AU620245B2 - Creación de Inventos y Patentes con Inteligencia Artificial

AU620245B2 – An improved process for the preparation of 3,5,6- trichloropyridin-2-ol
– Google Patents

AU620245B2 – An improved process for the preparation of 3,5,6- trichloropyridin-2-ol
– Google Patents
An improved process for the preparation of 3,5,6- trichloropyridin-2-ol

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AU620245B2

AU620245B2
AU54945/90A
AU5494590A
AU620245B2
AU 620245 B2
AU620245 B2
AU 620245B2
AU 54945/90 A
AU54945/90 A
AU 54945/90A
AU 5494590 A
AU5494590 A
AU 5494590A
AU 620245 B2
AU620245 B2
AU 620245B2
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Prior art keywords
chloride
trichloropyridin
organic solvent
temperature
reaction
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1989-05-12
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AU5494590A
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R. Garth Pews
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Dow Chemical Co

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Dow Chemical Co
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1989-05-12
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1990-05-11
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1992-02-13

1990-05-11
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1990-11-15
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1992-02-13
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1992-02-13
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C—CHEMISTRY; METALLURGY

C07—ORGANIC CHEMISTRY

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

C—CHEMISTRY; METALLURGY

C07—ORGANIC CHEMISTRY

C07D—HETEROCYCLIC COMPOUNDS

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

C07D213/62—Oxygen or sulfur atoms

C07D213/63—One oxygen atom

C07D213/64—One oxygen atom attached in position 2 or 6

C—CHEMISTRY; METALLURGY

C07—ORGANIC CHEMISTRY

C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS

C07C255/00—Carboxylic acid nitriles

C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms

C07C255/19—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms containing cyano groups and carboxyl groups, other than cyano groups, bound to the same saturated acyclic carbon skeleton

Abstract

A process for the preparation of 3,5,6-trichloropyridin-2-ol from trichloroacetyl chloride and acrylonitrile is improved by separately conducting the individual addition, cyclization and aromatization steps. By separating these steps, water and HCl, which are by-products of the latter steps, can be precluded from interfering with the earlier steps. The individual process steps have also been improved.

