CA1066300A - .omega.-ALKOXY DERIVATIVES OF LACTAMS AND PROCESS FOR THEIR MANUFACTURE - Google Patents
.omega.-ALKOXY DERIVATIVES OF LACTAMS AND PROCESS FOR THEIR MANUFACTUREInfo
- Publication number
- CA1066300A CA1066300A CA268,144A CA268144A CA1066300A CA 1066300 A CA1066300 A CA 1066300A CA 268144 A CA268144 A CA 268144A CA 1066300 A CA1066300 A CA 1066300A
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- Canada
- Prior art keywords
- formula
- carbon atoms
- compound
- lactam
- alkyl radical
- 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.)
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member 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
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
- C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D205/06—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D205/08—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member 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
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
- C07D207/273—2-Pyrrolidones 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 other ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D211/72—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D211/74—Oxygen atoms
- C07D211/76—Oxygen atoms attached in position 2 or 6
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/02—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D223/06—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings 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
- C07D223/08—Oxygen atoms
- C07D223/10—Oxygen atoms attached in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D225/00—Heterocyclic compounds containing rings of more than seven members having one nitrogen atom as the only ring hetero atom
- C07D225/02—Heterocyclic compounds containing rings of more than seven members having one nitrogen atom as the only ring hetero atom not condensed with other rings
-
- C—CHEMISTRY; METALLURGY
- C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
- C25B—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES FOR THE PRODUCTION OF COMPOUNDS OR NON-METALS; APPARATUS THEREFOR
- C25B3/00—Electrolytic production of organic compounds
- C25B3/20—Processes
- C25B3/23—Oxidation
Abstract
Abstract of the disclosure:
Compounds of the formula in which R4 represents an alkyl radical having from 1 to 4 car-bon atoms, R5 represents a linear or branched alkylene radical having from 1 to 10 carbon atoms in the chain which may be substituted by groups which are not reactive under the applied conditions, and R6 represents hydrogen or a branched alkyl radical having from 3 to 10 carbon atoms with a secondary or tertiary N-.alpha.-C atom, are prepared by anodic alkoxylation of lactams of the formula
Compounds of the formula in which R4 represents an alkyl radical having from 1 to 4 car-bon atoms, R5 represents a linear or branched alkylene radical having from 1 to 10 carbon atoms in the chain which may be substituted by groups which are not reactive under the applied conditions, and R6 represents hydrogen or a branched alkyl radical having from 3 to 10 carbon atoms with a secondary or tertiary N-.alpha.-C atom, are prepared by anodic alkoxylation of lactams of the formula
Description
~6~3~
This invention relates -to ~-alkoxy derivatives of lactams and to a process for their manufacture.
It has ~een proposed to react~by an elec-trochemical process, carboxylic acid amides alkylated on the nitrogen atom of the formula 0 \ CH2 ~ R3 :" ' . .
in which R1, R2 and R3 represent hydrogen or organic radicals and R1 and R2 may also be linked with each other, with alcohols -to obtain the corresponding N-~ -alkoxyalkyl carboxylic acid . amides (German OfEenlegungsschrift 2,113,338)~ In this process - the N-alkyl-carboxylic acid amides are electrolyzed in an excess 15 of an alcohol in the presence of a conducting salt, for example an alkali metal or a tetraalkyl ammonium tetrafluoroborate, hexafluorophosphate or nitrate, at a temperature of up to about 00a C. The electrolytic cell may contain a sta-tionary or a flowing electrolyte and the amount of current used does not
This invention relates -to ~-alkoxy derivatives of lactams and to a process for their manufacture.
It has ~een proposed to react~by an elec-trochemical process, carboxylic acid amides alkylated on the nitrogen atom of the formula 0 \ CH2 ~ R3 :" ' . .
in which R1, R2 and R3 represent hydrogen or organic radicals and R1 and R2 may also be linked with each other, with alcohols -to obtain the corresponding N-~ -alkoxyalkyl carboxylic acid . amides (German OfEenlegungsschrift 2,113,338)~ In this process - the N-alkyl-carboxylic acid amides are electrolyzed in an excess 15 of an alcohol in the presence of a conducting salt, for example an alkali metal or a tetraalkyl ammonium tetrafluoroborate, hexafluorophosphate or nitrate, at a temperature of up to about 00a C. The electrolytic cell may contain a sta-tionary or a flowing electrolyte and the amount of current used does not
2~ exceed 2.4 Fararlays per mol of carboxylic acid amide.
It ~as also been proposed (Belgian Patent 837,906~ to ., 1. i ~
electroly~e starting products specifically mentioned in the DOS 2,113,338, i.e. N~alkylcarboxylic acid amides of the "~ formula , ~ i - . ... .
, 1 /
. R - C - N \
29 in which R has the aforesaid mean.ing, in the presence of very :-~ 2 ", ' ' ' ,_ . . . , . ; , ... . . ., . . , ., .. , , , , . ,~ ", . , , ~, . .. .... .
HOE ?5/F 3~0 K
~6~3~
speclfic conducting salts to obtain the corresponding N- ~ -alkoxy-alkyl carboxylic acid amides. In this process higher amounts of current can be used and, hence, -the substance yield is im-proved and, moreover, the reaction mixture can be worked up more easily.
In the aforesaid processes the starting materials used are exclusively N-alkylcarboxylic acids which carry 2 hydrogen atoms ~- in at least one N-alkyl group in ~ -position to the nitrogen and carry also the group CH2-R3 on the nitrogen, especially when R and R are linked with each other.
S-till further, it has been proposed to alkoxylize at the ` -~
anode substantially in the same manner those N-alkylcarboxylic -;
acid amides which carry on the nitrogen atom two alkyl groups linked wi-th each other (cf. German Offenlegungsschrit 2j539,777).
In the latter process the starting compounds have the ormula .,.~ ' .
C~I
R1 _ C - N \ R2 ., - '\~C ~ ...
` ' in which R1 has the aforesaid meaning and ~2 represen~ a linear or branched alkylene radical having from 1 to 4 carbon atoms in - the cha;n. Depending on the current amount used, the alkoxylation ~ -`i is effected on one or on both of the CH2 groups linked to the ~ nitrogen atom.
.~. . .
In the anodic alkoxylation of the N-alkylcarboxylic acid amides used according to the process of DOS 2,113,338 it is prac-tically alw~ys the CH2 group of the CH2-R3 substituent which is , .
~` alkoxylated even i the radicals R1 and R2 are linked with each
It ~as also been proposed (Belgian Patent 837,906~ to ., 1. i ~
electroly~e starting products specifically mentioned in the DOS 2,113,338, i.e. N~alkylcarboxylic acid amides of the "~ formula , ~ i - . ... .
, 1 /
. R - C - N \
29 in which R has the aforesaid mean.ing, in the presence of very :-~ 2 ", ' ' ' ,_ . . . , . ; , ... . . ., . . , ., .. , , , , . ,~ ", . , , ~, . .. .... .
HOE ?5/F 3~0 K
~6~3~
speclfic conducting salts to obtain the corresponding N- ~ -alkoxy-alkyl carboxylic acid amides. In this process higher amounts of current can be used and, hence, -the substance yield is im-proved and, moreover, the reaction mixture can be worked up more easily.
In the aforesaid processes the starting materials used are exclusively N-alkylcarboxylic acids which carry 2 hydrogen atoms ~- in at least one N-alkyl group in ~ -position to the nitrogen and carry also the group CH2-R3 on the nitrogen, especially when R and R are linked with each other.
S-till further, it has been proposed to alkoxylize at the ` -~
anode substantially in the same manner those N-alkylcarboxylic -;
acid amides which carry on the nitrogen atom two alkyl groups linked wi-th each other (cf. German Offenlegungsschrit 2j539,777).
In the latter process the starting compounds have the ormula .,.~ ' .
C~I
R1 _ C - N \ R2 ., - '\~C ~ ...
` ' in which R1 has the aforesaid meaning and ~2 represen~ a linear or branched alkylene radical having from 1 to 4 carbon atoms in - the cha;n. Depending on the current amount used, the alkoxylation ~ -`i is effected on one or on both of the CH2 groups linked to the ~ nitrogen atom.
.~. . .
In the anodic alkoxylation of the N-alkylcarboxylic acid amides used according to the process of DOS 2,113,338 it is prac-tically alw~ys the CH2 group of the CH2-R3 substituent which is , .
~` alkoxylated even i the radicals R1 and R2 are linked with each
3 - ~
: . .
-63~
other, i.e. Iactams substi-tuted at the nitrogen atom b~ the ~roup CH2--R . Produc~ alkoxy]ated on the nucleus, that is to say ln the lactam ring, are practicall~ not formed.
There are known pure]y chemical reactions to prepare lactams which addi-tionally carry an alkoxy cJroup on the carbon atom ad-jacent to the nitrogen atom (opposite to the carbonyl group).
Compounds of this type can also be considered N,O-acetals. A
chemical method to prepare these compounds is described, for exarnple, in I.iebigs Ann. Chem. 1974, pages 539 - 560, according to whlch the four-membered ring compounds are prepared, in prin-ciple, by the following reaction equation: -, ~CO F~COO~
R-~OO~I=C~ * SO~Cl - ~ N ~ \ ~~
vinyl es~er chlorosulfonyl H O
lsocyanate ... .
