DE1643458C3 - N- (2-alkoxybenzoyl) -p-aminobenzoic acid aminoalkyl esters and their quaternary methylammonium derivatives and processes for their preparation - Google Patents
N- (2-alkoxybenzoyl) -p-aminobenzoic acid aminoalkyl esters and their quaternary methylammonium derivatives and processes for their preparationInfo
- Publication number
- DE1643458C3 DE1643458C3 DE19671643458 DE1643458A DE1643458C3 DE 1643458 C3 DE1643458 C3 DE 1643458C3 DE 19671643458 DE19671643458 DE 19671643458 DE 1643458 A DE1643458 A DE 1643458A DE 1643458 C3 DE1643458 C3 DE 1643458C3
- Authority
- DE
- Germany
- Prior art keywords
- aminobenzoic acid
- ethyl ester
- alkoxybenzoyl
- methyl
- acid
- 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.)
- Expired
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/14—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/12—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by halogen atoms or by nitro or nitroso groups
-
- E—FIXED CONSTRUCTIONS
- E05—LOCKS; KEYS; WINDOW OR DOOR FITTINGS; SAFES
- E05B—LOCKS; ACCESSORIES THEREFOR; HANDCUFFS
- E05B65/00—Locks or fastenings for special use
Description
R3 R 3
in der R n-C,- bis C1 ,-Alkyl. R1 Wasserstoff oder Chlor, Y Äthylen oder Propylen und R2 oder R3 jeweils Methyl oder Äthyl bedeuten oderzusammen den Piperidinring biiden, sowie deren quartäre Methylammoniumdenvate.in the R nC, - to C 1 , -alkyl. R 1 is hydrogen or chlorine, Y is ethylene or propylene and R 2 or R 3 is each methyl or ethyl or together form the piperidine ring, as well as their quaternary methylammonium derivatives.
2. N-P-in-OctyloxyJ-benzoylJ-p-aminobenzoesäure-(/?-diäthyl-methyl-ammonium)-älhylestcrbromid bzw. -jodid.2. N-P-yn-octyloxy-benzoyl-p-aminobenzoic acid - (/? - diethyl-methyl-ammonium) -ethyl ester bromide or iodide.
3. Verfahren zur Herstellung der Verbindungen nach Anspruch 1 oder 2, dadurch gekennzeichnet, daß man in an sich bekannter Weise ein gegebenenfalls in 5-SteIlung durch Chlor substituiertes 2-AIkoxybenzoylchlorid mit einem entsprechenden p-Aminobenzoesäuredialkylaminoalkylesler oder die entsprechende N-(2-Alkoxybenzoyl)-p-aminobenzoesäure mit dem Dialkylaminoalkylchlorid. oder das N-(2-Alkoxybenzoyl)-p-aminobenzoylchlorid bzw. einen N-(2-AlkoxybenzoyI)-p-aminobenzoesäurcester mit dem Dialkylaminoalkohol umsetzt, sowie gegebenenfalls mit entsprechenden Methylierungsmitteln wie üblich quaternierl.3. Process for the preparation of the compounds according to claim 1 or 2, characterized in that that, in a manner known per se, a 2-alkoxybenzoyl chloride which is optionally substituted in the 5-position by chlorine with a corresponding p-Aminobenzoesäuredialkylaminoalkylesler or the corresponding N- (2-alkoxybenzoyl) -p-aminobenzoic acid with the dialkylaminoalkyl chloride. or the N- (2-alkoxybenzoyl) -p-aminobenzoyl chloride or an N- (2-alkoxybenzoyl) -p-aminobenzoic acid ester with the dialkylamino alcohol, and optionally with the corresponding Methylating agents as usual quaternierl.
4040
Die Erfindung betrifft die in den Ansprüchen fr gelegten Verbindungen und Verfahren zu deren Herstellung. Die quartären Salze entsprechen der folgenden Strukturformel:The invention relates to what is set out in the claims Compounds and processes for their preparation. The quaternary salts correspond to the following Structural formula:
COO Y-NCOO Y-N
CH,CH,
R3 R 3
5555
in der X Bromid, Chlorid. .Iodid oder Sulfat bedeutet. Solche Verbindungen sind /.. U.:in the X bromide, chloride. .Means iodide or sulfate. Such connections are / .. U .:
6060
1. N-(2-Mcthoxybenzoyl)-p-aminobenzocsäure-(/fdiäthylamino)-äthylester (R = CH,; R' = H ; Y = (CH2),; R2 = R3 = C,H5); Schmp.: 57 bis 590 c·.. 1. N- (2-methoxybenzoyl) -p-aminobenzocic acid (/ fdiethylamino) -ethyl ester (R = CH ,; R '= H; Y = (CH 2 ) ,; R 2 = R 3 = C, H 5 ) ; Melting point: 57 to 590 c ..