Description

AUSTRALIA
Patents Act V 4 COMPLETE SPECIFICATION
(ORIGINAL)
Class Int. Class Application Number: Lodged: Complete Specification Lodged: Accepted: Published: Priority Related Art: o o 000 0 0000 0 0000 0000 0 0 S0 0 00 0 6000 8 a 00 Q
I
0 O C O 00 o C C CCC C
CCOCC
C C C~t~ 0 C Applicant(s): The Dow Chemical Company 2030 Dow Center, Abbott Road, Midland, Michigan 48640, UNITED STATES OF AMERICA Address for Service is: PHILLIPS ORMONDE FITZPATRICK Patent and Trade Mark Attorney.
367 Collins Street Melbourne 3000 AUSTRALIA Complete Specification for the invention entitled: AN IMPROVED PROCESS FOR THE PREPARATION OF 3,5,6-TRICHLOROPYRIDIN-2-OL Our Ref 166018 POF Code: 1037/1037 The following statement is a full description of this invention, including the best method of performing it known to applicant(s): 6006 6006 AN IMPROVED PROCESS FOR THE PREPARATION OF 6-TRICHLOROPYRIDIN-2-OL o The present invention concerns an improved 0000 process for preparing 3,5,6-trichloropyridin-2-ol ro ~0000 trichJloroacetyl chloride and acrylonitrile.
000 000 000 0 5 3,5,6-Trichloropyridin-2-ol. is an intermediata 0 00 oc’ 00 in the manufacture of several agricultural pesticides, chlorpyrifos, chlorpyrlfos-methyl and triclopyr.
U.S. Patent 4,327,216 describes a proc.9ss for preparing a mixture of 2 ,3,5, 6 -tetrachloropyridine and 3,5,6- .000 10~ 0000 a-trichloropyridin-2-ol by reacting tric1hloroacety.
«0000 Go0 chloride with acrylonitrile in the presence of a catalyst.
The following series of reactions is r s o s b e f r t e p o u t b a n d i a d p t n (Scheme I).
0 36, 327-F -JX -2-
I
4 Schemel AC1
CN
CH CC1 3 -1 T- C1 o0 ‘I N 0 0 a 0 0000 0 9 15 C ccC0 0c
C
C C 0 C ‘,e C1
H
HO,7JN C1N C1
-H
2 0 I -HCI C1 C’ N1C
-HCI
H
I-
HCI
C
C C C C 0C 0 C C CC C r
C
Although the series of reactions is advantageously 30 carried out in a single operation and in a closed system under pressure, the combined yield of 2,3,5,6-tetrachioropyridine and 3,5,6-trichloropyridin-2-ol is not very high. Furthermore, the reaction typically produces a mixture of’ the two products which must be separated or treated in subsequent operations to convert one product into the other. It is desirable to have a process to 36,327-F– -2i- 3~ prepare 3,5,6-trichloropyridin-2-ol in higher yieijs and without any tetrachloropyridine by-product.
The present invention is directed to an improved process for preparing 3,5,6-trichloropyridin-2- -ol which comprises the following steps: cc cCC coo cccc C Ct.
CCC C reacting trichloroacetyl chloride with acrylonitrile at a temperature from 50 to 140°C in the presence of a catalytic amount of copper or a cuprous salt to produce 2,2,4t richloro-4-cyanobutanoyl chloride while removing any HC1 formed by operating under reflux conditions; reacting the 2,2,4-trichloro-4-cyanobutanoyl chloride in an inert organic solvent with anhydrous HC1 at a pressure from 136 to 1,480 kPa and at a temperature from ambient to 100°C to cyclize the butanoyl chloride to 3,3,5,6-tetrachloro- -3,4-dihydropyridin-2-one; and reacting the 3,3,5,6-tetrachloro-3,4- -dihydropyridin-2-one with chloride ion in an inert organic solvent to produce the 3,5,6-trichloropyridin-2-ol.
CC C C Ct CC C
CC
C C CC c Crc C The present invention is further directed to the various process improvements as they relate to the individual steps.
It has been found that 3,5,6-trichloropyridin-2-ol can be prepared in high yield and without tetrachloropyridine as a by-product by conducting the 36,327-F -3additirnn, cyclization and aromatization reactions separtu -,ly.
Addition: CC1 3
CI
CN
CH 2 C1 C1 0I~ Cyclization: Go a~ 00 0 00000 00000 0 0 0 00 0 0000 15 0 0000 0 00D 0 0 0 000 a C1 C1 0N C N Aromatization: 0000 0 0000 00 OC Ic 10 C
I
O 0 C 000 C c C C C C C CCC CCC c C CI1 C1C N 0 The first reaction, the addition reaction of trichioroacetyl chloride to acrylonitrile produces 2,2,4-trichloro-4L{eyanobutanoyl chl~oride, which cyclizes in the presence of 801. The cyclization intermediate, 3 0 depending oa- whether 801 or H{ 2 0 is eliminated, can yield one of three products: 3,,,-ercloo34dhdo pyridin-2-one; 3,5,6-trichloropyridin-2-ol; or 2,3,5,6- -tetr’achloropyridine.
It has now been found tL-hat the water produced during the formation of the tetrachioropyridine Is a 36, 327-F-4 r; major contributor to yield loss via numerous side reactions. Water can be formed during the cyclization process which itself is acid catalyzed. The present invention provides a process for achieving better yields by removing any HC1 formed by decomposition of the reactants during the addition step. For convenience, HCL is removed and hence water formation is precluded by preferentially conducting the addition reaction under reflux.
