, 2, 5-dihydroxyterephthalic acid is polymerized with trihydrochloride-1 hydrate of tetraaminopyridine and then precipitated in water; Or by mixing the monomers at a temperature of about 50 ° C. to about 110 ° C., and then at a temperature of 145 ° C., as disclosed in US Patent Publication 2006/0287475, which is incorporated herein in its entirety for all purposes. Oligomers are formed, and then the oligomers are reacted at a temperature of about 160 ° C. to about 250 ° C. to form pyridobisimidazole-2,6-diyl (2,5-dihydroxy-p-phenylene) polymers. You can switch. The pyridobisimidazole-2,6-diyl (2,5-dihydroxy-p-phenylene) polymer thus produced is, for example, poly (l, 4- (2,5-dihydroxy) Phenylene-2,6-pyrido [2, 3-d: 5,6-d '] bisimidazole) polymer, or poly [(1,4-dihydrodiimidazo [4,5-b: 4 ', 5'-e] pyridine-2,6-diyl) (2,5-dihydroxy-1,4-phenylene)] polymer. However, its pyridobisimidazole moiety may be substituted by any one or more of benzobisimidazole, benzobisthiazole, benzobisoxazole, pyridobisthiazole and pyridobisoxazole, and 2,5- The dihydroxy-p-phenylene moiety isophthalic acid, terephthalic acid, 2,5-pyridine dicarboxylic acid, 2,6-naphthalene dicarboxylic acid, 4,4'-diphenyl dicarboxylic acid, 2,6 -Quinoline dicarboxylic acid, and at least one derivative of 2,6-bis (4-carboxyphenyl) pyridobisimidazole.
EXAMPLE
Advantageous features and effects of the invention may be seen in the examples which follow. The embodiments of the present invention on which these examples are based are merely illustrative, and the choice of these embodiments to illustrate the present invention is that materials and conditions not disclosed in these examples are not suitable for practicing the present invention, It is not intended to be excluded from the scope of the appended claims and their equivalents that are not disclosed in these examples. The significance of the examples is better understood by comparing the results obtained therefrom with the results obtained from reactions designed to provide a basis for such comparisons because they serve as a control experiment (control A) and run without buffers.
material
The following materials were used in the examples and controls. All commercial reagents were used as received unless otherwise noted. 2,6-Dichloropyridine (98% purity), CuI (99% purity), and CuBr (98% purity) were purchased from Aldrich Chemical Company (Milwaukee, WI). Cu powder (99.5% purity) was purchased from Alfa Aesar (Ward Hill, Mass.). Ammonium acetate (98% purity) was purchased from Fluka (Switzerland Buchs). Aqueous ammonia (28-30 wt.% Ammonia) was purchased from EM Science, now EMD Chemicals Inc. (Gibbstown, NJ).
Way
Unless otherwise specified, quantitative gas chromatography (HP5890 series II with FID detector) using an internal standard of triethylene glycol produced percent conversion based on the mole fraction of the starting material reacted, and the reaction produced. Yields based on the mole fraction of 2,6-diaminopyridine were measured.
The meanings of the abbreviations are as follows: "g" means grams, "GC" means gas chromatography, "h" means time, "mol" means mole, and "ml" means Milliliters, " MPa " means megapascals, " psi " means pounds per square inch.
Example 1
Preparation of (2-amino-6-chloropyridine)
In a 600 ml autoclave equipped with a gas entrapment stirrer, 240 g of aqueous ammonia (28 wt.% NH 3 ) were added and mixed with 120 g of 2,6-dichloropyridine. After purging with nitrogen, 48 g of liquid ammonia are added and the reaction mixture is heated to 150 ° C. for 6 hours under stirring. The reaction mixture was cooled to room temperature and the pressure returned to atmospheric pressure. The product was isolated by filtration, washed with water and MeOH and dried. The yield of 2-chloro-6-amino pyridine was about 70% and the purity measured by GC chromatography was 98%.
Example 2
Preparation of 2,6-dichloropyridine from 2-amino-6-chloropyridine
In a 300 ml Hastelloy autoclave, a solution of 5.0 g Cul in 120 g aqueous ammonium hydroxide (28 wt% NH 3 ) is added, 77 g ammonium acetate and 60 g 2-amino-6-chloro Mix with pyridine. After purging with nitrogen, 24 g of liquid ammonia was added, resulting in a pressure of about 0.807 MPa (117 psi). The reaction mixture was then heated to 150 ° C. for 8 hours. Over the course of the reaction, the pressure decreased from an initial pressure of 2.92 MPa (423 psi) to 2.34 MPa (340 psi). The reaction mixture was cooled to room temperature and the pressure returned to atmospheric pressure. The reaction mixture was analyzed using quantitative GC analysis method. The conversion of 2-amino-6-chloropyridine was 99.0%. The yield of 2,6-dichloropyridine was 81%.
Control group A
This reaction was carried out in the same manner as described in Example 2 except that ammonium acetate was not added to the reaction mixture. The conversion of 2-amino-6-chloropyridine was 99.5% and the yield of 2,6-diaminopyridine was 69%.
When a range of numerical values is mentioned or established herein, the range includes its endpoints and all individual integers and fractions within that range, and also those endpoints and integers therein to form a larger group of subgroups and It includes each narrower range formed therein by all possible various combinations of fractions, to the same extent as if these narrower respective ranges were explicitly mentioned. When a range of numerical values is described herein as being greater than the stated values, the ranges are nevertheless finite, and the ranges are defined at their upper limits by values operable within the context of the invention disclosed herein. Boundaries are made. When a range of numerical values is described herein as being less than the stated value, the range is nevertheless bounded by a nonzero value at the lower end of the range.