2. N-(2-Äthoxybenzoyl)-p-aminobcn7.ocsäurc-(/J(-2. N- (2-Ethoxybenzoyl) -p-aminobcn7.ocsäurc - (/ J (-
diäthylamino)-älhylester (R = C2H5; R'=H; Y=(CH2)2; R2= R3 = C,H5); Schmp.: 94 bis 96° C.diethylamino) ethyl ester (R = C 2 H 5 ; R '= H; Y = (CH 2 ) 2 ; R 2 = R 3 = C, H 5 ); M.p .: 94 to 96 ° C.
N-(2-Äthoxybenzoyl)-p-aminobenzoesäure-(amethvl-/J-dimethylamino)-äthylester (R = C2H,-N- (2-Ethoxybenzoyl) -p-aminobenzoic acid (amethyl- / J-dimethylamino) ethyl ester (R = C 2 H, -
R' = HrY = CH3-eH-CH2;R2 = R3 = CH3): Schmp.: 106 bis 1090C. R '= hry = CH 3 -EH-CH 2; R 2 = R 3 = CH 3): m.p .: 106 to 109 0 C.
N-(2-Äthoxybenzoyl)-p-aminobenzoesäure-(ßpiperidino)-äthylester (R = C2H5; R1= H; Y=(CH,),; R2 = R3 = C5H1O); Schmp.: 135 bis 13-7°CN- (2-Ethoxybenzoyl) -p-aminobenzoic acid (β-piperidino) -ethyl ester (R = C 2 H 5 ; R 1 = H; Y = (CH,); R 2 = R 3 = C 5 H 1O ); M.p .: 135 to 13-7 ° C
js].[2-(n-Butoxy)-benzoyl]-p-aminobev: .säure-(/}-diäthylamino)-äthylester (R= n-C4Hq; R1 = H; Y = (CH,)2; R2 = R3 = C2H5); Schmp.: 81 bis 82° C.js]. [2- (n-Butoxy) -benzoyl] -p-aminobev :. acid - (/} - diethylamino) ethyl ester (R = nC 4 H q ; R 1 = H; Y = (CH,) 2 ; R 2 = R 3 = C 2 H 5 ); M.p .: 81 to 82 ° C.
6. N-[2-(n-Amyloxy)-benzoyl]-p-aminobenzoesäure-(ß-diäthylamino)-äthylester (R = n-C5Hn; R1 = H; Y = (CH2),; R2 = R3 = C2H5); Schmp.: 70 bis 72° C.6. N- [2- (n-Amyloxy) benzoyl] p-aminobenzoic acid (β-diethylamino) ethyl ester (R = nC 5 H n ; R 1 = H; Y = (CH 2 ); R 2 = R 3 = C 2 H 5 ); M.p .: 70 to 72 ° C.
7. N-rXn-OctyloxyJ-benzoylJ-p-aminobenzoesäure-(/?-diäthyJamino)-ät hy tester (R = n-C8H,7; R1 = H; Y = (CH2),: R2 = R3 = C2H5); Schmp.: 41bis42nC.7. N-rXn-OctyloxyJ-benzoylJ-p-aminobenzoic acid - (/? - diethyJamino) -äthy tester (R = nC 8 H, 7 ; R 1 = H; Y = (CH 2 ),: R 2 = R 3 = C 2 H 5 ); M.p .: 41 to 42 n C.
8. N-[2-(n-Nonyloxy)-benzoyl]-p-aminobenzoesäure-(ß-diäthylamino)-äthylester (R = n-CqH „; R1 = H; Y = (CH2)2; R2 = R3 = C2H5); Schmp.: 127 bis 129°C (Hydrochlorid).8. N- [2- (n-Nonyloxy) benzoyl] p-aminobenzoic acid (β-diethylamino) ethyl ester (R = nC q H "; R 1 = H; Y = (CH 2 ) 2 ; R 2 = R 3 = C 2 H 5 ); M.p .: 127 to 129 ° C (hydrochloride).