Trichloroacetyl chloride (TCAC) and SOOo acrylonitrile (VCN) are items of commerce and are oo o oo routinely distilled prior to use. The trichloroacetyl 0.00 chloride and acrylonitrile can be reacted in molar 0000o 0 00 0° 15 ratios ranging from stoichiometric, 1:1, to a 2 to Qoo 3 fold excess of either reagent, 1:3 to 3:1 o o VCN/TCAC. Ratios of VCN/TCAC of 1.1 to 1.3 are ooo 0 generally preferred.
The addition reaction is carried out in the 0oo presence of a catalytic amount of a cuprous salt under ooo an inert atmosphere, such as, for example, nitrogen or argon. Cuprous salts that can be employed include, for s 0 I example, the chloride, bromide, iodide, oxide or 0G 0 C acetate, preferably the halides. Catalysts that are partially oxidized to the cupric oxidation state or are C, hydrated are less effective than the pure materials.
c S The addition of copper metal, which itself can be Soxidized to the cuprous oxidation state while a 30 simultaneously preventing further oxidation to the cupric oxidation state, can advantageously be employed.
The cuprous catalyst is usually employed in an amount corresponding to from 0.005 to 0.05 moles of catalyst 36,327-F -6per mole of trichloroacetyl chloride, although larger proportions can be used.
The addition reaction may be carried out neat or in the presence of an inert solvent. Alkylnitriles, such as acetonitrile, are commonly used for the cuprous catalyzed addition of polyhalogen compounds to olefins.
However, the addition of acetonitrile to the reaction mixture does not provide any beneficial effects.
Therefore, the reaction is preferably conducted neat or with excess TCAC or VCN effectively serving as the o solvent. Trichloroacetyl chloride can be commercially 00; o prepared by the photochemical oxidation of perchloroethylene; see, for example, U.S. Patent 2.427,624.
Oa 0 o9 15 Prepared by this procedure, TCAC typically contains 6,o about 15 percent residual perchloroethylene. Perchloro- 06 iethylene has no negative effect on the addition chemistry.
To prevent the production of HC1 by the S» premature cyclization of 2,2,4-trichloro-4-cyanobutanoyl chloride, reaction temperatures should be maintained from 50 to 140 0 C. To remove any HC1 produced ST2, by the decomposition of TCAC, the reaction is run at reflux. The reflux temperature is determined by the composition of the mixture. Ideally, the temperature should be maintained between 70-120°C, preferably Sbetween 80-105 0 C. The preferred temperatures are 0 conveniently between the boiling points of VCN and TCAC a 30 at atmospheric pressure. When the reaction is conducted neat or with VCN or TCAC in excess as an effective solvent, the reflux temperature gradually increases as 36,327-F -6-
L~-
:r i -7the lower boiling reactants are converted to higher boiling product.
The addition reaction is preferably conducted under an inert atmosphere, such as, for example, under a nitrogen or argon blanket. Although conveniently conducted at atmospheric pressure, the reaction is Spreferably run under a slight positive pressure of up to 136 kPa (5 psig) of the blanketing inert gas which helps in keeping the reaction mixture dry.
In a typical reaction, freshly distilled TCAC, coo VCN and anhydrous CuCl are heated under reflux in a nitrogen atmosphere. After the addition reacticn is complete, generally in from 8 to 48 hours (hrs), the 15 O. product 2,2,4-trichloro-4-cyanobutanoyl chloride can be 0000 o oO recovered by conventional techniques. The product can oo o be conveniently isolated, for example, by evaporating any volatile TCAC or VCN, adding a suitable solvent in which the spent copper catalyst is not soluble and in aoQ1 which the subsequent cyclization reaction can be 0,0 advantageously conducted, and removing the catalyst by 0 a t t filtration. Suitable solvents include aromatic a C. hydrocarbons, halogenated hydrocarbons and carboxylic acid esters. Product of greater than 90 percent purity can be obtained by evaporation of the solvent.
coL Alternatively, the filtrate so obtained can be used a directly in the subsequent cyclization reaction.
