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WO1995030764A1 - Production et deshydratation de diphenylacetylenes hydroxyles - Google Patents

Production et deshydratation de diphenylacetylenes hydroxyles Download PDF

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Publication number
WO1995030764A1
WO1995030764A1 PCT/US1995/001958 US9501958W WO9530764A1 WO 1995030764 A1 WO1995030764 A1 WO 1995030764A1 US 9501958 W US9501958 W US 9501958W WO 9530764 A1 WO9530764 A1 WO 9530764A1
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WIPO (PCT)
Prior art keywords
formula
compound
cis
dihydrodiol
hydroxy
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US1995/001958
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English (en)
Inventor
Alan Douglas Grund
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
BIO-TECHNICAL RESOURCES LP
Original Assignee
BIO-TECHNICAL RESOURCES LP
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from US08/240,125 external-priority patent/US5420361A/en
Application filed by BIO-TECHNICAL RESOURCES LP filed Critical BIO-TECHNICAL RESOURCES LP
Priority to AU18453/95A priority Critical patent/AU1845395A/en
Publication of WO1995030764A1 publication Critical patent/WO1995030764A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C35/00—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a ring other than a six-membered aromatic ring
    • C07C35/21—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a ring other than a six-membered aromatic ring polycyclic, at least one hydroxy group bound to a non-condensed ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
    • C07C37/06—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by conversion of non-aromatic six-membered rings or of such rings formed in situ into aromatic six-membered rings, e.g. by dehydrogenation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C39/00—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring
    • C07C39/205—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring polycyclic, containing only six-membered aromatic rings as cyclic parts with unsaturation outside the rings
    • C07C39/21—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring polycyclic, containing only six-membered aromatic rings as cyclic parts with unsaturation outside the rings with at least one hydroxy group on a non-condensed ring
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P7/00—Preparation of oxygen-containing organic compounds
    • C12P7/02—Preparation of oxygen-containing organic compounds containing a hydroxy group
    • C12P7/22—Preparation of oxygen-containing organic compounds containing a hydroxy group aromatic