R'O
R'~H
~; ~ > ¦ ~ ~COOH
,l alkaline ~ t solution . .
., .
... .
~ ~ in which ~ and R' represent organic radicals.
;.
A generalization of this method for the prepara-tion of ~I N,O-acetals with higher rings has not yet ~ecome known.
In view of the fact that N,O-acetals of this type are im-portant intermediates it is desirable to develop a process per-mitting the preparation of such compounds in a simple and uncom-plicated manner independent of the size of the lactam ring.
- This problem could be solved by further developing the alkoxylation reaction described in German Offenlegungsschrift -, , . . ':
.
, , ~ , , . ,, , ": :
... .. . . ,.. , . . , , , . . " ,, ... , , , . ~ , .. :. ~ . . ~, HOE 75/F 340_K
:~066~
2,113,338 and i.n Belgian Patent 837,906.
It is therefore the object of the present invention to use as startin~ materials for the electrolysis lactams of the formula ~: I CH2 ~ ' I I .
- C - N
~-~ in which R represents a linear or branched alkylene radical having ` -from 1 to 10 carbon atoms in the chain which may be substi~
:~ tuted by groups which are not reactive under the applied .~ conditions, for example hydroxyl or halogen, preferred substituents of R being CH207I-, -CH2-A-CH2CH2CH2-COOR
in which A represents -C~C-, -CH=CH- or -CH2-CH2- and R7 stands for hydrogen or a low molecular weight aliphatic ... .
.~ ~C1~C4), cycloaliphatic (C5-C6) or araliphatic (C6-C8) hydro-- carbon radical, .~ R6 represents hydro~en or a branched alkyl radical preEerably ` havin~ ~rom 3 to 10 carbon atoms with a secondary or tertiary .. ~ N-~ -C atom which is difficul-t to alkoxyl~ate.
: The present invention provides a process for the anodic .,~, . . .
.~ : alkoxylation of N-alkylcarboxylic acid amides with an alcohol of the formula R40H in which R4 represents an alkyl radical .. : having from 1 to 4 carbon atoms, ln thè presence of at least one alkali metal or tetraalkylammonium tetrafluoroborate, hexa-fluorophosphate or nitrate as conductlng saltj at a temperature of ~Ip to about ~OO C in an electrolytic cell with stationary or flowing electrolyte, which comprises using as N-alkyl carb--o~ylic ac;d amide a lactam of the formula ~ 5 ~
~,. . . ; ,. .. , .. . ... , ;: . ~:
~6G300 s f C - N
.
. .
in which R5 and R6 have the aforesaid meaning. The reaction yields lactams alkoxylated in the nucleus and having the follow-;~ing formula ., oR4 R -- CH
., , I I ~ '',,,'',,.
~ C ~ N
.
, Suitable starting compounds in the process of the invention !~; are, for example, azetidinone-2, 3-methyl-azetidinone-2, 1-iso-pxopylpyrrolidone-2, 1-isopropyl-4-hydroxymethyl-pyrrolidone-2, : 1-isopropyl-3-~6-carbome~hoxy-2-hexine-yl(1~7-4-hydroxymethyl-.
pyrrolidone-2, 1-tert.-butylpyrrolidone-2, pip~ridone-2, ~ -ca-~i~ prolactam, the lactams of ~amino~caprylic acid, capric acid, lauric acid, preferably, however, 1~isopropyl-4-hydroxymethyl-pyrrolidone-~2, compounds of the formula C ~ ~ A ~ ~
O
: R7 ,C - N G
. ., : .I~ ~ in whlch ~' represents a C1-C4 alkyl radical, a C5-C6 cycloalkyl :~ ~ radical or an araliphatic radical, and ~ore preferably 1-isopropyl ~ 3-~6-carbom~thoxy-2-hexine~yl(1)_?-4-hydroxymethyl-pyrrolidone-2, ~;,: ::
~ 6~
, . ~ :
.j ~ . , ~663~10 HOE 7~/F 340 K
(in whieh A i.s -C-C-, R is / CH3, R7 is CH3), -CH
-\ CH3 ~ whieh eompounds ean be prepared as deseribed in German Offen-:: 5 legungssehrif-ten 2,452,536 and 2,528,036 aceording to -the foLlow- ing reaction scheme:
~ 00~ ~2~
.~ ~ ~ -.
. ~ reduction r .~ ~ th~rif i.c.~tion O .__ ~6 ~; CN
Cl ~ C~-alkyl rad~eal~
.
` C~I20~ ,, .
J~ ' ' '.
.:; ~C ~ ~R~ Cl~?-~C~2`~H2-(NaH) `'(n9 ~ protective group which ean be readily split off under aeid : eonditions - . . .
C~2 ,~ C~ KCN ~ NC~ ~ ~ ~ oR9 ,;` ~C _ N'`R6 ~ ~ \R6 -20-es~e~ifi~ation (n7H~ ~'H~O~
~ ~ 7 ~ ~ \
;30 s~litting of of . I
: K~ in:an acid medium ~ C - N
O R~
~ . . .
~ 7 ;, ' ~ ' ' , . :
.
; , ' . '. , " ~ "' . :' ' ' . , ' . '' ;'. " , ' '; '.~ '.. ' ' " ' " . . '.' ' . ' ~ HOE 75/F 340 K
In the case of A being -C-C- the final compound can be partlally hydrogenated to form the -CH=CH- group or completely hydrogenated to -CH2-CH2- by a method known per se.
With the use of the preferred starting compounds the following final compounds are obtained:
~ f ~ R
O~ CH-CH3 ;.
H~/CH2 oH
R OO(~\/\ A ~--~OR and O
.~
.
;~ H CH2H
CooC \ ~ ~ ~ H
. ............................................ ~ I ~ oR4 C -- N
~H-CH3 Products of this type are novelO They can be used as inter-; mediates for the manufacture of pharmaceuticals, especially :~ those having prostaglandine-like effects (cf. United States Patent 4,096,274 issued to Hoechst AG on June 20, 1978) A pharmaceutical of this type is, for example, the compound ;, of the formula :
` ' . ' ` ' , ' '.' f ' ' ;.' ~ , . , I ' ; ' ' ' ' , , ', ,.' ~ ' ., " ~ . ;, ' ' " ' HOE 75/F ~0 K
0~
H ~I~ - CII - C~I ~ R
C - N
~H ~ CH3 .
obtained by oxydation of the CH20H group in the latter compound ~o -the CMO group, reac-ion with o .~ (RO)2P - C~12 - C - R
; O
in which each R stands for an al~yl radical and the radica] R
bound to the C-group may also represent an optionalLy substituted ' ~ phenoxy or cycloalkyl radical, and hydrogenation of the azeto-: carbonyl yroup.
~.; Fu.rther preferred starting compounds ln the process of the :.~ invention are lactams with 5 to 13 ring members of the oxmula R - CH
~C - - N
R
: - in which R represents -(CH2)2_10, preferably -~CH2)3-, -(CH2) 4 and (CH2) 1O-~
R6 stands for hydro~Jen or a branched alkyl radical hav.ing from 3 to 10 carbon atoms with a secondary or tertiary N-~ -C
atom, preerably hydrogen.
,,, q. ~ :
.,'' . ` :
:, ~ : ; ~ : -: . . . . . . , , ,-; . :.. : ,, :.:
The compounds obtained ln this manner are also novel, they have -the :Eormula R5 - CH - oR4 I I
oD R
in which R5 and R~ have the aforesaid meaning, R4 represents an alkyl radi-cal with -I to 4 carbon atoms preferably CH3.
Com~ounds of t:his type can be used as antistatic agents in tex-tl:Le industries and as intermediates in polymerization reactions and in the preparation.o:E ~ -amino~ -dicarbo~y~lic acids according to the following reaction scheme:
` R5 - - ~ CH - OCH
3 methanolic >
mineral acid C - N
0R - :
El3COOC-E' - CH(OCEl3)2 > + HCN/NEI~HCO3 . ~ H2NR - (Strecker-Bucherer~' reaction) : .
H COOC-R5 ~ CH - CO + HCl .:
3 1 1 (acid hydrolysis) "' \ / :
C , . .
':~ o ., .
; HOOC-R -CEI~COOH
. NH2 ~ 10 -., ~ . .
, ~ . .
: ~
... , . . , .: : j, , : :. ~. ' . : , . ~ .: ~ . .; . .
. ,, ~, . . . . . .
~36~3~al Suitab].e a].cohols R~OH to carry out the process of the invent:ion are methanol, ethanol, n-propanol, isopropanol, n~
butanol5sec.-bu-tanol, preferably, however, methanol and ethanol and more preferably methanol.