The cyclization of 2,2,4-trichloro-4-cyanobutanoyl chloride to 3,3,5,6-tetrachloro-3,4-dihydropyridin-2-one is catalyzed by acidic reagents, preferably in an anhydrous state. The cyclization is conveniently carried out, for example, by reacting the 2,2,4-trichloro-4-cyanobutanoyl chloride with anhydrous 36,327-F -7- TT- HC1. Simply sparging anhydrous HC1 into the 2,2,4- -trichloro-4-cyanobutanoyl chloride at atmospheric pressure in the absence of a solvent does not accomplish cyclization. Since higher temperatures lead to greater amounts of dehydration and tetrachloropyridine formation, it is beneficial to keep the temperature below 100 0 C. The cyclization reaction is effectively run from ambient temperature to 100 0 C, preferably from 400 to 60°C. In order to keep the reaction mixture mobile at temperatures below the melting point of the product and in order to keep the anhydrous HC1 in So°Oo effective contact with the reaction mixture, it is 0 o0 00oo preferable to conduct the cyclization under pressure in the presence of a solvent. Pressures from 136 to 1,180 0 0 0 00 0 15 kPa (5 to 200 psig) are routinely employed; those from ooo 273 to 1,135 kPa (25 to 150 psig) are preferred.
0 00 o0 0 000 0 Suitable solvents for the cyclization reaction include aromatic hydrocarbons, halogenated hydrocarbons and carboxylic acid esters. Examples of suitable o0*»0 solvents of each class include but are not limited to ooo o».o the following: toluene and xylenes; methylene chloride, o00 ethylene dichloride (EDC) and perchloroethylene (PERC); o oo and ethyl acetate.
000° The cyclization reaction may be conveniently .0 conducted in a batch reaction or in a continuous fashion 000000 So in a coil reactor. In a typical reaction, 2,2,4-tri- 000000 o olo chloro-4-cyanobutanoyl chloride is diluted with the 60000 30 desired solvent in a closed pressure vessel, and the vessel is pressurized with anhydrous HC1 to the desired pressure. The reaction mixture is stirred at the appropriate temperature until the reaction is completed, usually from one to three hours. The reaction vessel is vented and the product, 3,3,5,6-tetrachloro-3,4- 36,327-F __1 I _III~_ -9- -dihydropyridin-2-one, can be isolated by conventional procedures. For example, evaporation of the solvent provides a crude solid product which can be slurried with an aliphatic hydrocarbon, such as hexane, ind which can then be isolated by filtration. Product so obtained is sufficiently pure after drying to be used in the subsequent aromatization. Alternatively, the crude reaction mixture can be used directly, immediately after venting and removal of the HC1.
The aromatization of 3,3,5,6-tetrachloro-3,4t i -dihydropyridin-2-one to 3,5,6-trichloropyridin-2-ol can cc be accomplished in a variety of ways. Among the most effective procedures are treatment in a two-phase system S, 15 with an aqueous base or treatment with chloride ion in SC» an organic solvent.
SSince the desired product, 3,5,6-trichloropyridin-2-ol, is often used as the sodium salt, it is often convenient to conduct the aromatization with c cC Caqueous alkaline solutions. The reaction is preferably rc run in a two-phase system using a water immiscible i t organic solvent. Suitable solvents for the aromati- Sczation reaction include aromatic hydrocarbons, halogenated hydrocarbons and carboxylic acid esters.
i Sxamples of suitable solvents of each class include but j are not limited to the following: toluene and xylenes; methylene chloride, ethylene dichloride and percnloroethylene; and ethyl acetate. Naturally, it is preferable to employ the same solvent that has previously been used in the cyclization reaction.
The aromatization reaction requires the use of at least two equivalents of base per equivalent of 3,3,5,6-tetrachloro-3,4-dihydropyridin-2-one. One 36,327-F -9nr- equivalent is required for the elimination of one mole of HC1, while the second equivalent is consumed in converting the pyridinol to the pyridinate. If desired, larger proportions of base may be employed. Suitable K bases include but are not limited to the alkali metal hydroxides and carbonates. Sodium or potassium carbonate are generally preferred, particularly for the carboxylic acid ester solvents which are susceptible to reaction with dilute caustic at room temperature.
In a typical reaction, the base, dihydroa o0 pyridone, solvent and water are contacted with stirring oo00 at a temperature of from ambient to 100°C or the reflux 0000 temperature of the mixture. After the reaction is 00oo 0 0 00o 15 complete, generally in from 2 to 24 hrs, the 3,5,6- 0090 ooo 1-trichloropyridin-2-ol is isolated by conventional procedures. For example, trichloropyridinol may simply be isolated by acidifying the reaction mixture and separating the organic phase. After dryiing the organic solution, evaporation of the solvent provides the desired pyridinol. Alternatively, if the alkali metal t salt of the trichloropyridinol is desired, an aqueous solution of the pyridinate may be obtained by simply 5 separating the aqueous reaction phase.