Definitions

  • the present invention relates to the production of the cis dihydrodiol derivative of diphenyl acetylenes and the dehydration thereof to form the corresponding meta-substituted phenol derivative.
  • X and Y may be the same or different, and represent hydrogen, halogen, ceryl, or cyano groups except that X and Y cannot both be hydrogen, using strains ofPseudomonasputida.
  • U. S. Patent No. 4,532,209 discloses the production of p-cresol by the acidification of an aqueous solution of 4-methylcyclohexa-3,5-diene-l,2-diol-l- carboxylic acid.
  • (+)-cis-2,3-dihydroxy-l-methylcyclohexa-4,6-diene is disclosed by D.T. Gibson et al., Biochemistry, pp. 1626-1630, Vol. 9, (1970) along with the acid catalyzed dehydration of (+)-cis-2,3-dihydroxy-l-methylcyclohexa -4,6-diene.
  • U.K. Patent No. 2,203,150 B discloses preparing fluorophenols by dehydrating l,2-dihydroxy-3-fluorocyclohexa-3,5-diene in the presence of base and subsequently recovering 2 and/or 3-fluorophenol. The use of base does not make the reaction overly selective for 3-fluorophenol.
  • R 3 is selected from the group consisting of hydroxy, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, hydroxy substituted cycloalkyl, hydroxy substituted phenyl, hydroxy substituted phenalkyl, amino substituted alkyl and alkyl substituted by the group alkyl
  • R 4 is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, phenyl, phenalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxy cycloalkyl, hydroxyalkenyl, hydroxy cycloalkyl, hydroxy substituted phenyl, hydroxy substituted phenalkyl, amino alkyl and alkyl substituted by the group alkyl.
  • n and o are individually 1 or 0 with the proviso that both m and o may not be 0, n is 0, 1 or 2; and X is phenyl, divalent oxygen, sulfur, sulfinyl, sulfonyl, carbonyl, amino or alkylamino or X is a divalent alkylene, alkenylene or alkynylene chain which may optionally include one or more divalent oxygen, sulfur, sulfinyl, sulfonyl, carbonyl, amino or alkylamino moieties in any combination by enzymatically biotransforming the corresponding biphenyl compound with a microorganism.
  • U.S. 4,772,755 discloses compounds of the formula wherein X is hydroxy, alkoxy or alkanoyloxy, Ar 1 is an organic group such as phenyl which may be independently substituted by one or more of alkyl, alkoxy, alkylthio, dialkylamino, halogen etc. and R is an unsubstituted or substituted alkyl group.
  • EP 400,779 Al discloses production of meta-hydroxypheny-acetylenes from phenyl substituted ketal or acetal precursors.
  • the present invention relates to the preparation of 3-hydroxy- diphenylacetylene or less preferably 2-hydroxydiphenylacetylene.
  • the first step in the process is the preparation of diphenylacetylene dihydrodiol by the microbial oxidation of diphenylacetylene.
  • the diphenylacetylene dihydrodiol is then dehydrated with a base at an elevated temperature to produce 3-hydroxy- diphenylacetylene.
  • the diphenylacetylene dihydrodiol can be dehydrated with an acid to produce 2-hydroxydiphenylacetylene.
  • the first aspect of the present involves the production of diphenylacetylene dihydrodiol from diphenylacetylene. This is done by microbial oxidation using a suitable bacteria.
  • a bacterium is isolated by enrichment technique from the environment or obtained from a depository.
  • the first criteria for the bacterium is that it is capable of growth on biphenyl as the sole carbon and energy source.
  • suitable bacteria are of the genus Pseudomonas and, more specifically, are mutants of Pseudomonas Strain 73.
  • Strain 73 is a mobile, anaerobic bacterium having a rod morphology (1 x 3 microns).
  • the organism is negative for the production of pigments, accumulation of poly- ⁇ -hydroxybutyrate (PHB), hydrolysis of gelatin, or formation of nitrogen from nitrate.
  • PHB poly- ⁇ -hydroxybutyrate
  • the organism has no requirement for specific growth factors and does not grow at 41°C.
  • the starting strain is then treated with N-methyl-N'-nitro-N- nitrosoquanidine or ultraviolet light in the known manner to effect mutagenesis to obtain mutants which are unable to grow on biphenyl. Certain of these mutants will be found which lack a functional dihydrodiol dehydrogenase.
  • UV absorbance maximum 321 nm.
  • This UV absorbing metabolite is the cis-2,3-dihydrodiol of diphenyl acetylene, and can accumulate in the growth medium at concentrations of from 100 parts per million (ppm) to 1,000 pp or even higher, depending on growth conditions. This dihydrodiol can then be dehydrated either to the 2 or 3-hydroxydiphenyl acetylene phenol as described below.
  • ATCC strain number 55272 is a Pseudomonas Strain 73-4, a mutant of
  • Pseudomonas Strain 73 described above. This mutant possesses all of the characteristics of a Pseudomonas Strain 73, with the exception that the bacterium is incapable of growth on biphenyl and that it lacks the diol dehydrogenase activity which converts aromatic cis-dihydrodiols to catechols.
  • the strain was received by the American Type Culture Collection, 12301
  • a cell free aqueous broth containing the cis-2,3- diol of diphenylacetylene at a concentration of 100 to 5,000 ppm is used.
  • the broth is quickly heated to 50° to 120°C, preferably from 75° to 100°C.
  • a solution of base at the elevated temperature is quickly added and mixed.
  • the final concentration of base is at least 0.1N, preferably 1.0N or higher up to 8.0N.
  • the solution is held at the elevated temperature for at least 15 minutes, preferably for longer times of 1 to 10 hours.
  • the mixture is then cooled to 20° to 30°C and the phenols recovered such as by extraction with organic solvents.
  • the preferred bases are sodium hydroxide, potassium hydroxide and cesium hydroxide, with sodium hydroxide preferred because of cost.
  • the conversion to the 3-hydroxydiphenylacetylene isomer is 100% when the process is operated under optimum conditions.
  • the compounds produced by the present invention are useful as intermediates for producing polymeric materials.
  • reaction schemes I, II or III Generally the reactions of the present invention can be represented by the following reaction schemes I, II or III.
  • the composition of the minimal salts (MS) medium used in the following Example 1 in grams per liter was as follows: NH-jCl, 1.0; NaNO 3 , 1.0; MgSO 4 , 0.16; FeSO 4 .7H 2 O, 0.004; K 2 HPO 4 , 4.4; KH 2 PO 4 , 3.4; trace salts (TS) solution, 2 ml; and distilled water, 1 liter.
  • the pH of the medium was adjusted to 7.0 using HCl as required.
  • the trace salts solution consisted in grams per liter: concentrated HCl, 10ml; CuSO 4 .5H 2 O, 0.063; CoCl 2 .6H 2 O, 0.16; H 3 BO 3 , 0.91; ZnSO .7H 2 O, 1.8; MnSO 4 .H 2 O, 1.2; NaMoO 4 .2H 2 O, 0.048; CaCl 2 .2H 2 O, 11.4, VSO 4 .2H 2 O, 0.08, Ni(NO 3 ) 2 .6H 2 O, 0.04; Na 2 SeO 3 , 0.04; and distilled water, 980 ml. Carbon sources were added from sterile stock solutions to autoclaved media (1% final concentration).
  • Pseudomonas strain 73-4 ATCC 55272, a mutant of Pseudomonas strain 73, lacking a functional diol dehydrogenase, was grown in the MS medium described above plus 1% succinic acid as carbon source.
  • the organism was grown in 100 ml of medium in a 500 ml shake flask agitated at 150 RPM at 30°C.
  • Diphenylacetylene was provided as solid crystals added to the growth medium. After 16 hours incubation the cells were removed by centrifugation and the broth assayed for the diol of diphenylacetylene by gas chromatography. The compound was present at 320 ppm.
  • Pseudomonas strain 73-4 was grown in the MS medium as described in Example 1, but with glucose as the sole carbon and energy source. Exposure to diphenylacetylene for 16 hours resulted in formation of diphenylacetylene- cis-2,3-dihydrodiol at a concentration of 125 ppm.
  • Diphenylacetylene dihydrodiol was produced to a concentration of 150 ppm using a microorganism isolated from the environment and a process similar to that described in Example 1. Following removal of the cells by centrifiigation, the crude broth containing the dihydrodiol was divided into four portions and treated as described in the Table below.