9. N-[2-(n-Decyloxy)-benzoyl]-p-aminobenzoesäure-(i?-diäthylamino)-äthylester (R = n-C10H2l; R1 = H;Y = (CH2)2;R2 = R3 = C2Hs);Schmp.: 132 bis 134" C (Hydrochlorid).9. N- [2- (n-Decyloxy) benzoyl] p-aminobenzoic acid (i? -Diethylamino) ethyl ester (R = nC 10 H 2l ; R 1 = H; Y = (CH 2 ) 2 ; R 2 = R 3 = C 2 H s ); m.p .: 132 to 134 "C (hydrochloride).
10. N-[2-(n-Dodecyloxy)-benzoyl]-p-aminobenzoesäure-(^-diäthylamino)-äthylester (R = n-CUH25; R1 = H; Y = (CH2)2; R2 = R3 = C2Hs); Schmp.: 140 bis 142" C (Hydrochlorid).10. N- [2- (n-Dodecyloxy) -benzoyl] -p-aminobenzoic acid - (^ - diethylamino) -ethyl ester (R = nC U H 25 ; R 1 = H; Y = (CH 2 ) 2 ; R 2 = R 3 = C 2 H s ); M.p .: 140 to 142 "C (hydrochloride).
11. N-(2-Methoxy-5-chlorbenzoyl)-p-aminobenzocsäure-(/?-diäthy lamino)-äthylester (R=CH1; R1 =CI;Y =(CH2)2;R2 = RJ=C2Hs):Schmp.: 81 bis 82° C.11. N- (2-methoxy-5-chlorobenzoyl) -p-aminobenzocic acid (/? - diethylamino) ethyl ester (R = CH 1 ; R 1 = CI; Y = (CH 2 ) 2 ; R 2 = R J = C 2 H s ): m.p .: 81 to 82 ° C.
12. N-(2-Äthoxy-5-chlorbenzoyl)-p-aminobenzocsäure-(^-diäthylamino)-äthylester (R = CH5; R' = Cl: Y = (CH2)2; R2 = R3 = CH 5); Schmp.: 111 bis 113" C.12. N- (2-Ethoxy-5-chlorobenzoyl) -p-aminobenzoic acid - (^ - diethylamino) -ethyl ester (R = CH 5 ; R '= Cl: Y = (CH 2 ) 2 ; R 2 = R 3 = CH 5 ); M.p .: 111 to 113 "C.
13. N-P-in-ButoxyJ-S-chlorbcnzoylJ-p-aminobenzoesäurc-(/i-diäthylamino)-äthylester (R = n-C4H,; R1 = Cl; Y = (CH2),; R2 = R3 = CH5): Schmp.: 86 bis 87° C.13. NP-in-ButoxyJ-S-chlorobenzoylJ-p-aminobenzoic acid c - (/ i-diethylamino) ethyl ester (R = nC 4 H ,; R 1 = Cl; Y = (CH 2 ) ,; R 2 = R 3 = CH 5 ): m.p .: 86 to 87 ° C.
14. N-ß^n-AmyloxyVS-chlorbcnzoyll-p-aminobenzoesäure-(/?-diäthylamino)-äthylesler (R = H-C5H1,; R1= Cl; Y= (CH2J2; R2 = R3 = C2H,); Schmp.: 85 bis 86" C.14. N-ß ^ n-AmyloxyVS-chlorobenzoyl-p-aminobenzoic acid - (/? - diethylamino) -äthylenler (R = HC 5 H 1 ,; R 1 = Cl; Y = (CH 2 J 2 ; R 2 = R 3 = C 2 H,); m.p .: 85 to 86 "C.
15. N-P-Oi-OctyloxyH^-chlorbenzoylr-p-aminobenzocsäure-(J?-diathylamino)-äthylester (R = n-CgHl7; R1 = Cl; Y = (CH,)2; R2 = R3 = C2H5); Schmp.: 63 bis 64° C.15. NP-Oi-OctyloxyH ^ -chlorobenzoylr-p-aminobenzocic acid (J? -Diethylamino) ethyl ester (R = nC g H 17 ; R 1 = Cl; Y = (CH,) 2 ; R 2 = R 3 = C 2 H 5 ); M.p .: 63 to 64 ° C.