Alternatively, the aromatization reaction can 0oc. be accomplished by treating the 3,3,5,6-tetrachloro-3,4o -dihydropyridin-2-one with chloride ion in an inert C C organic solvent, The chloride ion may be added directly eym 30 Sor may be generated insitu by initiating the elimination of HCI from the pyridone. Since chloride ion is generated by the elimineion of HC1 from the substrate, only catalytic quantities of ohlo-ide ion or of a material capable of initiating the elimination of HC1 are n.lded. Suitable catalystc contemplated by the 36,327-F
I
-11- 00 0 00 0 o 0000 0 0000 0 00D 00 00000 0 0 00 0 0 00 00ooo0 0 0 0 o00o 000 0 0o 0 0 0000oooo 0 a above definition include but are not limited to the following types of materials: tertiary or aromatic amine bases, such as, for example, trialkyl amines, pyridine, picolines or lutidines; quaternary ammonium or phosphonium salts, such as, for example, t traalkyl or aryl ammonium or phosphonium halides; crown ether complexes, such as, for example, 18-Crown-6/KCl; and ion exchange resins, particularly amine resins such as, for example, MSA-1 Dow Ion Exchange Resin. Specific examples of suitable materials include the following: tetrabutylammonium halides, tetraphenylphosphonium halides, nonyltriphenylphosphonium halides, benzyltriethylammonium halides, pyridinium halides and poly (4-vinylpyridine). MSA-1 Dow Ion Exchange Resin and 15 tetrabutylammonium chloride are among the preferred catalysts. These catalysts are usually employed in an amount corresponding to from 0.002 to 0.2 moles of catalyst per mole of 3,3,5,6-tetrachloro-3,4- -dihydropyridin-2-one, preferably from 0.005 to 0.05 20 moles of catalyst per mole of dihydropyridone.
Suitable solvents for the aromatization reaction include the same aromatic hydrocarbons, halogenated hydrocarbons and carboxylic acid esters 25 2 employed in the previous steps. Perchloroethylene is a particularly preferred solvent for this reaction.
The reaction is conducted at a temperature from between 40° to 120 0 C, preferably at the reflux temperature of the mixture.
In a typical reaction, the 3,3,5,6-tetrachloro- -3,4-dihydropyridin-2-one is contacted with the catalyst and solvent, and the reaction mixture is heated to reflux. After the reaction is complete, generally in 36,327-F -11- -12from 1 to 3 hrs, the desired 3,5,6-trichloropyridin-2- -ol can be isolated by conventional techniques. For example, if an insoluble catalyst such as MSA-1 Dow Ion i Exchange Resin is employed, the catalyst can be removed i by filtration while hot and can be recovered and 5 recycled in subsequent reactions. After the removal of i the catalyst, the reaction solution can be cooled to crystallize the trichloropyridinol which is then isolated by filtration. If a soluble catalyst such as tetrabutylammonium chloride is used, the reaction solution can be cooled to crystallize the trichlr o- Is pyridinol which is isolated by filtration. Th, filtrate containing the soluble catalyst can be recycled I directly.
The present invention is illustrated by the following examples; however, these examples should not be construed as a limitation on the scope of the present claims, at C I Sot 36,327-F 5 1 1 -~LL -r s.a-.~aii~ -13- Example 1 Addition of Trichloroacetyl Chloride to Acrylonitrile CI
H
Cl H
CC
3 Cl +CH 2 C CI
CI
0 CIC N TCAC
VCN
0 0B 0 0 t 000 0 0000 0 0000 00 0 00 1 Freshly distilled trichloroacetyl chloride 0o:0 (TCAC), acrylonitrile (VCN) and anhydrous catalyst were 0000 0 o, heated under reflux in a nitrogen atmosphere. Percent S 000 0 conversion was determined by withdrawing, cooling, filtering and analyzing samples by gas chromatography (GC) or nuclear magnetic resonance (NMR) spectroscopy.
oOO. Product was isolated by cooling the reaction mixture, o°»o evaporating the volatile starting materials and removing Sthe catalyst by filtration. The results are summarized So, in Table I.
25 8 36,327-F -13f- 00a 0 0 0 000 00 0 0 0 0 0 0 00 000 00 000 0 0 0 00 000 00 00 broo ga~o =0 00 0 0 00 000 0 00 0 Table I PREPARATION OF 2,2, 4-TRICHLORO-4-CYANOBUTANOYL CHLORIDE FROM TRICHLOROACETYL CHLORIDE (TCAC) AND ACRYLONITRILE (VCN) TCAC VCN Catalyst (grams) Time Yield (moles) (moles) (hrs) (moles) (moles) Cu, CuCl Analysis Isolated 0.5 1.12 44 69 0.5 2.24 48 )95 0.5 4.48 45 94 1.0 2.24 24 1.5 2.2 24 78 0.4 2.24 48 77 0.4 1.45 2.24 24 76 0.4 2.90 24 66 0.48_ 0.3 1.90 2.24 16 59 58 0.48a 0.38 1.90 2.24 16 59 61 0.494 0.49 1.90 2.24 9 50 53 0.48″ 0.30 1.90 2.2b) 12 51 52 0.48 0.39 1.45 2.24 10 45 0.48 0.49 1.45 2.24 10 51 48 0.48 0.59 1-45 2.24 10 65 62 0.48 0. 1.45 2.24 10 67 66 TCAC contains an aidditional 15 Srecycle WT% perchloroethylene -i ii i