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  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

L'invention se rapporte à la production de composés cis-dihydrodiol de la formule (1) dans laquelle n vaut 0 ou 1 (de préférence 0), production réalisée par l'oxydation microbienne d'un composé de la formule (2) mettant en ÷uvre un mutant d'une bactérie Pseudomonas à une température comprise entre 25 °C et 35 °C et à un pH compris entre 6 et 8. Un traitement ultérieur du composé cis-dihydrodiol avec une solution basique, aqueuse permettra d'obtenir le 3-dihydrodiphénylacétylène correspondant, et un autre traitement du composé cis-dihydrodiol avec une solution acide aqueuse permettra d'obtenir l'acétylène 2-hydroxy correspondant.
PCT/US1995/001958 1994-05-10 1995-02-15 Production et deshydratation de diphenylacetylenes hydroxyles Ceased WO1995030764A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU18453/95A AU1845395A (en) 1994-05-10 1995-02-15 Formation of and dehydraton of hydroxylated diphenylacetylenes

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US08/240,125 1994-05-10
US08/240,125 US5420361A (en) 1992-02-05 1994-05-10 Formulation of and dehydration of hydroxylated diphenyl acetylenes
US08/286,900 1994-08-08
US08/286,900 US5470728A (en) 1992-02-05 1994-08-08 Formation of and dehydration of hydroxylated diphenyl acetylenes using Pseudomonas ATCC 55272

Publications (1)

Publication Number Publication Date
WO1995030764A1 true WO1995030764A1 (fr) 1995-11-16

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PCT/US1995/001958 Ceased WO1995030764A1 (fr) 1994-05-10 1995-02-15 Production et deshydratation de diphenylacetylenes hydroxyles

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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4153509A (en) * 1977-10-17 1979-05-08 Union Carbide Corporation Microbial production of hydroxylated biphenyl compounds
US4508822A (en) * 1981-10-06 1985-04-02 Imperial Chemical Industries, Plc Biochemical process
US4652584A (en) * 1984-07-13 1987-03-24 Mcneilab, Inc. Acetylenic phenoxypropanol derivatives and pharmaceutical compositions for the treatment of hypertension
GB2203150A (en) * 1987-04-09 1988-10-12 Shell Int Research Preparation of fluorophenols
EP0400779A1 (fr) * 1989-05-31 1990-12-05 Minnesota Mining And Manufacturing Company Préparation biologique de diols de cyclohexadiène
US5093514A (en) * 1990-12-07 1992-03-03 E. I. Du Pont De Nemours And Company Base-catalyzed dehydration of substituted cis-1,2-dihydroxycyclohexa-3,5-dienes

