http://rdf.ncbi.nlm.nih.gov/pubchem/patent/ES-356317-A1
Outgoing Links
| Predicate | Object |
|---|---|
| assignee | http://rdf.ncbi.nlm.nih.gov/pubchem/patentassignee/MD5_404c787d6b2e4d3f135ee391f79199a0 |
| classificationIPCInventive | http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07C- |
| filingDate | 1968-07-20-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| publicationDate | 1970-05-16-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| publicationNumber | ES-356317-A1 |
| titleOfInvention | PROCEDURE FOR THE PREPARATION OF SUBSTITUTED AMINOPHENYLACETIC ACIDS. |
| abstract | Process for the preparation of substituted aminophenylacetic acids and their derivatives of the formula I ** (See formula) ** where R1 and R2 are the same or different and mean H or alkyl with 1-4 carbon atoms R3 means F, Hal, CF3, OH, NO2, CN, R9, OR9, SH, SR9, NR1-COR9, NR1R2, SO2NR1R2, SOR9 or SO2R9, R4, R5 and R6 mean H, one of these radicals also means F, Hal, R9, OR9 or SR9, the radicals R4 and R5 also mean together a tetramethylene optionally containing 1-2 double bonds, R7 and R8 are the same or different and mean straight or branched alkyl with 1-7 carbon atoms or together they mean an alkylenic chain with 2-14 straight or branched carbon atoms, optionally interrupted by an oxygen or sulfur atom, R9 means alkyl with 1-4 carbon atoms, A means COOA1, CONA2A3, CONA4, C (= NOH) OH or C (OR9) 3, A1, A2 and A3 are the same or different and denote H, an alkyl or cycloalkyl group with in each case up to 12 carbon atoms branched and/or interrupted by Y and/or one to three times by O and/or optionally containing an NH2 group and/or an OH group and/or one to two CC, A5-NA4, phenyl or aralkyl multiple bonds with 6-14 carbon atoms in total, A4 means alkylene with up to 6 carbon atoms, optionally interrupted by O or Y, A5 means alkylene with 1-6 carbon atoms, Y means S, NH, N-alkyl with 1-6 carbon atoms, optionally substituted by OH, N-phenyl or N-phenylalkyl with 7-10 carbon atoms, wherein, in addition, in case R4 and R5 mean together a tetramethylene which optionally contains 1-2 double bonds, R3 can be H and simultaneously R6 can be H, F, Hal, CF3, OH, NO2, CN, R9, OR9, SR9, NR1COR9, NR1R2, SO2NR1R2, SOR9 or SO2R9, as well as its salts with acids or possibly bases, its quaternary ammonium salts and eventually its anhydrides, characterized in that a) in case it is desired to obtain carboxylic acids of the formula 1 (A = COOH), functional acid derivatives of such carboxylic acids, such as in particular amides, thioamides, thioesters, esters, hydrazides, acid halides, acids, anhydrides, iminoesters, amidines, hydroxamic acids, nitriles, trihalogenomethanes, imino acid halides, are saponified in neutral, acidic or alkaline medium or thermolytically decomposed, in particular torcial-alkyl esters, such as torcibutyl ester or b) compounds of the formula 2 are oxidized Z2-L 2 where L means an oxidizable group to form a carboxylic group, such as in particular -CHO, CH2OH, CH3, 1-alkenyl, 1-alkynyl, 1,2-dihydroxyalkyl or 1-oxoalkyl, or c) a diazoketone of formula 3 is transposed Z-CO-CR1 = N2 3 under the usual conditions of a Wolff rearrangement in the presence of A1OH, A2A3NH, A4NH or Nh2OH or d) a metal-organic compound of the formula 4 is reacted Z2-M 4 where M means metal, especially alkali metal, Cd-R9, Zn-R9 or Mg-Hal, with carbon dioxide or e) a halogenoketone of formula 5 is transposed Z-CO-CR1R2-Hal 5 under the usual conditions of a Faworski transposition or f) a compound of the formula 6 or 7 is reacted Z2-B1 6 Z-CHR2-B2 7 where B1 means OH, esterified OH, OM, Cl, Br, or J and B2 means alkyl with 1-4 carbon atoms substituted by B1, with carbon oxide, or g) a malonic acid derivative of the formula is decarboxylated ** (See formula) ** h) a beta-keto acid derivative of the formula 9 is subjected ** (See formula) ** where R10 means acyl or a hydrocarbon radical to an acid cleavage or i) a compound of the formula 1 is treated, wherein one or more groups and/or 6-0 multiple substitutable or reducible hydrogen bonds are present, as in particular the compounds of the formula 1 wherein R1 to R9 and A have the significance indicated at the beginning, but at least one of these radicals contains one or more halogen atoms, and/or one or more OH, SH, NH2 and/or OH, SH or NH2 substituted groups. by hydrocarbon radicals and/or one or more groups C = O and/or C = S and/or one or more double bonds C = N and/or C = C and/or triple bonds C ≡ C and/or where R1 and R2 together denote O or S or an alkyl group with 1-4 carbon atoms