(I
Example 2 Cyclization of 2,2,4-Trichloro-4- -Cyanobutanoyl Chloride CI H CI Cl C Cl
CI
C N C N O
H
H
tt s The cyclizations were carried out in a 600 oC milliliter (mL) Hastelloy C Bomb equipped with a magnetic drive. The 2,2,4-trichloro-4-cyanobutanoyl chloride was diluted with the desired solvent and the c bomb pressurized with anhydrous HC1 to the desired pressure. After stirring for the indicated time the bomb was vented and the contents transferred to a round bottom flask for evaporation on a rotary evaporator.
t 20 The contents Jere slurried with hexane to facilitate $itt isolation by filtration. The results are summarized in Table II.
C t t t t C C c 36,327-F CHLORIDE TO 3,3,5,6-TETRACHLORO-3,4-DIHYDROPYRIDIN- CYLIAT~r~ F ,2)4TRCHOR-L2CANBUANY I C I 9 C a C t C Solvent Temp 0 C Time Pr’essure HC1 tY ielId (hrs) psig (kPa)
EDC
1 51 14o 93 EDC1)2 5 0 70 92 ED1 252.al0 (70 97 EDCO2 2010 70 97 ethylene dichloride Example 3 Aromatization of 3,3,5,6-Tetrachlor-3,1- -Dihydropyridin-2-one: Two-Phase System 20C’ N 0 C1 N
OH
H
In a typical experiment 23.3 grams (0.1 mol) of the di1hydropyr idone, 233 mL ethyl acetate, 233 mL water and 0.3 mol of base were stirred (magnetic stirrer) and refluxed for 2 hrs. After cooling, the reaction mixture was acidified with concentrated UCl and the organic phase separated and dried over MgS04. After filtration, the product was obtained by evaporation of the solvent from the filtrate. *The results are summarized in Table III.
36, 327-F -6 -16-
JWF
-17- TABLE III AROMATIZATION OF 3,3,5,6-TETRAC-LORO-3,14- -DIHYDROFYRIDIN-2-ONE TO 3,5,6-TRICHLOROPYRIDIN-2-OL IN AN AQUE OUS TWO- PHASE SYSTEM Base Thrme Solvents Temp /Yield NaOH 20+ EDC11/h 2 O ambient 100 Na 2
CO
3 20 EA 0
)/H
2 0 ambient 98 Na 2
CO
3 20 EA 0
W/H
2 0 ambient 97 Na 2
CO
3 2 EAb)/H 2 0 reflux 914 Wa P CO 3 EA )/H 2 0 ref lux 914 o 0 t 0 00 0 000 0 o* 0 00000 0 000 00 0 00 a 0 a fc 0ethylene dichloride 0) ethyl. acetate Example 14 Aromatization of 3,3,5,6-Tetrachloro-3, 1 4- -Dihydropyridin-2-one: Nonaqueous To a 25 mL three neck round bottom flask was added 5 g of 3,3’5D,6-tetrachloro-3,4-dihydropyridin2- -one, 0.1 g of catalys. and 25 mL of solvent. The reaction mixture was heated to reflux and reaction was monitored by GC. Product was recovered by filtration. In each instance isolated yields were at least 90 percent. Table IV summarizes the catalysts and solvents employed.
0 00 C CC I C
C
00(0(0 I I «Iva, 327-F’-7 -17- -18- 0 00 0 0 0 00909 0000 00.
a000 00 0 0,O 0000 0 00 0 0 0 ago0 0 Table IV CATALYSTS AND SOLVENTS EMPLOYED IN NONAQUEOUS AROMATIZATION OF 3,3,5,6-TETRACHLORO-3,L4- -DIHYDROPYRIDIN-2-ONE Catalyst Solvent 2-picoline toluene 2,6-lutidine o-xylene Tetrabutylarr~nonium f luoride perchioroethylene Tetrabutylammonium, chloride» perchloroethylene Tetrabutylammonium bromide perchioroethylene Tetrabutylammonium, iodide perchloroethylene Tetrabutylammonium. cyanide perchloroethylene Tetraphenylphosphonium chloride perchioroethylene Tetraphenylphosphonium bromide perchloroethylene Tetrabutylphosphonium acetate perchloroethylene n-Nonyltriphenylphosphonium perchioroethylene bromide MSA-1 Dow Ion Exchange Resin) perchloroethylene Benzyltriethylammonium chloride perchloroethylene Pyridinium chloride perchioroethylene Poly 2 4-vinylpyridine) perchloroethylene 1 8-Crown-6 /KCl perchloroethylene 0 0*4 20 er t C a recycled 5 times recycled 10 times r, Example 5 Consecutive Cyclization-Aromatization The cyclizations were carried out in a 600 mL Hastelloy C bomb equipped with a magnetic drive. The 2,2,Ll-trichloro-i4-cyanobutanoyl chloride (ADDUCT) was diluted with 150 mL of’ perchloroethylene and the bomb 36,327-F -8 -18- I_ _ICL_ i i i I was pressurized to 150 psig (1,135 kPa) with anhydrous HC1. After stirring for 2 hrs at the indicated temperature, the bomb was vented and the contents transferred with the aid of an additional 100 mL of perchloroethylene to a round bottom flask containing MSA-1 Dow Ion Exchange Resin. The mixture was refluxed for 1.5 hrs and the solid catalyst was removed by filtration while hot. The filtrate was cooled to crystallize the 3,5,6-trichloro-pyridin-2-ol which was isolated by filtration and dried. The results are summarized in Table V.
TABLE V Cyclization-Aromatization Cyolization Aromatization Adduct TempoC MSA Resin %Yield 61 250 3.2 86 72 500 3,2 87 64 500 3.2 91 0008 0 8 CC C
CC
CC
CC 0 C4 t CC C 36,327-F -19-