Entsprechende Salze sind z. B.:Corresponding salts are z. B .:
16. N-(2-Methoxybenzoyl)-p-aminobenzoesäure-(ß-diäthyl-methyl-ammonium)-äthylestcr-jodid 16. N- (2-Methoxybenzoyl) -p-aminobenzoic acid- (ß-diethyl-methyl-ammonium) -äthylestcr-iodid
2 32 3
X = J); Schmp.: 198 bis 200"C.X = J); M.p .: 198 to 200 "C.
17. N-(2-Äthoxybcnzoyl)-aminobcnzoesäure-(//-mcthyldiälhyl-methyl-arnmonium)-äthylcsier-jodid (R =CH5:R' = H;Y = (CH2),;R2 = R3^C2II5;17. N- (2-Ethoxybcnzoyl) -aminobenzoic acid - (// - methyldiethyl-methyl-ammonium) -ethylsier-iodide (R = CH 5 : R '= H; Y = (CH 2 ); R 2 = R 3 ^ C 2 II 5 ;
18. N-(2-Älhoxybenzoyl)-p-aminobenzoesäure-(amethyl-/?-trimelhyl-ammonium)-äthylcster-jodid (R = C,H5; R''=H; Y = CH,-CH-CH2; R2 = R5 = CH,; X = J); Schmp.: 212 bis 214CC (Zers.).18. N- (2-Älhoxybenzoyl) -p-aminobenzoic acid (amethyl - /? - trimelhyl-ammonium) -ethyl ester iodide (R = C, H 5 ; R "= H; Y = CH, -CH-CH 2 ; R 2 = R 5 = CH ,; X = J); M.p .: 212 to 214 C C (dec.).
19. N-(2-Äthoxybenzoyl)-p-aminobenzoesäure-[0-(N-methyl)-piperidinium]-äthylester-jodid (RCHR1 HY(CH)R2R3 19. N- (2-Ethoxybenzoyl) -p-aminobenzoic acid- [0- (N-methyl) -piperidinium] -ethylester-iodid (RCHR 1 HY (CH) R 2 R 3
(25; ;(CH2)2;RR C5H1O;( 25 ;; (CH 2 ) 2 ; RR C 5 H 1O ;
X = J); Schmp.: 238 bis 239° C (Zers.).X = J); M.p .: 238 to 239 ° C (dec.).
20. N-P-tn-ButoxyJ-benzoylj-p-aminobenzocsäure-(/J-diäthyl-methyl-ammonium)-äthylester-jodid (R = Ii-C4H9; R^H; Y = (CH2J2; R2 = R3 = C2H5; X = J); Schmp.: 155 bis 157°C.20. NP-tn-ButoxyJ-benzoylj-p-aminobenzocic acid - (/ I-diethyl-methyl-ammonium) -ethylester-iodid (R = Ii-C 4 H 9 ; R 1 H; Y = (CH 2 J 2 ; R 2 = R 3 = C 2 H 5 ; X = J); m.p .: 155 to 157 ° C.
21. N-P-(n-Amyloxy)-benzoyl]-p-aminobenzoesäure-(/J-diäthyl-methyl-ammonium)-äthylesier-jodid (R = Ii-C5H11; R' = H; Y = (CH2J2; R2 = R3 = C2H5; X=J); Schmp.: 163 bis 166°C.21. NP- (n-amyloxy) -benzoyl] -p- am inobenzoic acid - (/ J-diethyl-methyl-ammonium) -äthylesier-iodid (R = Ii-C 5 H 11 ; R '= H; Y = ( CH 2 J 2 ; R 2 = R 3 = C 2 H 5 ; X = J); m.p .: 163 to 166 ° C.
22. N-P-in-OctyloxyJ-benzoylj-p-aminobenzoesäure-(j?-diäthyl-methyl-ammonium)-äthylester-jodid (R=Ii-C8Hn; R' = H; Y = (CH2)2; R2 = R* = ,5 C2H5; X=J); Schmp.: 136 bis 138°C.22. NP-in-OctyloxyJ-benzoylj-p-aminobenzoic acid (j? -Diethyl-methyl-ammonium) -ethyl ester iodide (R = Ii-C 8 H n ; R '= H; Y = (CH 2 ) 2 ; R 2 = R * = .5 C 2 H 5 ; X = J); M.p .: 136-138 ° C.