The conducting salt to be used in the process of the inven-tion are alkal;. metal salts (Li, Na, K, Rb, Cs) and tetraalkyl ammoni~lm salts of tetraEluoroboric acid, hexafluorophosphori.c acid and nitric acid. They are used either singly or in admix--ture with one another. The alkyl radicals in the tetraalkyl ammonium group have 1 to 6 and preferably 1 to 4 carbon atoms, : especially the methyl and ethyl radical. The ollowi.ng conduct-~
ing salts are mentioned by way of example: :
Na-tetrafluoroborate, Na--nitrate, K--tetrafluoroborate., K-he~a-. fluorophosphate, Rb-nitrate, te-tramethylammonium tetrafluoro-'~ 15 borate, tetraethylammonium tetrafluoroborate, tetra-n-butyl-; ammonium tetrafluoroborate, -tetraethylammonium hexafluorophos~
phate, tetra-n-propylammonium hexafluorophosphate tetra-n butyl-ammonium hexafluorophosphate, or tetramethylammonium nitrate.
Preferred conducting salts are the alkali metal and tetraalkyl ~0 ammonium tetra-fluorobor~te~ especially NaBF4, KBF4 and (CH3)4-. MBF4.
I'he concentrat~on of conducting salt i.n the electrolysis solution should be ;n the range of Erom about 0~01 to about .
2.0 mol/lt preferably about 0.02 to 1.0 mol/l. The temperature of ~he electrolys~s solution should be in the range of from ~-~ about -10 to t l 00 C, preferably about 0 to 60 C.
.. : . In the electrolytic solution -the molar proportion of start-ing acid amide to alcohol is in the range oE Erom about 1:1 to 29 about 1:100, preferably 1:~ to 1:60 and more preferably 1:5 -to . '- ~ 1 ~ .
- ~ , ~OE 75/F 340 K
~ 3 1:50.
The electroc~i~emical alkoxylation accorcling to the invention may be carried out discontinuously or continuously.
The process will now be described in ~ur-ther detail by way of example only, with reference to the accompanying d~awing which is a ~iew, partly in section, of an ~lectrolysis cell suitable for carrying out the process of the invention in dis-continuous manner.
Referring to the drawing, an electrolytic cell (1) is equipped ~ith a tightly sealing cover or lid (2), through which the power supply lines for electrodes (3) and (4) are led and in which an opening (5) for the supply of the electrolysis solu-tion, an opening (6) for -the discharge of gas and a thermometer (9? are fi;~ted. The oriEice (6) for the discharge of gas may be equippeA with a reElux condenser, in which evaporating por-tiOllS of the electrolysis mixture may be recovered by conclensa-tion. The electrolytic cell (I) is encased and may be connected to a heatin~ or coolin~ llquid circuit by means of inlet and out let soc]~ets (7 and 8). The temperature of the electrolysis solu-2~ tion ~s controlled by the thermometer (9) or A thermosensor. Thetwo electrodes (3) tanode) and (4) (cathode) are set up at a ~1 distance of from 0.5 to 50 mm, preferably from 1 to 15 mm.
As electrodes there are used nets or sheets of palla~ium or platinum or noble~metal-coated metal elec-trodes, preferably titanium electrodes, mixed oxide-coated metal electrodes (as anodes), preferably titanium anodes, or graphite plates provided with slits or nOt. The use of electrode nets is especially ad-vantageous, because these facilitate the dîscharge of the gaseous 29 hydrogen formed during the electrolysis, and the uniEorm and ;
` - 12 _ .,.~ ~ ^
.' ' ' ... . . . . ' .. : '. . , . : ! ' ~ , . '~
_E75 /F 340 K
~C~6~
-thorough mixture of the electrolysis solution is additionally ~avollred by the yas current formed. The vertical disposition of the electrodes may be replaced, if desired, by a }~orizontal one. It is also possible to use several electrode pairs; a bloc~-like combination of anyular or non-angular capillary split electrodes, optional wi-th vibration oE the electrodes, has proved especially ef~icient. The so]u-tion is mixed vigorously during electrolysis by means of an agitator, for example a magnetic stirrer (10) or by circulation by pumping, especially in case of the block-like combinations.
If the process is carried out continuously, an addi-tional orifice may be set in the cover (2) of the elec-trolysis vessel for pump-circula-ting the electrolysis solution continuously.
~ portion of the electrolysis solution which is circulated by pumping is separated for work up of the product. ~fter deter-mination o~ the ratio of the desired reaction product to the starting m~terial in the electrolysis solution by the nuclear magnetic resonance spectrum or by gas chromatography t the solu-tion is worked up in known manner. The starting ma-terials, re-covered upon distillation, may be adjusted to ~he molar ratio empLoyed and then metered into the continuo1lsly reclrculating electrolysis solution together with the required quantity of the conductin~ salt or salts.
The electrolysis may be carried out under normal pressure, ~ut may be performed under reduced pressure. So as to avoid the ~ormation of explosive gas mixtures of hydrogen and air, the addition oE an inert gas, e g. nitrogen, is advantageousO
The conducting salt is suitably added aEter having prepared - 29 the alcoholic solut:Lon. However, tl-lis order may be chanyed.
- ~3 -. . - . :
- . . . ~.: ; -: : : . : ::; ~ . :
,, ., . - .. ... .. . . . . . . ..
: , : : : , . . : . . : . .
: . : : : . : . - ~ . , , . . ; ,: :
.. . . . . . ~
~IOE 75~F 3~0 K
~663~
There is no need to e~clude wa-ter strictly from the electro-lyte since mlnor amounts thereof do not affect the course oE
xeaction.
~he process gives an esp~cially high yield and is especially efficient with respect to ener~y consumed, if the conversion of cyclic carboxylic acid amide is increased, e.g. to more than 99 %, this step being also advanta~eous ~or a better work up o~ the electrolysis solution. There~ore, the electrolysis is advanta~eously continued until practically the total starting material is converted so that there is no need later to separate this from ~he the reac-tion product.
The electrolysis current is switched off after having led through the ~uantity of electricity desired, and the electroly-sis discharge is then freed from the conducting salt and worked up in knor~n manner, preEerably by dis~illa-tion. The de~ree of purity of the product may be determined by a nuclear magnetic resonance spectrum.
The current density is chosen in the range of from about 1 to 50 ~/dm , preferably 2 to 30 A/dm2. Lower current den-sities are also possible, though they diminish the rate at which the product is formed. The quantity of electricity should be about 2 to 4, preferably 2 to 3.5 and especially 2 to 3 Faradays/mol of startin~ lactam.
The ~-alkoxy derivatives of cyclic carbox~lic acid amides prepared a~cordin~ to the electrochemical process of the in~ention are valua~le intermediate produc-ts, especially for the manu~ac-ture of pharmaceuticals, having, in the first place, prosta~lan-- dine like effects and also luteolytic, bronchospasmolytic and/or 2~ antihypertensive properties and properties to inhibit the secre~
~, . . , .: . : . :
. . .. . .
: ~ ; ,: ' ' ' , '. ' :,: ' ~, . .
OE 75/F _~0 ~
~63~1~
-tion of gastrie juiee, The following e~amples illustrate the invention.
17.6 cJ of azetidinone-2- and . 5 39.6 g of methanol are electrolyzed in an electroly-tic cell havincJ a capaci-ty oE
approximately 60 ml in the presence oE 0.82 g of tetra-m-propyl-ammonium he~aEluorophosphate as conducting salt. As eleetrodes two eoncentrically placed platinum net cylinders having 225 10 mesl1es per cm2 and diameters of 1S and 30 mm, respect~vely, and a height of 50 mm are immersed in the solution~ the outer . electrode ~eing conneeted as anode. During elee-trolysis the temperature is maintained at about 10 C. After haviny switched on the el.ectrolysi.sdirect current, the current densi-ty at the anode is i ~/~m2. The eurrent i.s switehed off after passage of :~ 2.5 Faradays per mol of azetidirlone-2~ The ealeulated average . eell tension is 29.6 volts. After working up by moleeular distil-lation there are obtainecl 12.7 g of ~-methoxy-azetidinone-2 : (~oiling point ~1 C under 0.013 millibax, melting point 62 - -`:
` 2Q 63 C)~ corresponding to a material yield of 50.9 % and a eurrent .
efficieney of ~0.7 ~. :
E ~ A M P L E 2:
In an eleetrolytie eell as described in Example 1 ~` 2l.0 ~ of pyrroli~one-2 and :: 25 39.6 g of methanol are eleetr~lyzed in the presenee of 0.40 g of tetramethyl-ammonium tetrafluoroborate as eondueting salt. After having switehed on the electrolysis direet eurrent~the density at the 29 anode is 3 ~/dm2 r The eurrent i5 switehed off after the pas~ :
~ 15 ~
. ~ :
::
: : : : . . :: :. , . , : : , . :- : .
. . : . , ~ . .. ~ . , . .. : . , : .. . :
~1663~
sage o:E 2.~ Faradays per mol of pyrrolidone-2~ The calculated averacle cell tension is 35.2 volts. After working up by mole-cular distillation, 14.3 g of S-methoxypyrrolidone~2 are ob-tained (boiling poin-t 87 - 90 C under 0.14 millibar, melting poin-t 56 - 58qC~correspondi~ng to a material yield and a current eff.iciency of 50.1 ~ each.