Claims (5)

1. A process for the preparation of 2,2,4- -trichloro-4-cyanobutanoyl chloride which comprises reacting trichloroacetyl chloride with acrylonitrile at a temperature from 50 to 140°C in the presence of a catalytic amount of copper or a cuprous salt while removing any HC1 formed by operating under reflux conditions.

2. The process according to Claim 1 which is performed from atmospheric pressure to a slight positive pressure of up to 136 kPa.

3. A process for the preparation of 3,3,5,6- -tetraohloro-3,4-dihydropyridin-2-one which comprises reacting 2,2,4-trichloro-4-cyanobutanoyl chloride in an inert organic solvent with anhydrous HC1 at a pressure from 136 to 1,480 kPa and at a temperature from ambient to 1000C.

4. The process according to Claim 3 in which the inert organic solvent is an aromatic hydrocarbon, a halogenated hydrocarbon or a carboxylic acid ester. A process for the preparation of 3,5.6- -trichloropyridin-2-ol which comprises reacting 3,3,5,6- 36,327-F

11–ssl11113 ~1113111 11 r r I V-id~n 00 0 o oo 0 00 0 0 0 I o o& i ooo o0o 0 00 0 000 0 1 o0 -21- -tetrachloro-3,4-dihydropyridin-2-one with chloride ion in an inert organic solvent. 6. The process according to Claim 5 in which the chloride ion is generated in situ by elimination of HC1 from the dihydropyridone. 7. The process according to Claim 5 or 6 in which the inert organic solvent is an aromatic hydrocarbon, a halogenated hydrocarbon or a carboxylic acid ester. 8. The process according tn any one of Claims 5-7 in which the reaction is conducted at a temperature from 40 0 to 120 0 C. 9. An improved process for the preparation of 3,5,6-trichloropyridin-2-ol which comprises the following steps: reacting trichloroacetyl chloride with acrylonitrile at a temperature from 50 to 140°C in the presence of a catalytic amount of copper or a cuprous salt to produce 2,2,4-trichloro-4-cyanobutanoyl chloride while removing any HC1 formed by operating under reflux conditions; reacting the 2,2,4-trichloro-4-cyano- butanoyl chloride in an inert organic solvent with anhydrous HC1 at a pressure from 136 to 1,480 kPa and at a temperature from ambient to 100°C to cyclize the butanoyl chloride to 3,3,5,6-tetrachloro- -3,4-dihydropyridin-2-one; and a l t6 %0e 0 C ~a~ 36,327-F -21- -22- reacting the 3,3,5,6-.tetrachloro-3,4- -dihydropyridln-2-one with chloride ion in an inert organic solvent to produce the 6-trichloropyridin-2-ol. DATED: 23 March, 1990 THE DOW CHEMICAL COMPANY V By teir aten Attrne thei PaetPonys~ PHILLIPS ORMONDE FITZPATRICK C 36 327-F -2 -22-

AU54945/90A
1989-05-12
1990-05-11
An improved process for the preparation of 3,5,6- trichloropyridin-2-ol

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1989-05-12

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Families Citing this family (13)

* Cited by examiner, † Cited by third party

Publication number
Priority date
Publication date
Assignee
Title

IL86341A
(en)

1988-05-11
1992-02-16
Pamol Ltd
Preparation of polychloropyridine derivatives and intermediates therefor

US5254712A
(en)

1990-01-06
1993-10-19
Stamicarbon B.V.
Process for the preparation of 5-oxohexane nitriles and the compound 2,4-dimethyl-5-oxohexane nitrile

NL9000034A
(en)

1990-01-06
1991-08-01
Stamicarbon

PROCESS FOR THE PREPARATION OF 5-OXOHEXANE NITRILLES AND THE SUBSTANCE 2,4-DIMETHYL-5-OXOHEXANE NITRILLES.

US5618942A
(en)

1993-09-03
1997-04-08
Luxembourg Industries (Pamol) Ltd.
Production of 2,3,5,6-tetrachloropyridine

US5688953A
(en)

1996-07-31
1997-11-18
Dowelanco
Process for the preparation of 3,3,5-trichloroglutarimide

CN102351785B
(en)

2011-08-11
2013-05-01
江苏九九久科技股份有限公司
Method for preparing 3, 5, 6-trichloropyridin-2-ol sodium

CN103086961A
(en)

2011-10-27
2013-05-08
山西三维丰海化工有限公司
Method for producing pyridone from chloroacetic acid waste liquid

CN103086959A
(en)

2011-10-27
2013-05-08
山西三维丰海化工有限公司
Novel process for producing 3,5,6-sodium trichloropyrindinol