23. N-[2-(n-Octyloxy)-benzoyl]-p-amiiiobenzoesäure-(/i-diäthyl-methyl-ammoniumj-äthylester-bromid (R = Ii-C8H17; R' = H; Y = (CH2)2; R2=R3 = C2H5; X = Br); Schmp.: 166 bis 168°C.23. N- [2- (n-Octyloxy) -benzoyl] -p-amiiobenzoic acid - (/ i-diethyl-methyl-ammonium / -ethyl ester bromide (R = Ii-C 8 H 17 ; R '= H; Y = (CH 2 ) 2 ; R 2 = R 3 = C 2 H 5 ; X = Br); m.p .: 166 to 168 ° C.
24. N-[2-(n-Nonyloxy)-benzoyl]-p-aminol>enzoesäure-(/?-diäthyl-methyl-ammonium)-äthylester-bromid (R = Ii-C9H19; R1 = H; Y = (CH2J2; R2 = R-1 = C2H5; X = Br), Schmp.: 147 bis 149°C.24. N- [2- (n-Nonyloxy) -benzoyl] -p-aminol> enzoic acid - (/? - diethyl-methyl-ammonium) -ethyl ester bromide (R = Ii-C 9 H 19 ; R 1 = H ; Y = (CH 2 J 2 ; R 2 = R- 1 = C 2 H 5 ; X = Br), m.p .: 147 to 149 ° C.
25. N-[2-(n-Nonyloxy)-benzoyl]-p-aminobenzoesäure-(/Wiäthyl-methyl-ammonium)-äthylesier-jodid (R = Ii-C9H19; R'=H; Y = (CH2J2; R2=R3 = C2H5; X = J); Schmp.: 127 bis 1300C.25. N- [2- (n-Nonyloxy) -benzoyl] -p-aminobenzoic acid - (/ Wiäthyl-methyl-ammonium) -äthylesier-iodid (R = Ii-C 9 H 19 ; R '= H; Y = ( CH 2 J 2; R 2 = R 3 = C 2 H 5; X = J), m.P .: 127-130 0 C.
26. N-[2-(n-Decyloxy)-benzoyl]-p-aminobenzoesäure-(^-diäthyl-methyl-amnionium)-äthylester-jodid (R = n-C10H21; R1 = H; Y = (CH2J2; R2 = R3 = C2H5; X = J); Schmp.: 115 bis tl7°C.26. N- [2- (n-Decyloxy) -benzoyl] -p-aminobenzoic acid - (^ - diethyl-methyl-amnionium) -ethyl ester iodide (R = nC 10 H 21 ; R 1 = H; Y = (CH 2 J 2 ; R 2 = R 3 = C 2 H 5 ; X = J); m.p .: 115 to t17 ° C.
27. N-[2-(n-Dodecyloxy)-benzoyl]-p-aminobenzoesäure-(y?-diäthyl-methyl-ammonium)-äthylesterjodid (R = Ii-C12H25; R' = K; Y = (CH2J2; R2 = R3 = C2H5; X=J); Schmp.: 81 bis 83°C.27. N- [2- (n-Dodecyloxy) -benzoyl] -p-aminobenzoic acid (y? -Diethyl-methyl-ammonium) -ethyl ester iodide (R = Ii-C 12 H 25 ; R '= K; Y = ( CH 2 J 2 ; R 2 = R 3 = C 2 H 5 ; X = J); m.p .: 81 to 83 ° C.
28. N-(2-Äthoxy-5-chlorbenzoyl)-p-ami:nobenzoesäurc-(/?-diäthyl-methyI-ammonium)-äthyiesterjodid (R = C2H5; R' = C1; Y = (CH2J2; R2 = R3 = C2H5; X = J); Schmp.: 207 bis 2090C.28. N- (2-Ethoxy-5-chlorobenzoyl) -p-ami: nobenzoic acid - (/? - diethyl-methyl-ammonium) -ethyiester iodide (R = C 2 H 5 ; R '= C1; Y = (CH 2 J 2 ; R 2 = R 3 = C 2 H 5 ; X = J); m.p .: 207 to 209 0 C.
Diese Verbindungen weisen eine überlegene antispasmische bzw. spasmolytische Wirkung und coronarerweitermde Eigenschaften auf.These compounds have a superior antispasmodic or spasmolytic effect and coronary widening Properties on.