In an electrolytic cell as described in Example 1 ~ .7 g of pyrrol:idone-2 and 10 39.5 g cf e-thanol are electxolyzed in the presence of 0.28 g of tetramethyl ammonium te-trafluoro~orate as conducting salt. After having switched on the electrolysis direct current,the anode current density is 3 A/dm2. After having passecl 2.0 Faradaysper mol o:E
lS pyrroli.done-2 -the current is switched off. The calcula-ted average .` cell tension is 48.2 volts.
: ~orking up by molecular distillat;on yields12.0 g of 5-. ethoxypyrrolidone~2 (melting point 54 - 56 C), corxesponding to a material yield and a current efficiency of 54.2 % each.
E X A M P L E 4:
~' In an electroly-tic cell as described in Example ~
~0.0 o 1~isopropyl-4-hydroxymethylpyrrolidone and 54.6 g of methanol are electroly~ed in the presence of 0.34 g of tetramethylammonium tetrafluoroborate as conducting salt. After having switched on ~ the electrolysis direct current,-the anode current density is 2 A/dmZ. ~fter the passage of 2.2 Faradays per mol of l-iso- :
propyl~4-hydroxymethylpyrrolidone,the current is switched off.
~ 29 The calculated average cell tension is 43.5 volts.
.` l~i`
- - .
, HOE 75/F 3~0 K
~06~3~0 ~:E-ter separation of the methanol and separation by columr chromatography (sllica ~el/chloroform + ethanol ~9 17) 9.0 g of 1-isopropyl--4-hydroxymethyl-5-methoxypyrrolidone-2 are obtained, corresponding to a material yield of 75.6 ~ and a current efficiency of 68.7 %.
NMR characteri~.tics of the compound:
NMR 100 millicyles per second; solvent: CDCl3; N-CH: 4.1 ppm /C~3 - N- :1.2 ppm -O-CH3- 3.3 ppm . E X A M P L E 5:
a) Preparation of 1-meth~l- and 1-isopro~vl-3- ~-carbomethoxy-2-hexiIle-y _1)7-~l-hydroxymeth~l-~yrrolidone 1-methyl com~ound ~) - 29.~ g (l38 mols) of 1-methyl--4-(2-tetrahydropyranyl-hydroxyn~ethyl)-pyrrolidone dissolved in 90 ml of diethyl ether are added ovex a peri.ocl of 20 m.Lnutes while stirring at -70~ C to 1S0 mols of LiN(i-C3H7)2 in 150 ml of diethyl ether. Stlrring is continued for 45 minutes whereupon the ~ solution is transferred to a coolable dropping funnel (-35 :: to -40 C) and added, while s-tirring over a periocl of 60 , .
.. minutes, to a solution cooled to -70 C of 29.1 g (149 mols) of 1-bromo-6-chloro-hexine(2~ in 135 ml of ether~ Stirring is continued for another 90 minutes, -the mixture is slowly .. ~ heated to room temperature, 75 ml of water a.re added drop~
; wise, the organic phase is separated ancI the aqueous phase is extracted tnree -times, each time with 50 ml of diethyl - 29 ether. The combined ether phases are washed three times .: , . .
~; - 17 ~ .
. ' , . ` .
.. - . . . . . .
`:, ''''~ ' ' '' ,' ,, ` ; ,' ~ ': ,.. : ' ' ` `', " '. ' `' , . . . . :, ~6~3~
with 40 ml each of cold sulfuric acid and once with 50 m].
of wa-ter. Af-ter drylng and concentrating under reduced pressure the organic phase, 46.6 g of crude 1-methyl-3-~6-chloro-2-hexine-yl(1)~-4-(2--tetrahydropyranyl-hydroxy-5 methyl) pyrrolidone (RF 0.42 (ethyl acetate)) are obtained The compound is used for the following reac-ti.on stage with-out further purification.
~) 7.5 y (153 mols) of sodium cyanide are dissolved in 90 ml of dimet11yl sulfoxide and the solu-tion is heated to 80 C. 46.6 g (142.5 mmols) of crude 1-methyl-3-~6-chloro-2-hexine-yl(1)~-4-(2-tetrahydropyranyl-hydroxymethyl)-pyrro-lidone dissolved in 40 ml dimethyl sulfoxide are then added dropwi.se while stirring and -the mixture is stirred for 3 to 6 hours at 80 C. The course of the reaction is followed ~y thi.l~ layer chroma-tography (e-thyl aceta-te~. When the reaction is termini~ted, the mix-ture is cooled to 10 C, 200 ml of water are added and the mixture is extracted . three times, each tlme with 200 m]. of diethyl ether. The .~ combined ether phases are washed -three times with saturated sodi.um chloride solution and dried. After concentration ~: under reduced pressure 43.7 g of crude 1-methyl-3-L6-cyano-.
- 2-hexine-yl(1)J-4-(2-tetrahydropyranyl-hydroxyme-thyl)-pyrro-. lidone ~RF 0 39 (ethyl acetate)~ are obtained, which is used ` for the next reaction without further purification.
:, 25 ~) 11 g (0.275 mol) of sodium hydroxide are di.ssolved in 33 ml of water, 43.7 g (]37.5 mols) of 1-methyl-3-~6-cyano-- . 2-hexine-yl(1)~-4-(2-tetrahydropyranyl-hydroxymethyl)-pyrro~
~ lidone dissolved in 135 ml of ethyl alcohol are added and :" 29 the whole is refluced for 18 hoursO The alcohol is removed ~ 18 -663~
under reduced pressure, 150 ml of icecold 2N sulfuric acld are aclded to the residue while cooling with ice and the whole is e~tracted ten times, each time with 100 ml of c1l-ethyl ether. After drying ~nd concentrating the combined ether phases, 47.4 g of crude 1-methyl-3-f6-carbohydroxy-2-hexine-yl)~-4-(2-tetrahydropyranyl-hydro~ymethyl)-pyrroli-done are obtalned which is direc-tly taken up in 250 ml of methylene chloride and to which 380 ml of a 0.5 molar ethereal diazomethane solution are adc1ecl a-t 0 C. The mixture is allowed to stand for 30 minutes at 0 C and for 1 hour at room temperature. After concentration under re-duced pressure~43.7 g of crude 1-methyl-3 r6-carbomethoxy-2-hexine~yl(l)~-4-(2-tetrahydropyranyl-hydroxymethyl)-pyrro-. 1idOne rRF . 45 (ethyl acetate)~ are ob-tained.
~ The product obtained is dissolved in 200 ml o metha-~` nol, 3 drops oE concentrated hydrochloric acicl are added and the mixture is refluxecl for 75 minutes. ~fter concen-~
tratil1g und~r reduced pressure~ the remainin~ oil i.5 puri-fied by column chromatography (siliea gel/ethyl acetate) 2~ to remove by-products, then ethyl acetaie:ethanol 10-1.5).
` 25 y of 1-methyl-3-/6-carbomethoxy-2-hexine-yl(1).~-4-hy-droxy~ethyl-pyrro~idone ~RF 0.14 (ethyl acetate)? are ob-~
tained.
nD = 1.5005 IR(CH Cl2): = 3450 (OH), 1740 (C=O), 1690 (C=~ cm 1 ` 2 NMR,solvent: CDCl3:N-CH3: 2~82 ppm; 0-CH3: 3.64 ppm.
1-iso~ro~l com~ound ., ~____ _ _ :.
Thls eompound is prepared in analogous manner using . ~
29 as starting compound 1-isopropyl-4-(tetrahydropyranyl-hy-. .
, . ' /
, . , . ::
. . .
- ; . ,~. ~ . ,. .: .
.
.
~166313~
dro~yme-thvl)-pyrrolidone.
nD = 1.4945 ~ CH3 NMR: solvent: CDCl3; OCH3 3.63 ppm N~ 14 ppm;
M- CH : 4.23 ppm.
b) Anoc~ic oxidatlon of the 1-isopropyl compound In an electrolytic cell having a capacity of about 60 ml 5.0 g of 1-isopropyl-3-~ -carbomethoxy-2 hexine-yl(1)J-
: . .
-63~
other, i.e. Iactams substi-tuted at the nitrogen atom b~ the ~roup CH2--R . Produc~ alkoxy]ated on the nucleus, that is to say ln the lactam ring, are practicall~ not formed.
There are known pure]y chemical reactions to prepare lactams which addi-tionally carry an alkoxy cJroup on the carbon atom ad-jacent to the nitrogen atom (opposite to the carbonyl group).
Compounds of this type can also be considered N,O-acetals. A
chemical method to prepare these compounds is described, for exarnple, in I.iebigs Ann. Chem. 1974, pages 539 - 560, according to whlch the four-membered ring compounds are prepared, in prin-ciple, by the following reaction equation: -, ~CO F~COO~
R-~OO~I=C~ * SO~Cl - ~ N ~ \ ~~
vinyl es~er chlorosulfonyl H O
lsocyanate ... .
R'O
R'~H
~; ~ > ¦ ~ ~COOH
,l alkaline ~ t solution . .
., .
... .
~ ~ in which ~ and R' represent organic radicals.
;.
A generalization of this method for the prepara-tion of ~I N,O-acetals with higher rings has not yet ~ecome known.