CN103086960A
(en)

2011-10-27
2013-05-08
山西康得利精细化工有限公司
Novel process for producing chlopyrifos from pyridone by using aqueous phase method

CN103193705A
(en)

2013-03-22
2013-07-10
浙江工业大学
Synthesis method of 2-chloronicotinic acid and derivative thereof

CN103274996B
(en)

2013-05-02
2015-08-19
江苏九九久科技股份有限公司
The one kettle way of improvement prepares the method for 3,5,6-trichloropyridine-2-sodium alkoxide

CN103819397B
(en)

2014-03-14
2015-12-30
杨雪飞
A kind of efficient catalytic synthetic method of heterocyclic alcohol

CN104876858A
(en)

2015-05-13
2015-09-02
安徽国星生物化学有限公司
One-pot method for synthesizing sodium 3,5,6-trichloropyridin-2-olate

Citations (3)

* Cited by examiner, † Cited by third party

Publication number
Priority date
Publication date
Assignee
Title

EP0030214A2
(en)

1979-11-30
1981-06-10

Ciba-Geigy Ag

Process for the preparation of 2,3,5,6-tetrachloropyridine and 3,5,6-trichloropyridin-2-ol

US4469896A
(en)

1981-08-17
1984-09-04

Ciba-Geigy Corporation

Process for the production of chloropyridines substituted by methyl, trichloromethyl or trifluoromethyl groups

EP0341585A1
(en)

1988-05-11
1989-11-15

Luxembourg Industries (Pamol) Ltd.

Production of 3,5,6-trichloro-pyridin-2-ol and novel intermediates thereof

Family Cites Families (7)

* Cited by examiner, † Cited by third party

Publication number
Priority date
Publication date
Assignee
Title

US3007931A
(en)

1959-03-09
1961-11-07
Phillips Petroleum Co
Production of unsaturated heterocyclic nitrogen bases

US4245098A
(en)

1978-12-05
1981-01-13
Ciba-Geigy Corporation
Process for producing 2,3,5-trichloropyridine, 2,4,4-trichloro-4-formyl-butyronitrile as a novel compound and a process for producing it

US4435573A
(en)

1982-10-25
1984-03-06
The Dow Chemical Company
Process for the preparation of substituted pyridines

US4468354A
(en)

1983-02-15
1984-08-28
The Dow Chemical Company
Continuous process for preparing 5-oxo-2,4-dichloro-4-substituted pentanenitriles

US4465186A
(en)

1983-07-14
1984-08-14
Meyers Jonathan H
Holder for clips

AR243869A1
(en)

1987-06-05
1993-09-30
Quimica Estrella Aca Sa
A procedure for synthesising 2-hydroxy-3,5,6-trichloropyridine.

JPS63313771A
(en)

1987-06-15
1988-12-21
Nippon Kayaku Co Ltd
Production of 3,5,6-trichloro-2-pyridinol

1989

1989-05-12
US
US07/350,961
patent/US4996323A/en
not_active
Expired – Lifetime

1990

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patent/BR9001798A/en
not_active
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patent/NZ233615A/en
unknown

1990-05-11
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CN90102727A
patent/CN1027259C/en
not_active
Expired – Lifetime

1990-05-11
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AU54945/90A
patent/AU620245B2/en
not_active
Expired

1990-05-11
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KR1019900006675A
patent/KR0153446B1/en
not_active
IP Right Cessation

1990-05-11
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HU903008A
patent/HU205078B/en
not_active
IP Right Cessation

1990-05-11
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SU904743820A
patent/RU1839671C/en
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patent/DK0397281T3/en
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1990-05-11
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1990-05-11
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JP2122854A
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AT90201193T
patent/ATE144979T1/en
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HU913709A
patent/HU913709D0/en
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patent/ES2095854T3/en
not_active
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UA4743820A
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Patent Citations (3)

* Cited by examiner, † Cited by third party

Publication number
Priority date
Publication date
Assignee
Title

EP0030214A2
(en)

1979-11-30
1981-06-10
Ciba-Geigy Ag
Process for the preparation of 2,3,5,6-tetrachloropyridine and 3,5,6-trichloropyridin-2-ol

US4469896A
(en)

1981-08-17
1984-09-04
Ciba-Geigy Corporation
Process for the production of chloropyridines substituted by methyl, trichloromethyl or trifluoromethyl groups

EP0341585A1
(en)

1988-05-11
1989-11-15
Luxembourg Industries (Pamol) Ltd.
Production of 3,5,6-trichloro-pyridin-2-ol and novel intermediates thereof

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1990-12-20

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1991-01-11

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1992-02-28

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1996-07-15

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