Die Verfahren werden zunächst an Beispielen (1, Λ bis D) der Herstellung des N-[2-(Buloxy|-bcr.zoyl]-p - aminoberizocsäure - (/; - diätliylamino) - äthylestcrs (Substanz 5) erläutert.The processes are initially based on examples (1, Λ to D) of the preparation of N- [2- (Buloxy | -bcr.zoyl] -p - aminoberizocic acid - (/; - dietliylamino) - ethyl ester (Substance 5) explained.
Beispiel 1 so Example 1 like this
A. 21.20 g (0,1 Mol) o-Butoxybenzoylchlorid und wäßrige lOprozentige NaOH werden bei Raumtemperatur unter Rühren langsam zu 23,63 g (0,1 Mol) p-Aminobenzoesäure-(/J-diäthylamino)-äthylester in cm' Wasser derart zugetropft, daß die Reaktionsmischung leicht alkalisch bleibt. Nach Beendigung der Zugabe wird die Mischung I Stunde lang gerührt.A. 21.20 g (0.1 mol) of o-butoxybenzoyl chloride and aqueous 10 percent NaOH are slowly stirred at room temperature to 23.63 g (0.1 mol) p-Aminobenzoic acid (/ I-diethylamino) ethyl ester in cm 'of water is added dropwise in such a way that the reaction mixture remains slightly alkaline. After the In addition, the mixture is stirred for 1 hour.
Danach wird der Niederschlag abgetrennt, getrocknet und aus Hexan umkristallisiert. Schmp.: 81 bis 82°C.The precipitate is then separated off, dried and recrystallized from hexane. M.p .: 81 to 82 ° C.
B. Zu 31,3 g (0,1 Mol) N-[2-(n-Butoxy)-benzoyl]-paminobenzoesäure in 300 cm3 Äthanol werden 4 g (U, 1 Mol) feingemahlenes NaOH zugesetzt. Das Gemisch wird 1 Stunde am Rückflußkühler erwärmt. Danach werden 20,25 g (0,15 Mol) ß-Diäthylaminoäthylchlorid langsam unter Rühren zugetropft und weitere 4 Stunden erwärmt. Nach dem Abkühlen wird das entstandene Natriumchlorid abfiltriert. Das Lösungsmittel sowie der Überschuß der Base werden unter reduziertem Druck abdestilHert. Der aus Hexan umkristallisierte Rückstand weist einen Schmelzpunkt von 81 bis 82° C auf.B. 4 g (U, 1 mol) of finely ground NaOH are added to 31.3 g (0.1 mol) of N- [2- (n-butoxy) benzoyl] paminobenzoic acid in 300 cm 3 of ethanol. The mixture is refluxed for 1 hour. Then 20.25 g (0.15 mol) of β-diethylaminoethyl chloride are slowly added dropwise with stirring and the mixture is heated for a further 4 hours. After cooling, the sodium chloride formed is filtered off. The solvent and the excess of the base are distilled off under reduced pressure. The residue recrystallized from hexane has a melting point of 81 to 82.degree.
C. Zu 11,7 g (0,1 Mol) 0-Diäthylaminoäthanol in 200 cm3 wasserfreiem Pyridin werden 34,7 g (0,1 Mol) N-[2-(n-Butoxy)-benzoyl]-p-aminobenzoylchlorid vorsichtig zugetropft und die Mischung in einem Wasserbad 3 Stunden lang erwärmt. Danach wird das Lösungsmittel im Vakuum abgetrennt, der Rückstand mit Wasser aufgenommen, alkalisch gemacht und mit Äther extrahiert. Aus den gesammelten Ätherextrakten, die durch die Abtrennung des Lösungsmittels wasserfrei sind, verbleibt ein Rückstand, der aus Hexan umkristaüisiert einen Schmelzpunkt von 81 bis 82CC aufweist.C. To 11.7 g (0.1 mol) of 0-diethylaminoethanol in 200 cm 3 of anhydrous pyridine are 34.7 g (0.1 mol) of N- [2- (n-butoxy) benzoyl] p-aminobenzoyl chloride Carefully added dropwise and the mixture was heated in a water bath for 3 hours. The solvent is then separated off in vacuo, the residue is taken up in water, made alkaline and extracted with ether. From the collected ether extracts, which are anhydrous due to the separation of the solvent, a residue remains which, when converted from hexane, has a melting point of 81 to 82 ° C.