In view of the fact that N,O-acetals of this type are im-portant intermediates it is desirable to develop a process per-mitting the preparation of such compounds in a simple and uncom-plicated manner independent of the size of the lactam ring.
- This problem could be solved by further developing the alkoxylation reaction described in German Offenlegungsschrift -, , . . ':
.
, , ~ , , . ,, , ": :
... .. . . ,.. , . . , , , . . " ,, ... , , , . ~ , .. :. ~ . . ~, HOE 75/F 340_K
:~066~
2,113,338 and i.n Belgian Patent 837,906.
It is therefore the object of the present invention to use as startin~ materials for the electrolysis lactams of the formula ~: I CH2 ~ ' I I .
- C - N
~-~ in which R represents a linear or branched alkylene radical having ` -from 1 to 10 carbon atoms in the chain which may be substi~
:~ tuted by groups which are not reactive under the applied .~ conditions, for example hydroxyl or halogen, preferred substituents of R being CH207I-, -CH2-A-CH2CH2CH2-COOR
in which A represents -C~C-, -CH=CH- or -CH2-CH2- and R7 stands for hydrogen or a low molecular weight aliphatic ... .
.~ ~C1~C4), cycloaliphatic (C5-C6) or araliphatic (C6-C8) hydro-- carbon radical, .~ R6 represents hydro~en or a branched alkyl radical preEerably ` havin~ ~rom 3 to 10 carbon atoms with a secondary or tertiary .. ~ N-~ -C atom which is difficul-t to alkoxyl~ate.
: The present invention provides a process for the anodic .,~, . . .
.~ : alkoxylation of N-alkylcarboxylic acid amides with an alcohol of the formula R40H in which R4 represents an alkyl radical .. : having from 1 to 4 carbon atoms, ln thè presence of at least one alkali metal or tetraalkylammonium tetrafluoroborate, hexa-fluorophosphate or nitrate as conductlng saltj at a temperature of ~Ip to about ~OO C in an electrolytic cell with stationary or flowing electrolyte, which comprises using as N-alkyl carb--o~ylic ac;d amide a lactam of the formula ~ 5 ~
~,. . . ; ,. .. , .. . ... , ;: . ~:
~6G300 s f C - N
.
. .
in which R5 and R6 have the aforesaid meaning. The reaction yields lactams alkoxylated in the nucleus and having the follow-;~ing formula ., oR4 R -- CH
., , I I ~ '',,,'',,.
~ C ~ N
.
, Suitable starting compounds in the process of the invention !~; are, for example, azetidinone-2, 3-methyl-azetidinone-2, 1-iso-pxopylpyrrolidone-2, 1-isopropyl-4-hydroxymethyl-pyrrolidone-2, : 1-isopropyl-3-~6-carbome~hoxy-2-hexine-yl(1~7-4-hydroxymethyl-.
pyrrolidone-2, 1-tert.-butylpyrrolidone-2, pip~ridone-2, ~ -ca-~i~ prolactam, the lactams of ~amino~caprylic acid, capric acid, lauric acid, preferably, however, 1~isopropyl-4-hydroxymethyl-pyrrolidone-~2, compounds of the formula C ~ ~ A ~ ~
O
: R7 ,C - N G
. ., : .I~ ~ in whlch ~' represents a C1-C4 alkyl radical, a C5-C6 cycloalkyl :~ ~ radical or an araliphatic radical, and ~ore preferably 1-isopropyl ~ 3-~6-carbom~thoxy-2-hexine~yl(1)_?-4-hydroxymethyl-pyrrolidone-2, ~;,: ::
~ 6~
, . ~ :
.j ~ . , ~663~10 HOE 7~/F 340 K
(in whieh A i.s -C-C-, R is / CH3, R7 is CH3), -CH
-\ CH3 ~ whieh eompounds ean be prepared as deseribed in German Offen-:: 5 legungssehrif-ten 2,452,536 and 2,528,036 aceording to -the foLlow- ing reaction scheme:
~ 00~ ~2~
.~ ~ ~ -.
. ~ reduction r .~ ~ th~rif i.c.~tion O .__ ~6 ~; CN
Cl ~ C~-alkyl rad~eal~
.
` C~I20~ ,, .
J~ ' ' '.
.:; ~C ~ ~R~ Cl~?-~C~2`~H2-(NaH) `'(n9 ~ protective group which ean be readily split off under aeid : eonditions - . . .
C~2 ,~ C~ KCN ~ NC~ ~ ~ ~ oR9 ,;` ~C _ N'`R6 ~ ~ \R6 -20-es~e~ifi~ation (n7H~ ~'H~O~
~ ~ 7 ~ ~ \
;30 s~litting of of . I
: K~ in:an acid medium ~ C - N
O R~
~ . . .
~ 7 ;, ' ~ ' ' , . :
.
; , ' . '. , " ~ "' . :' ' ' . , ' . '' ;'. " , ' '; '.~ '.. ' ' " ' " . . '.' ' . ' ~ HOE 75/F 340 K
In the case of A being -C-C- the final compound can be partlally hydrogenated to form the -CH=CH- group or completely hydrogenated to -CH2-CH2- by a method known per se.
With the use of the preferred starting compounds the following final compounds are obtained:
~ f ~ R
O~ CH-CH3 ;.
H~/CH2 oH
R OO(~\/\ A ~--~OR and O
.~
.
;~ H CH2H
CooC \ ~ ~ ~ H
. ............................................ ~ I ~ oR4 C -- N
~H-CH3 Products of this type are novelO They can be used as inter-; mediates for the manufacture of pharmaceuticals, especially :~ those having prostaglandine-like effects (cf. United States Patent 4,096,274 issued to Hoechst AG on June 20, 1978) A pharmaceutical of this type is, for example, the compound ;, of the formula :
` ' . ' ` ' , ' '.' f ' ' ;.' ~ , . , I ' ; ' ' ' ' , , ', ,.' ~ ' ., " ~ . ;, ' ' " ' HOE 75/F ~0 K
0~
H ~I~ - CII - C~I ~ R
C - N
~H ~ CH3 .
obtained by oxydation of the CH20H group in the latter compound ~o -the CMO group, reac-ion with o .~ (RO)2P - C~12 - C - R
; O
in which each R stands for an al~yl radical and the radica] R
bound to the C-group may also represent an optionalLy substituted ' ~ phenoxy or cycloalkyl radical, and hydrogenation of the azeto-: carbonyl yroup.
~.; Fu.rther preferred starting compounds ln the process of the :.~ invention are lactams with 5 to 13 ring members of the oxmula R - CH
~C - - N
R
: - in which R represents -(CH2)2_10, preferably -~CH2)3-, -(CH2) 4 and (CH2) 1O-~
R6 stands for hydro~Jen or a branched alkyl radical hav.ing from 3 to 10 carbon atoms with a secondary or tertiary N-~ -C
atom, preerably hydrogen.
,,, q. ~ :
.,'' . ` :
:, ~ : ; ~ : -: . . . . . . , , ,-; . :.. : ,, :.:
The compounds obtained ln this manner are also novel, they have -the :Eormula R5 - CH - oR4 I I
oD R
in which R5 and R~ have the aforesaid meaning, R4 represents an alkyl radi-cal with -I to 4 carbon atoms preferably CH3.
Com~ounds of t:his type can be used as antistatic agents in tex-tl:Le industries and as intermediates in polymerization reactions and in the preparation.o:E ~ -amino~ -dicarbo~y~lic acids according to the following reaction scheme:
` R5 - - ~ CH - OCH
3 methanolic >
mineral acid C - N
0R - :
El3COOC-E' - CH(OCEl3)2 > + HCN/NEI~HCO3 . ~ H2NR - (Strecker-Bucherer~' reaction) : .
H COOC-R5 ~ CH - CO + HCl .:
3 1 1 (acid hydrolysis) "' \ / :
C , . .
':~ o ., .
; HOOC-R -CEI~COOH
. NH2 ~ 10 -., ~ . .
, ~ . .
: ~
... , . . , .: : j, , : :. ~. ' . : , . ~ .: ~ . .; . .
. ,, ~, . . . . . .
~36~3~al Suitab].e a].cohols R~OH to carry out the process of the invent:ion are methanol, ethanol, n-propanol, isopropanol, n~
butanol5sec.-bu-tanol, preferably, however, methanol and ethanol and more preferably methanol.
The conducting salt to be used in the process of the inven-tion are alkal;. metal salts (Li, Na, K, Rb, Cs) and tetraalkyl ammoni~lm salts of tetraEluoroboric acid, hexafluorophosphori.c acid and nitric acid. They are used either singly or in admix--ture with one another. The alkyl radicals in the tetraalkyl ammonium group have 1 to 6 and preferably 1 to 4 carbon atoms, : especially the methyl and ethyl radical. The ollowi.ng conduct-~
ing salts are mentioned by way of example: :
Na-tetrafluoroborate, Na--nitrate, K--tetrafluoroborate., K-he~a-. fluorophosphate, Rb-nitrate, te-tramethylammonium tetrafluoro-'~ 15 borate, tetraethylammonium tetrafluoroborate, tetra-n-butyl-; ammonium tetrafluoroborate, -tetraethylammonium hexafluorophos~
phate, tetra-n-propylammonium hexafluorophosphate tetra-n butyl-ammonium hexafluorophosphate, or tetramethylammonium nitrate.