In this specification, unless expressly stated otherwise or contrary to the usage relationship, the amounts, sizes, ranges, formulations, parameters and other quantities and features mentioned herein need to be accurate, especially when modified by the term "about". Also, tolerances, conversion factors, rounding, measurement errors, etc., and other values having functional equivalents and / or operable equivalents to the values described within the context of the present invention, are within the stated values. It may be an approximation and / or larger or smaller (as desired) than what is described.
Claims (12)
(I)
Synthesis method of compound represented by the structure of:
(a) Formula II:
[Formula II]
Contacting the compound represented by the structure of with a copper source in an aqueous ammonia solution to form a reaction mixture, wherein the aqueous ammonia solution is buffered to a pH of at least about 4 and also at about 8 or less; and (b) heating the reaction mixture
{In both Formula I and Formula II, R 1 and R 2 are each independently
(a) H;
(b) alkyl, aryl or aralkyl radicals;
(c) NR 3 R 4 , wherein R 3 and R 4 are each independently
(i) H,
(ii) alkyl, aryl or aralkyl radicals,
(iii)
(iv) —C (O) —NR 5 R 5 , wherein each R 5 is as defined above; or
(d) OR 6 where R 6 is
(i) H,
(ii) an alkyl, aryl or aralkyl radical, or
(iii)
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| Application Number | Priority Date | Filing Date | Title |
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| US95325907P | 2007-08-01 | 2007-08-01 | |
| US60/953,259 | 2007-08-01 |
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| KR20100050524A true KR20100050524A (en) | 2010-05-13 |
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| EP (1) | EP2176225A1 (en) |
| JP (1) | JP2010535250A (en) |
| KR (1) | KR20100050524A (en) |
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| WO2013003708A1 (en) | 2011-06-30 | 2013-01-03 | Biomarin Pharmaceuticals, Inc. | Methods of administering 3,4-diaminopyridine |
| CN102993089B (en) * | 2012-10-11 | 2014-07-16 | 南通市华峰化工有限责任公司 | Method for synthesizing aminopyridine |
| CN102993090B (en) * | 2012-10-11 | 2014-09-03 | 南通市华峰化工有限责任公司 | Method for synthesizing 2,6-diamino pyridine |
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| DE510432C (en) | 1927-03-08 | 1930-10-18 | Schering Kahlbaum Ag | Process for the preparation of aminopyridine compounds |
| US2816879A (en) | 1951-11-15 | 1957-12-17 | Du Pont | Process for preparing polyureas utilizing immiscible phases |
| GB1135462A (en) | 1966-05-13 | 1968-12-04 | Ici Ltd | Aromatic polyamides |
| US3943125A (en) | 1974-01-31 | 1976-03-09 | Horizons Incorporated, A Division Of Horizons Research Incorporated | Substituted tetraamino heterocyclic compounds, useful in the preparation of substituted polybenzimidazoles and poly-imidazopyrrolones |
| US3966652A (en) | 1974-11-11 | 1976-06-29 | International Harvester Company | Method of making foamed copolyimides and product obtained therefrom |
| US4068050A (en) | 1976-05-17 | 1978-01-10 | Cpc International Inc. | Difunctional terminated macromolecular monomers and condensation copolymers produced therefrom |
| JPS5953910B2 (en) | 1976-10-25 | 1984-12-27 | 住友化学工業株式会社 | Manufacturing method of aminopyridines |
| US4451642A (en) | 1981-05-21 | 1984-05-29 | E. I. Du Pont De Nemours And Company | Bis(aminoneopentyl) aromatics and polyamides derived therefrom |
| FR2514772B1 (en) | 1981-10-19 | 1985-09-06 | Inst Francais Du Petrole | REACTIVE COMPOSITIONS OF THERMOSTABLE POLYIMIDES WITH HIGH SOLUBILITY AND USES THEREOF |
| JPS5953910A (en) | 1982-09-21 | 1984-03-28 | Aisin Seiki Co Ltd | Vehicle speed control device |
| US4737571A (en) | 1986-01-17 | 1988-04-12 | E. I. Du Pont De Nemours And Company | Preparation of aromatic polyamide with solvent system comprising N-alkyl substituted amide and quaternary ammonium compound |
| US5061784A (en) | 1990-08-06 | 1991-10-29 | Hoechst Celanese Corporation | Polymers prepared from 4,4'-bis(3,4-dicarboxyphenyl) hexafluoroisopropyl) diphenyl dianhydride |
| US5674969A (en) | 1993-04-28 | 1997-10-07 | Akzo Nobel Nv | Rigid rod polymer based on pyridobisimidazole |
| US5693227A (en) | 1994-11-17 | 1997-12-02 | Ionics, Incorporated | Catalyst mediated method of interfacial polymerization on a microporous support, and polymers, fibers, films and membranes made by such method |
| NL1001238C2 (en) | 1995-09-19 | 1997-03-20 | Akzo Nobel Nv | Nitration of pyridine-2,6-diamines. |
| TW562823B (en) | 1999-10-21 | 2003-11-21 | Teijin Ltd | Process for producing meta-aromatic polyamide filaments |
-
2008
- 2008-08-01 KR KR1020107004351A patent/KR20100050524A/en not_active Application Discontinuation
- 2008-08-01 EP EP08782583A patent/EP2176225A1/en not_active Withdrawn
- 2008-08-01 WO PCT/US2008/071869 patent/WO2009018504A1/en active Application Filing
- 2008-08-01 CN CN200880101241A patent/CN101765588A/en active Pending
- 2008-08-01 JP JP2010520212A patent/JP2010535250A/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| JP2010535250A (en) | 2010-11-18 |
| CN101765588A (en) | 2010-06-30 |
| WO2009018504A1 (en) | 2009-02-05 |
| EP2176225A1 (en) | 2010-04-21 |
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