D. Ein Gemisch aus 34.1 g (0,1 Mol) N-[2-(n-Butoxy)-benzoyl]-p-aminobenzoesäureäthylester und 117 g (1 Mol) 0-Diäthylaminoäthanol wird mit einer Lösung von 0.34 g Natrium in 25 g /?-Diäthylaminoäthanol versetzt und unter vermindertem Druck bis zur Trockene destilliert. Der Rückstand zeigt nach wiederholtem Umkristallisieren aus Hexan einen Schmelzpunkt von 81 bis 820C.D. A mixture of 34.1 g (0.1 mol) of N- [2- (n-butoxy) benzoyl] -p-aminobenzoic acid ethyl ester and 117 g (1 mol) of 0-diethylaminoethanol is mixed with a solution of 0.34 g of sodium in 25 g /? - diethylaminoethanol added and distilled to dryness under reduced pressure. After repeated recrystallization from hexane, the residue has a melting point of 81 to 82 ° C.
Zur Herstellung der erfindungsgemäße Verbindungen kann man auch eine substituierte N (2-Alkoxybenzoyl)-p-aminobenzoesäure mit einem Aminoalkohol in Gegenwart von konzentrierter Schwefelsäure oder einen substituierten N-(2-Alkoxybenzoyl)-p-aminobenzoesäure-chloralkylesler mit einem Amin umsetzen. A substituted N (2-alkoxybenzoyl) -p-aminobenzoic acid can also be used to prepare the compounds according to the invention with an amino alcohol in the presence of concentrated sulfuric acid or a substituted N- (2-alkoxybenzoyl) -p-aminobenzoic acid chloroalkyl group react with an amine.
Die Salze können durch Reaktion der entsprechenden tertiären Aminoalkylester mit Methylierungsmitieln. wie Methylchlorid, Methylbromid. Methyljodid oder Methylsulfat, gewonnen werden:The salts can be obtained by reacting the corresponding tertiary aminoalkyl esters with methylating agents. such as methyl chloride, methyl bromide. Methyl iodide or methyl sulfate, are obtained:
Beispiel 2Example 2
Herstellung des Salzes N-[2-(n-Butoxy)-benzoyl]-p-aminobenzoesäure-(/?-diäthyl-methyl-ammonium)-äthylester-jodid (Substanz 20).Production of the salt N- [2- (n-butoxy) -benzoyl] -p-aminobenzoic acid - (/? - diethyl-methyl-ammonium) -ethyl ester iodide (Substance 20).
Zu 41.25 g (0.1 Mol) p-[2-(n-Butoxy)-benzoyl]-aminobenzoesäure-(ß-diäthylamino)-äthylester (Substanz 5) in 400 cm3 Äthanol werden 28,4 g (0.2 Mol) Methyljodid zugegeben und die Mischung bei Raumtemperatur 5 Stunden lang gerührt. Nach Stehen über Nacht wird der Niederschlag abgetrennt. Er weist nach dem Umkristallisieren aus Äthanol einen Schmelzpunkt von 155 bis 157°C auf.28.4 g (0.2 mol) of methyl iodide are added to 41.25 g (0.1 mol) of p- [2- (n-butoxy) benzoyl] aminobenzoic acid (β-diethylamino) ethyl ester (substance 5) in 400 cm 3 of ethanol and the mixture was stirred at room temperature for 5 hours. After standing overnight, the precipitate is separated off. After recrystallization from ethanol, it has a melting point of 155 to 157 ° C.
Claims (1)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT1042966 | 1966-09-27 | ||
| IT2251966 | 1966-09-27 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DE1643458A1 DE1643458A1 (en) | 1971-05-27 |
| DE1643458B2 DE1643458B2 (en) | 1974-10-17 |
| DE1643458C3 true DE1643458C3 (en) | 1975-05-28 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19671643458 Expired DE1643458C3 (en) | 1966-09-27 | 1967-09-15 | N- (2-alkoxybenzoyl) -p-aminobenzoic acid aminoalkyl esters and their quaternary methylammonium derivatives and processes for their preparation |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE1643458C3 (en) |
-
1967
- 1967-09-15 DE DE19671643458 patent/DE1643458C3/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| DE1643458B2 (en) | 1974-10-17 |
| DE1643458A1 (en) | 1971-05-27 |
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