Preferred conducting salts are the alkali metal and tetraalkyl ~0 ammonium tetra-fluorobor~te~ especially NaBF4, KBF4 and (CH3)4-. MBF4.
I'he concentrat~on of conducting salt i.n the electrolysis solution should be ;n the range of Erom about 0~01 to about .
2.0 mol/lt preferably about 0.02 to 1.0 mol/l. The temperature of ~he electrolys~s solution should be in the range of from ~-~ about -10 to t l 00 C, preferably about 0 to 60 C.
.. : . In the electrolytic solution -the molar proportion of start-ing acid amide to alcohol is in the range oE Erom about 1:1 to 29 about 1:100, preferably 1:~ to 1:60 and more preferably 1:5 -to . '- ~ 1 ~ .
- ~ , ~OE 75/F 340 K
~ 3 1:50.
The electroc~i~emical alkoxylation accorcling to the invention may be carried out discontinuously or continuously.
The process will now be described in ~ur-ther detail by way of example only, with reference to the accompanying d~awing which is a ~iew, partly in section, of an ~lectrolysis cell suitable for carrying out the process of the invention in dis-continuous manner.
Referring to the drawing, an electrolytic cell (1) is equipped ~ith a tightly sealing cover or lid (2), through which the power supply lines for electrodes (3) and (4) are led and in which an opening (5) for the supply of the electrolysis solu-tion, an opening (6) for -the discharge of gas and a thermometer (9? are fi;~ted. The oriEice (6) for the discharge of gas may be equippeA with a reElux condenser, in which evaporating por-tiOllS of the electrolysis mixture may be recovered by conclensa-tion. The electrolytic cell (I) is encased and may be connected to a heatin~ or coolin~ llquid circuit by means of inlet and out let soc]~ets (7 and 8). The temperature of the electrolysis solu-2~ tion ~s controlled by the thermometer (9) or A thermosensor. Thetwo electrodes (3) tanode) and (4) (cathode) are set up at a ~1 distance of from 0.5 to 50 mm, preferably from 1 to 15 mm.
As electrodes there are used nets or sheets of palla~ium or platinum or noble~metal-coated metal elec-trodes, preferably titanium electrodes, mixed oxide-coated metal electrodes (as anodes), preferably titanium anodes, or graphite plates provided with slits or nOt. The use of electrode nets is especially ad-vantageous, because these facilitate the dîscharge of the gaseous 29 hydrogen formed during the electrolysis, and the uniEorm and ;
` - 12 _ .,.~ ~ ^
.' ' ' ... . . . . ' .. : '. . , . : ! ' ~ , . '~
_E75 /F 340 K
~C~6~
-thorough mixture of the electrolysis solution is additionally ~avollred by the yas current formed. The vertical disposition of the electrodes may be replaced, if desired, by a }~orizontal one. It is also possible to use several electrode pairs; a bloc~-like combination of anyular or non-angular capillary split electrodes, optional wi-th vibration oE the electrodes, has proved especially ef~icient. The so]u-tion is mixed vigorously during electrolysis by means of an agitator, for example a magnetic stirrer (10) or by circulation by pumping, especially in case of the block-like combinations.
If the process is carried out continuously, an addi-tional orifice may be set in the cover (2) of the elec-trolysis vessel for pump-circula-ting the electrolysis solution continuously.
~ portion of the electrolysis solution which is circulated by pumping is separated for work up of the product. ~fter deter-mination o~ the ratio of the desired reaction product to the starting m~terial in the electrolysis solution by the nuclear magnetic resonance spectrum or by gas chromatography t the solu-tion is worked up in known manner. The starting ma-terials, re-covered upon distillation, may be adjusted to ~he molar ratio empLoyed and then metered into the continuo1lsly reclrculating electrolysis solution together with the required quantity of the conductin~ salt or salts.
The electrolysis may be carried out under normal pressure, ~ut may be performed under reduced pressure. So as to avoid the ~ormation of explosive gas mixtures of hydrogen and air, the addition oE an inert gas, e g. nitrogen, is advantageousO
The conducting salt is suitably added aEter having prepared - 29 the alcoholic solut:Lon. However, tl-lis order may be chanyed.
- ~3 -. . - . :
- . . . ~.: ; -: : : . : ::; ~ . :
,, ., . - .. ... .. . . . . . . ..
: , : : : , . . : . . : . .
: . : : : . : . - ~ . , , . . ; ,: :
.. . . . . . ~
~IOE 75~F 3~0 K
~663~
There is no need to e~clude wa-ter strictly from the electro-lyte since mlnor amounts thereof do not affect the course oE
xeaction.
~he process gives an esp~cially high yield and is especially efficient with respect to ener~y consumed, if the conversion of cyclic carboxylic acid amide is increased, e.g. to more than 99 %, this step being also advanta~eous ~or a better work up o~ the electrolysis solution. There~ore, the electrolysis is advanta~eously continued until practically the total starting material is converted so that there is no need later to separate this from ~he the reac-tion product.
The electrolysis current is switched off after having led through the ~uantity of electricity desired, and the electroly-sis discharge is then freed from the conducting salt and worked up in knor~n manner, preEerably by dis~illa-tion. The de~ree of purity of the product may be determined by a nuclear magnetic resonance spectrum.
The current density is chosen in the range of from about 1 to 50 ~/dm , preferably 2 to 30 A/dm2. Lower current den-sities are also possible, though they diminish the rate at which the product is formed. The quantity of electricity should be about 2 to 4, preferably 2 to 3.5 and especially 2 to 3 Faradays/mol of startin~ lactam.
The ~-alkoxy derivatives of cyclic carbox~lic acid amides prepared a~cordin~ to the electrochemical process of the in~ention are valua~le intermediate produc-ts, especially for the manu~ac-ture of pharmaceuticals, having, in the first place, prosta~lan-- dine like effects and also luteolytic, bronchospasmolytic and/or 2~ antihypertensive properties and properties to inhibit the secre~
~, . . , .: . : . :
. . .. . .
: ~ ; ,: ' ' ' , '. ' :,: ' ~, . .
OE 75/F _~0 ~
~63~1~
-tion of gastrie juiee, The following e~amples illustrate the invention.
17.6 cJ of azetidinone-2- and . 5 39.6 g of methanol are electrolyzed in an electroly-tic cell havincJ a capaci-ty oE
approximately 60 ml in the presence oE 0.82 g of tetra-m-propyl-ammonium he~aEluorophosphate as conducting salt. As eleetrodes two eoncentrically placed platinum net cylinders having 225 10 mesl1es per cm2 and diameters of 1S and 30 mm, respect~vely, and a height of 50 mm are immersed in the solution~ the outer . electrode ~eing conneeted as anode. During elee-trolysis the temperature is maintained at about 10 C. After haviny switched on the el.ectrolysi.sdirect current, the current densi-ty at the anode is i ~/~m2. The eurrent i.s switehed off after passage of :~ 2.5 Faradays per mol of azetidirlone-2~ The ealeulated average . eell tension is 29.6 volts. After working up by moleeular distil-lation there are obtainecl 12.7 g of ~-methoxy-azetidinone-2 : (~oiling point ~1 C under 0.013 millibax, melting point 62 - -`:
` 2Q 63 C)~ corresponding to a material yield of 50.9 % and a eurrent .
efficieney of ~0.7 ~. :
E ~ A M P L E 2:
In an eleetrolytie eell as described in Example 1 ~` 2l.0 ~ of pyrroli~one-2 and :: 25 39.6 g of methanol are eleetr~lyzed in the presenee of 0.40 g of tetramethyl-ammonium tetrafluoroborate as eondueting salt. After having switehed on the electrolysis direet eurrent~the density at the 29 anode is 3 ~/dm2 r The eurrent i5 switehed off after the pas~ :
~ 15 ~
. ~ :
::
: : : : . . :: :. , . , : : , . :- : .
. . : . , ~ . .. ~ . , . .. : . , : .. . :
~1663~
sage o:E 2.~ Faradays per mol of pyrrolidone-2~ The calculated averacle cell tension is 35.2 volts. After working up by mole-cular distillation, 14.3 g of S-methoxypyrrolidone~2 are ob-tained (boiling poin-t 87 - 90 C under 0.14 millibar, melting poin-t 56 - 58qC~correspondi~ng to a material yield and a current eff.iciency of 50.1 ~ each.
In an electrolytic cell as described in Example 1 ~ .7 g of pyrrol:idone-2 and 10 39.5 g cf e-thanol are electxolyzed in the presence of 0.28 g of tetramethyl ammonium te-trafluoro~orate as conducting salt. After having switched on the electrolysis direct current,the anode current density is 3 A/dm2. After having passecl 2.0 Faradaysper mol o:E
lS pyrroli.done-2 -the current is switched off. The calcula-ted average .` cell tension is 48.2 volts.