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4153509A (en) * 1977-10-17 1979-05-08 Union Carbide Corporation Microbial production of hydroxylated biphenyl compounds
US4508822A (en) * 1981-10-06 1985-04-02 Imperial Chemical Industries, Plc Biochemical process
US4652584A (en) * 1984-07-13 1987-03-24 Mcneilab, Inc. Acetylenic phenoxypropanol derivatives and pharmaceutical compositions for the treatment of hypertension
GB2203150A (en) * 1987-04-09 1988-10-12 Shell Int Research Preparation of fluorophenols
EP0400779A1 (fr) * 1989-05-31 1990-12-05 Minnesota Mining And Manufacturing Company Préparation biologique de diols de cyclohexadiène
US5093514A (en) * 1990-12-07 1992-03-03 E. I. Du Pont De Nemours And Company Base-catalyzed dehydration of substituted cis-1,2-dihydroxycyclohexa-3,5-dienes

Non-Patent Citations (11)

* Cited by examiner, † Cited by third party
Title
1963, 21(4), 243-248, BOLL. SCI. FAC. CHIM. IND. BOLOGNA *
C.H. CUMMINS: "Synthesis of symmetrical diarylalkynes by double Still coupling of bis(tributylstannyl)acetylene", TETRAHEDRON LETTERS, vol. 35, no. 6, 7 February 1994 (1994-02-07), OXFORD, GB, pages 857 - 860 *
CHEMICAL ABSTRACTS, vol. 60, no. 13, 22 June 1964, Columbus, Ohio, US; abstract no. 15808e, A.S. ANGELONI, ET AL.:: "Electrophilic substitutions in the benzofuran series: bromination and acetylation of 2-phenylbenzofuran" *
D.T. GIBSON, ET AL.:: "Formation of (+)-cis-dihydroxy-1-methylcyclohexa-4,6- diene from toluene by Psedomonas putida", BIOCHEMISTRY, vol. 9, no. 7, 31 March 1970 (1970-03-31), WASHINGTON, DC, US, pages 1626 - 1630 *
D.T. GIBSON, ET AL.:: "Initial reactions in the oxidation of ethylbenzene by Pseudomonas putida", BIOCHEMISTRY, vol. 12, no. 8, 10 April 1973 (1973-04-10), WASHINGTON, DC, US, pages 1520 - 1527 *
J. CHATT, ET AL.:: "Complexes of acetylenes with platinum(II). Part II. Hydroxy- and methoxyalkylacetylenes", JOURNAL OF THE CHEMICAL SOCIETY, no. 11, LETCHWORTH, GB, pages 5170 - 5183 *
L.-S. TAN, ET AL.:: "Benzocyclobutene in polymer synthesis. II. Solid state Diels-Alder polymerisation utilising an in situ generated diene and an alkyne", JOURNAL OF POLYMER CHEMISTRY: PART A: POLYMER CHEMISTRY, vol. 25, no. 11, NEW YORK, US, pages 3159 - 3172 *
R.L. LESINGER, ET AL.:: "Organoboron compounds. XIII. Boronic acids with neighbouring unsaturated groups", JOURNAL OF ORGANIC CHEMISTRY, vol. 26, no. 4, 18 April 1961 (1961-04-18), WASHINGTON, DC, US, pages 1271 - 1273 *
S. JAYARAMAN, ET AL.:: "Synthesis of 3-phenylethylnylphenol", POLYMER PREPRINTS, vol. 34, no. 1, 5 March 1993 (1993-03-05), NEW YORK, NY, US, pages 511 - 512 *
T. HUDLICKY, ET AL.:: "Palladium-catalysed coupling of terminal alkynes to the free cis-diol metabolite produced from the oxidation of bromobenzene by Pseudomonas putida: synthesis of new homochiral 3-alkynyl cis-cyclohexa-3,5-diene- 1,2-diols", TETRAHEDRON: ASYMMETRY, vol. 3, no. 2, OXFORD, GB, pages 217 - 220 *
Y. KONDO, ET AL.:: "Palladium-catalysed indole and benzofuran ring formation accompanying carbonylation", HETEROCYCLES, vol. 29, no. 5, AMSTERDAM, NL, pages 1013 - 1016 *

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