or where R1 means Hal, OH, SH, NH2 or OH, SH or NH2 substituted by hydrocarbon radicals, and/or wherein the benzene nucleus additionally carries 2,3,5 and/or 6 position, halogen atoms or diazonium salt groups and/or if R 4 and R 5 together represent a tetramethylene group optionally containing 1-2 doubles In addition, the linkages are additionally one or more halogen atoms and/or diazonium salt groups and/or where A is found, a benzylic ester or benzyl amide group or an ester or amide group of benzyl equivalent, which can be transformed hydrogenolytically into the carboxyl group or the -CONHA1 group, or a compound of the formula 10 R11-Z1 10 where R11 means B ⊖ R12 = NR ⊕ 13- OR ** (See formula) ** B ⊖ means anion of preference Hal, R12 means alkylidene with 1-7 carbon atoms Y R13 means alkyl with 1-7 carbon atoms, wherein the radicals R12 and/or R13 contain one or more C = C double bonds or triple C ≡ C bonds and these radicals may also be linked in ring form directly with each other or on an oxygen or sulfur atom, with hydrogen or catalytically activated hydrogen cessation agents or j) a compound of the formula 11 is reacted with a compound of the formula 12 or a compound of the formula 13 with a compound of the formula (See formula) R9X 12 (See formula) R9M 14 where X means a radical which can be doubled with M as MX, especially halogen, a radical of sulfuric acid or of sulfonic acid, or k) a compound of the formula 15 is reacted with a compound of the formula 16 or a compound of the formula 17 with a compound of the formula Z - X 15 M-CR1R2-A 16 Z - Q 17 X-CR1R2-A 18 where Q means H or M, possibly in the presence of a Friedel-Crafts catalyst or l) a compound of formula 19 is reacted with an amine of formula 20 or an amine of formula 21, 22 or 23 with a compound of formula 24 or under N-alkylating conditions, wherein the compounds 24 and 25 can also represent together a single compound in the reaction with a compound of the formula 21 according to the significance indicated at the beginning for R7 and R8 X1-Z1 19 R7R8NH 20 NH2-Z1 21 R7-NH-Z1 22 R8NH-Z1 23 R7-X1 24 R8-X1 25 where R3 in compound 19 advantageously means an electron-withdrawing group, such as NO2, CN, SO2NR1R2, NR1-COR9 or CF3 and X1 means a radical substituted by an amino group, such as in particular halogen, OH, acyloxy, a secondary or tertiary amino group, a radical of sulfuric acid, of alkylsulfuric acid or of sulfonic acid, and both radicals X1 of compounds 24 and 25 in the reaction with the amine 21 can also mean together an oxygen or sulfur atom, or m) an amino compound of the formula 2l is reacted with one or two olefins with 2-7 carbon atoms, rectilinear or branched, the same or different, or with an alkdiene with 4-14 carbon atoms straight or branched, whose chain it may also be interrupted by an oxygen or sulfur atom, or amino compounds of the formula 22 or 23 are reacted with a rectilinear or branched olefin with 2-7 carbon atoms, which may also be linked to the radicals R7 or either R8 directly or on a hetero atom, such as O, S, or n) a compound of the formula 26 is reacted H-Z1 with an amine of formula 27 R7R8N-Hal 27 in the presence of Friedel-Crafts catalysts, or o) in a compound of formula 1, which contains R 3 instead (or, in the case where R 3 signifies H, as well as simultaneously R 4 and R 5 together signify a tetramethylene group which optionally contains 1-2 double bonds, instead of R6) hydrogen, the substituent R3 (or R6) is introduced, that is, if R3 (or R6) means chlorine, bromine or iodine, by halogenation, in particular by reaction with elemental halogen, advantageously low, addition of catalysts, such as iron-III, aluminum, antimony-III halides, tin-IV halides, with hypohalogenic acids, tert.butyl hypohalogenites, compounds of different halogens among themselves, such as ClJ, ClBr, BrJ, SO2-halogens, advantageously under the addition of peracids, and N-halogenocarboxylic acid amides, as well as N-halogenocarboxylic acid imides or, if R3 (or R6) means iodine, by iodination, especially also by reaction of the compound 3- (or 6-) Hg-acetate with iodine or if R3 (or R6) means NO2, by nitration, especially by reaction with nitric oxide, nitronium salts, advantageously under the addition of Friedel-Crafts catalysts, HNO3, optionally in mixture with acetic acid, acetic anhydride, H2SO4, pyrosulfuric acid, fuming sulfuric acid, H2SeO4, HClO4-, with acyl nitrates, such as acetyl or benzoyl nitrate, with nitric acid esters, such as nitrate, with nitrosulfonic acid, nitrosylsulfuric acid, nitroguanidine, with metal nitrates (such as Cu, Fe, Mn, Co, Ni nitrates) mixed with acetic anhydride or glacial acetic acid or, if R3 (or R6) means R9, SR9, SOR9, SO2R9 or NR1R2, in particular by reaction with R9X2 or olefins with up to 4 carbon atoms or by reaction with R9SX2, R9SOX2, R9SO2X2 or R1R2N-X2 in the presence of Lewis acids, in particular Friedel-Crafts catalysts, optionally under HX2 splitting conditions, where X 2 is Hal, OH, acyloxy or alkoxy with preferably up to 4 carbon atoms, a radical of sulfuric acid or of sulfonic acid, or p) in a compound of formula 1, wherein R3 means NH2, the NH2 group is exchanged after transformation into a diazonium salt by halogen, NO2, CN, R9S, R9O or OH, or where R3 stands for CONH2, the CONH2 group is transformed by dehydrating agents, such as in particular P2O5, POCl3, PCl5 or SOCl2, in a CN group, or where R3 means NO2 or instead of R3, it is JO or JO2, the NO2 group is reduced to form NH2 or the JO or JO2 group is reduced to form iodine, or where instead of R3 is NH-NH2 or NHNH2 substituted by hydrocarbon radicals, this grouping of hydrazine is replaced by bromine or iodine, or where R3 means Hal, Hal is exchanged for NR1R2, or where instead of R3 is one of the radicals OM1, SM1, N (M1) 2 or S02N (M1) 2 and M1 means H or metal, especially alkali metal or alkaline earth metal, these substituents which are found in place of R3 are reacted with olefins with 2-4 carbon atoms, diazoalkanes with 1-4 carbon atoms or with compounds R9X1, optionally under M1X1 cleaving conditions, or where R3 stands for NH-R1 the NH-R1 group by treatment with ketenas with up to 5 carbon atoms or with carboxylic acid derivatives suitable for acylation reactions, such as esters, anhydrides, carboxylic acid halides, which are derived from carboxylic acids with up to 5 carbon atoms for forming the group NR1-COR9 or this amide group is released hydrolytically into one of its functional derivatives, or where R3 means SR9 or instead of R3 it is NO, the SR9 group is oxidized to form the group SOR9 or SO2R9 or the nitrous group is oxidized to form the nitro group or where instead of R3 is a sulphonic acid radical, in particular a sulfonic acid halide, a sulfonic acid ester or a sulfonic acid anhydride, These sulphonic acid derivatives are reacted with an amine of the formula R1R2NH 28 or in a compound of formula 1 (wherein R3 means H as well as simultaneously R4 and R5 together represent a tetramethylene group optionally containing 1-2 double bonds) wherein instead of Rg the substituents indicated above for R3 are present, this substituent is transformed in an analogous way, or q) in a compound of formula 1, where two of the radicals R4, R5 and R6 mean H and the third of these radicals means H or NH2, OH or SH is in place the atom H that is in place of this third radical or the group that is in place of this third radical is replaced analogously to the procedure o) or p) by one of the radicals F, Hal, R9, OR9 or SR9, or r) compounds of formula 1, where R7 and R8 are the same or different and mean alkyl with 1-7 carbon atoms substituted by OM1 or SM1, one of the substituents OM1 or SM1 can also be substituted by X1, it is reacted under H 2 O or H 2 X 1 splitting conditions to form compounds containing the O ring or the S ring or s) compounds of the formula 29 are decarboxylated Z2-CO-COOH 29 or t) compounds of the formula 30 ** (See formula) ** they are treated with catalytically activated hydrogen or hydrogen cessation agents or are reacted with a compound of the formula 14 (R9M) or u) a compound of formula 1, wherein instead of A is COOM1, COOR14, COOacyl, COHal, it is optionally reacted with a compound of the formula 31 or with an olefin derived from 31 by formal cleavage of H2O or either with an epoxide derivative of 31 by formal dehydrogenation or with compound of the formula 32 to 36 or with my ethyleneimine derivative of 33 by formal dehydrogenation or with diazomethane, diazoethane, phenyldiazomethane or hydroxylamine A1OH 31 A1Oacyl 32 A2A3NH 33 A4NH 34 A2-N = C = O 35 A1-X 36 where R 14 is an optionally substituted hydrocarbon radical, preferably alkyl, with 1-4 carbon atoms, or v) compounds of the formula 1 are hydrolysed, wherein instead of A is (see formula) where E means = NR15, = S, = NOR15 or N-NR15R16, R15 and R16 are the same or different and denote H or an optionally substituted hydrocarbon radical (preferably alkyl with 1-4 carbon atoms or phenyl), to form carboxylic acids, Esters or amides of the formula 1, or w) to compounds of formula 1, wherein instead of A is CN, H2O is added under formation of