: ~orking up by molecular distillat;on yields12.0 g of 5-. ethoxypyrrolidone~2 (melting point 54 - 56 C), corxesponding to a material yield and a current efficiency of 54.2 % each.
E X A M P L E 4:
~' In an electroly-tic cell as described in Example ~
~0.0 o 1~isopropyl-4-hydroxymethylpyrrolidone and 54.6 g of methanol are electroly~ed in the presence of 0.34 g of tetramethylammonium tetrafluoroborate as conducting salt. After having switched on ~ the electrolysis direct current,-the anode current density is 2 A/dmZ. ~fter the passage of 2.2 Faradays per mol of l-iso- :
propyl~4-hydroxymethylpyrrolidone,the current is switched off.
~ 29 The calculated average cell tension is 43.5 volts.
.` l~i`
- - .
, HOE 75/F 3~0 K
~06~3~0 ~:E-ter separation of the methanol and separation by columr chromatography (sllica ~el/chloroform + ethanol ~9 17) 9.0 g of 1-isopropyl--4-hydroxymethyl-5-methoxypyrrolidone-2 are obtained, corresponding to a material yield of 75.6 ~ and a current efficiency of 68.7 %.
NMR characteri~.tics of the compound:
NMR 100 millicyles per second; solvent: CDCl3; N-CH: 4.1 ppm /C~3 - N- :1.2 ppm -O-CH3- 3.3 ppm . E X A M P L E 5:
a) Preparation of 1-meth~l- and 1-isopro~vl-3- ~-carbomethoxy-2-hexiIle-y _1)7-~l-hydroxymeth~l-~yrrolidone 1-methyl com~ound ~) - 29.~ g (l38 mols) of 1-methyl--4-(2-tetrahydropyranyl-hydroxyn~ethyl)-pyrrolidone dissolved in 90 ml of diethyl ether are added ovex a peri.ocl of 20 m.Lnutes while stirring at -70~ C to 1S0 mols of LiN(i-C3H7)2 in 150 ml of diethyl ether. Stlrring is continued for 45 minutes whereupon the ~ solution is transferred to a coolable dropping funnel (-35 :: to -40 C) and added, while s-tirring over a periocl of 60 , .
.. minutes, to a solution cooled to -70 C of 29.1 g (149 mols) of 1-bromo-6-chloro-hexine(2~ in 135 ml of ether~ Stirring is continued for another 90 minutes, -the mixture is slowly .. ~ heated to room temperature, 75 ml of water a.re added drop~
; wise, the organic phase is separated ancI the aqueous phase is extracted tnree -times, each time with 50 ml of diethyl - 29 ether. The combined ether phases are washed three times .: , . .
~; - 17 ~ .
. ' , . ` .
.. - . . . . . .
`:, ''''~ ' ' '' ,' ,, ` ; ,' ~ ': ,.. : ' ' ` `', " '. ' `' , . . . . :, ~6~3~
with 40 ml each of cold sulfuric acid and once with 50 m].
of wa-ter. Af-ter drylng and concentrating under reduced pressure the organic phase, 46.6 g of crude 1-methyl-3-~6-chloro-2-hexine-yl(1)~-4-(2--tetrahydropyranyl-hydroxy-5 methyl) pyrrolidone (RF 0.42 (ethyl acetate)) are obtained The compound is used for the following reac-ti.on stage with-out further purification.
~) 7.5 y (153 mols) of sodium cyanide are dissolved in 90 ml of dimet11yl sulfoxide and the solu-tion is heated to 80 C. 46.6 g (142.5 mmols) of crude 1-methyl-3-~6-chloro-2-hexine-yl(1)~-4-(2-tetrahydropyranyl-hydroxymethyl)-pyrro-lidone dissolved in 40 ml dimethyl sulfoxide are then added dropwi.se while stirring and -the mixture is stirred for 3 to 6 hours at 80 C. The course of the reaction is followed ~y thi.l~ layer chroma-tography (e-thyl aceta-te~. When the reaction is termini~ted, the mix-ture is cooled to 10 C, 200 ml of water are added and the mixture is extracted . three times, each tlme with 200 m]. of diethyl ether. The .~ combined ether phases are washed -three times with saturated sodi.um chloride solution and dried. After concentration ~: under reduced pressure 43.7 g of crude 1-methyl-3-L6-cyano-.
- 2-hexine-yl(1)J-4-(2-tetrahydropyranyl-hydroxyme-thyl)-pyrro-. lidone ~RF 0 39 (ethyl acetate)~ are obtained, which is used ` for the next reaction without further purification.
:, 25 ~) 11 g (0.275 mol) of sodium hydroxide are di.ssolved in 33 ml of water, 43.7 g (]37.5 mols) of 1-methyl-3-~6-cyano-- . 2-hexine-yl(1)~-4-(2-tetrahydropyranyl-hydroxymethyl)-pyrro~
~ lidone dissolved in 135 ml of ethyl alcohol are added and :" 29 the whole is refluced for 18 hoursO The alcohol is removed ~ 18 -663~
under reduced pressure, 150 ml of icecold 2N sulfuric acld are aclded to the residue while cooling with ice and the whole is e~tracted ten times, each time with 100 ml of c1l-ethyl ether. After drying ~nd concentrating the combined ether phases, 47.4 g of crude 1-methyl-3-f6-carbohydroxy-2-hexine-yl)~-4-(2-tetrahydropyranyl-hydro~ymethyl)-pyrroli-done are obtalned which is direc-tly taken up in 250 ml of methylene chloride and to which 380 ml of a 0.5 molar ethereal diazomethane solution are adc1ecl a-t 0 C. The mixture is allowed to stand for 30 minutes at 0 C and for 1 hour at room temperature. After concentration under re-duced pressure~43.7 g of crude 1-methyl-3 r6-carbomethoxy-2-hexine~yl(l)~-4-(2-tetrahydropyranyl-hydroxymethyl)-pyrro-. 1idOne rRF . 45 (ethyl acetate)~ are ob-tained.
~ The product obtained is dissolved in 200 ml o metha-~` nol, 3 drops oE concentrated hydrochloric acicl are added and the mixture is refluxecl for 75 minutes. ~fter concen-~
tratil1g und~r reduced pressure~ the remainin~ oil i.5 puri-fied by column chromatography (siliea gel/ethyl acetate) 2~ to remove by-products, then ethyl acetaie:ethanol 10-1.5).
` 25 y of 1-methyl-3-/6-carbomethoxy-2-hexine-yl(1).~-4-hy-droxy~ethyl-pyrro~idone ~RF 0.14 (ethyl acetate)? are ob-~
tained.
nD = 1.5005 IR(CH Cl2): = 3450 (OH), 1740 (C=O), 1690 (C=~ cm 1 ` 2 NMR,solvent: CDCl3:N-CH3: 2~82 ppm; 0-CH3: 3.64 ppm.
1-iso~ro~l com~ound ., ~____ _ _ :.
Thls eompound is prepared in analogous manner using . ~
29 as starting compound 1-isopropyl-4-(tetrahydropyranyl-hy-. .
, . ' /
, . , . ::
. . .
- ; . ,~. ~ . ,. .: .
.
.
~166313~
dro~yme-thvl)-pyrrolidone.
nD = 1.4945 ~ CH3 NMR: solvent: CDCl3; OCH3 3.63 ppm N~ 14 ppm;
M- CH : 4.23 ppm.
b) Anoc~ic oxidatlon of the 1-isopropyl compound In an electrolytic cell having a capacity of about 60 ml 5.0 g of 1-isopropyl-3-~ -carbomethoxy-2 hexine-yl(1)J-
4-hydroxymethylpyrrolidone-2 and 57.7 g of methanol are electrolyzed ln the presence of 0.09 g of tetramethyl-; ammonium -t:etrafluoroborate as conducting salt. As electro-` des two concentrically diposed platinum net cylinders hav-ing 225 meshes per cm2 and diameters of 15 ~nd 30 ,mm, re 1S spectively, and a heigh~ of 50 mm are immersed in the solu-tion. The outer electrode is connected as anode. During electrol.ysis the temperature is maintained at about 10 C.
AEter having switched on the electrol,ysis direct current~
: the anode current ~ensity is found to be 1 A/dm2~ A~ter having passed 2.~4 Faradays per mol of starting lactam the current is switched oEf. The calculated average cell ten-sion is 31.2 volts.
After separation oE the methanol by distillation under ,~ reduced pressure there are obtained by column chromatography '" 25 (silica gel/ethyl acetate) 3.35 g of 1-isopropyl-3-/carbo-' methoxy-2-hexine-yl(~ 4-hydroxymethyl-5-methoxypyrrolidone-2 (RF 0.61; RF 0 55 (ethyl acetate~, corresponding to a ma-terial yield of 60.8 ~ an~ to a current efficiency of 50.1 29 o~ the theory.