amides of formula 1, or x) compounds of the formula 37 are subjected to the reaction of Willgerodt or compounds of the formula 38, in particular under the addition of acidic catalysts, to a transposition in the presence of the amines 33 or 34, in particular under the addition of the polysulfides. of Beckmann or compounds of the formula 39 by reaction with HN3 to a Schmidt decomposition Z-CO-CH3 37 Z2-CA1 = NOH 38 Z2-CO-A1 39 or y) an aldehyde of the formula 40 is reacted Z2-CHO 40 with nitrohydroxylaminic acid or benzenesulfonylhydroxylamine, especially in alkaline solution, or an aldoxime of an aldehyde of the formula 40, especially with H2O2 or peracids, is oxidized to form a hydroxamic acid of the formula 1 or z) compounds of the formula 1 are reacted, wherein instead of A there is the group C (= NR15) OR14 present advantageously as a salt, with alcohols of the formula 41 or compounds of the formula 42 with esters of orthocarbonic acid of the formula 43 R9OH 41 Z2-M 42 C (OR9) 4 43 to form orthoesters of formula 1 or za) compounds of the formula 44 are reacted with compounds of the formula 45 or compounds of the formula 46 with compounds of the formula 47 or compounds of the formula 48 with compounds of the formula Z2-D-A6-X3 44, M1-Y-A7 45 Z2-D-A6-YM1 46 X3A7 47 Z2-D-A5-X3 48 MNA4 49 under M1X1 splitting conditions or from compounds of the formulas 50 to 54 ** (See formula) ** where D means COO or CONA2, X3 means OH, SH, Oacilo, Sacilo or X, A6-Y-A7 and A8Y adopt the significance of A1 and A9-Y-A10 adopt the meaning of A4, unfolds M1X3 or zb) a compound corresponding to formula 1 is treated, wherein instead of at least one double bond of the benzene nucleus or (if R4 and R5 mean together a tetramethylene containing optionally 1-2 double bonds) of the naphthalene nucleus is present a saturated CC bond, with dehydrogenating agents, as in particular dehydrogenation catalysts or oxides of metal, chloranil, sulfur, selenium or alkyl disulfides, or zc) a compound corresponding to formula 1 is cyclized, where instead of R4 and R5 the radicals H and R17 are found and where R17 means a group - (CH2) 4-X2 optionally containing a group - (CH2) 3-CHX4X5 containing an additional double bond or optionally one or two additional double bonds, a 3-butenyl, 3-butynyl group, 1, 3-butadienyl or 1-buten-3-ynyl, X4 and X5 are the same or different and mean OR15, SR15, NR15R16 or mean together O or E, in particular in the presence of Lewis acids and/or acids, as Friedel-Crafte catalysts, or optionally with dehydrating agents, such as P2P5, POCl3, PCl5, or COCl2 or optionally under other unfolding conditions of HX4, HX5 or HX2 or zd) in a compound corresponding to formula 1, wherein instead of the radicals R and R there is a tetramethylene substituted once by X6, and optionally containing a double bond, or substituted twice by X6', where X6 means a radical split with H as HX6, in particular Hal or OH, SH or NH2 optionally substituted by alkyl, acyl, alkylsulfonyl or alkoxysulfonyl with preferably up to 4 carbon atoms, the X6 substituent (s) is deleted as HX6 under the formation of one or two double bonds or ze) in a compound corresponding to formula 1, wherein instead of the radicals R4 and R5 is a tetramethylene containing a double bond, optionally doubled by X7 and X8 in position 1,2 or 1,4 or 3, 4, and where X7 and X8 are the same or different and denote Hal or OH optionally substituted by alkyl, acyl, alkylsulfonyl or alkoxysulfonyl with preferably up to 4 carbon atoms in each case, the two substituents X7 and X8 are eliminated in each case under the formation of a double bond, especially with metals, such as Zn, Zn-Cu, Na or Li, or with metalorganic compounds, such as Grignard compounds or lithium organics, and/or zf) a compound of the formula 1 is optionally converted into its physiologically tolerable salts with acids or bases or quaternary ammonium salts and/or its unfolding derivatives under physiological conditions, in particular its anhydrides, and optionally mixtures of racemates from the Formula 1 in the unit racemates and the optionally present racemates of the formula 1 are separated in a manner known per se from their optical antipodes and/or the compounds of the formula 1 are liberated from their salts with acids or bases. (Machine-translation by Google Translate, not legally binding) |
| priorityDate | 1967-07-22-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| type | http://data.epo.org/linked-data/def/patent/Publication |
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Total number of triples: 116.