' - 20 -., . . ' ~
', ' ' `
: . ' . ~ ' ' ' . ' :
.-~ HOE 75/F 3~0 K
~L~6~i3~
E ~ ~\ M P :[, E G-.~
In an elec-trolytic cell as clescribed in Example 1, but having a capacity o,' 400 ml 87.3 g of caprolac-tam and
AEter having switched on the electrol,ysis direct current~
: the anode current ~ensity is found to be 1 A/dm2~ A~ter having passed 2.~4 Faradays per mol of starting lactam the current is switched oEf. The calculated average cell ten-sion is 31.2 volts.
After separation oE the methanol by distillation under ,~ reduced pressure there are obtained by column chromatography '" 25 (silica gel/ethyl acetate) 3.35 g of 1-isopropyl-3-/carbo-' methoxy-2-hexine-yl(~ 4-hydroxymethyl-5-methoxypyrrolidone-2 (RF 0.61; RF 0 55 (ethyl acetate~, corresponding to a ma-terial yield of 60.8 ~ an~ to a current efficiency of 50.1 29 o~ the theory.
' - 20 -., . . ' ~
', ' ' `
: . ' . ~ ' ' ' . ' :
.-~ HOE 75/F 3~0 K
~L~6~i3~
E ~ ~\ M P :[, E G-.~
In an elec-trolytic cell as clescribed in Example 1, but having a capacity o,' 400 ml 87.3 g of caprolac-tam and
5 247.1 g oE me-thanol are electrolyzed in the presence of 1.24 g of tetramethylammonium tetrafluorobora-te as conducting salt. The platinum net cylinders have a height oi 100 mm. After having switched on -the electro-. lysis d.irect current, the anode current dens.ity is found -to be 10 3 A/dm2. After having passed 3.0 Faraclays per mole of ~-capro-~ lactam~the current is swi-tched off. The calculated ave.rage cell :;. tension is 26.8 volts.
After working up by molecular distillat-on,61.1 g of .~ -methoxy-caprolactam (boiling point 106 - 108~ C under 0.6 millibar; melting point 65 ~ 66 C~ are obtained, corresponding .. to a material yield of 55.3 ~ and a current efficienc~ of 36l9 %.
E X A M P L E 7: .
In an electrolytic cell as described in Example 6 87.3 cJ of caprolactam and 20 ~ 247.1 g of methanol are electrolyzed in the presence of 9.7 g of potassium tetra-fluoroborate as conducting salt. After having switched on the ..
electrolysis direct current, the anode current density is ~` 1 A/dm2. The current is switched off after passage of 3O0 ~. . . .
Faradays per mol of ~-caprolactam. The calculated average cell tension is 30.3 volts.
After worki.ng up ~y molecular distillation, 59.0 g o ~-methoxy-caprolactam ~boiling point 106 - 108 C under 0~6 29 millibar; melting poi.nt 65 66 C~ are obtained, corresponding - 2~ -'' . ` ' . ' ~ ' '` ' . ' ,' , ' , ' ' . ' ~': " " ' ' .' to a material vlelcl of 53.~ ~ and a current efficiency oE 35.6 ~.
E X ~ M P L ~ 8:
In an electrolytic cell as described in Example 6 78.6 g of piperidone-2 and 253.9 g of methanol are electrol~zed in the presence of 1.28 g of -te-trame-thylammonium -tetrafluoroborate as concluc-ting sal-t. Af-ter having switched on - -the electroL~sis direc-t current, the anode current densi-ty is found to be 2 A/dm2. After passage of 2.4 Faradays pe.r mol of p:iperidone-2, -the curren-t is swi-tched off. The calculated average cell tension is 1?.4 vol-tsO
After removal of the methanol and twofold recrystallization :~ in di-isopropyl ~ther, 73.4 g of 6-methoxypiperidone-2 (melting point 110 - 111 C) are ob-tained, corresponding to a ma-teri.al - ~-; 15 yield of 71.1 % and a curren-t efficiency of 59.2 ~.
E X A M _ L E 9:
In an elec-troly-tic cell as described in Example 6 8~.3 g of ~-caprolactam and 247.1 ~ of methanol are electrolyzed in -the presence o~ 8.4 g of sodium tetrafluoro-borate as conducting salt. After having switched on the elec-tro-lysis direct current, the anode current density is found to ~e 3 A/dm2. After passage ~f 3~0 Faradays per mol of ~-caprolac--tam the current is disconnec-ted. The average cell tension is calculated to be 12.9 volts. ~fter working up by molecular distillation, 80~0 g o~ ~-methoxy--~-caprolactam are obtained, corresponding to a material yield of 72.4 % and a current effi-~` ciency of 48.3 ~.
., - . . .
. : . . . ~ . , l ~iOE 75/F 3~10 K
.
E X A M P 1. E. 10:
A test is carried out under the conditions of Example 9 ~/ith -the e~ception, however, tha-t a mix-ture of 4.2 g of sodium - -tetra:Eluoroborate and 5.9 g of tetramethylammonium tetra-Eluoro-.: 5 borate is used as conducting saltO Af-ter disconnection of the ,~ current, -the average cell -tension is calculated to be 18.7 volts.
By working up by molecular distilla-tion 78.~1 g of ~methoxy- -caprolactam are obtained, corresponding -to a ma-terial yield of 71.0 % and to a current efficiency of ~7.3 %.
E X A M P L E 11:
In an electroly-tic cell as described in Example 6 72.24 g of laurinolactam and ~;~ 293.33 y oE met11anol -are electrolyzed in the presence of 0.6 ~ of tetramethylammonium . 15 tetrafluoroborate as conducting salt. After having switched on .. the electrolysis direct current, the anode current density is found to be 2 A/dm?. A~ter havln~ passed 3.5 Faradays per mol o~ laurinolactam~the current is disconnected, I'he calculated .
avera~e cell tension is 4~.1 volts.
After working up and recrystallixation ~2.4 g of ~ metho~Yy-~` laurinolactam of the formula . . -~ . .
~` ' . . ....
. ~ 2 10 ~
~ O=C CHOCH3 : . ~ N
. H
(meltin~ point 153.5 - 154.5C) are obtained, corresponding to ` a material yield of 50.9 ~ and a current effi.ciency of 29.1 ~.
. . ~
- 23 - ~
HOE 75/~ 340 K
63~3~
E X A l~l P L E 12-In an electrolytic cell as described in Example 1 16.7 g of caprolactam and 75.8 ~ of me-thanol are electrolyzed in the presence of 0.19 g of tetramethylammonium tetra:Eluoroborate as conducting salt. After having switched on the electrolysis direct current, the anode current density is 1 A/dm2. The current is disconnected after having passed 3.0 Faradays per mol of caprylolactamO The calculated average cell tensi~n is 35.2 volts.
After working up by molecular di~-tilla-tion 11.6 g of -metho~ycaprylolactam of the formula .
, .
)6 ~ nD = 1.~980 O-C OII OCI-I3 (boiling point 55 C under . ~I 0.013 millibar : .
~ are o~tained, cor.responding to a ma-terial yield o~ 57.2 % and '~ a current eEficiency of 38.3 %.
?:~ . .
, - ' ' '` ' . ~ . .
., .
' ,s, ~
, :" .
;
~ 24 _ : ~
;,, . , . ~:
After working up by molecular distillat-on,61.1 g of .~ -methoxy-caprolactam (boiling point 106 - 108~ C under 0.6 millibar; melting point 65 ~ 66 C~ are obtained, corresponding .. to a material yield of 55.3 ~ and a current efficienc~ of 36l9 %.
E X A M P L E 7: .
In an electrolytic cell as described in Example 6 87.3 cJ of caprolactam and 20 ~ 247.1 g of methanol are electrolyzed in the presence of 9.7 g of potassium tetra-fluoroborate as conducting salt. After having switched on the ..
electrolysis direct current, the anode current density is ~` 1 A/dm2. The current is switched off after passage of 3O0 ~. . . .
Faradays per mol of ~-caprolactam. The calculated average cell tension is 30.3 volts.
After worki.ng up ~y molecular distillation, 59.0 g o ~-methoxy-caprolactam ~boiling point 106 - 108 C under 0~6 29 millibar; melting poi.nt 65 66 C~ are obtained, corresponding - 2~ -'' . ` ' . ' ~ ' '` ' . ' ,' , ' , ' ' . ' ~': " " ' ' .' to a material vlelcl of 53.~ ~ and a current efficiency oE 35.6 ~.
E X ~ M P L ~ 8:
In an electrolytic cell as described in Example 6 78.6 g of piperidone-2 and 253.9 g of methanol are electrol~zed in the presence of 1.28 g of -te-trame-thylammonium -tetrafluoroborate as concluc-ting sal-t. Af-ter having switched on - -the electroL~sis direc-t current, the anode current densi-ty is found to be 2 A/dm2. After passage of 2.4 Faradays pe.r mol of p:iperidone-2, -the curren-t is swi-tched off. The calculated average cell tension is 1?.4 vol-tsO
After removal of the methanol and twofold recrystallization :~ in di-isopropyl ~ther, 73.4 g of 6-methoxypiperidone-2 (melting point 110 - 111 C) are ob-tained, corresponding to a ma-teri.al - ~-; 15 yield of 71.1 % and a curren-t efficiency of 59.2 ~.
E X A M _ L E 9:
In an elec-troly-tic cell as described in Example 6 8~.3 g of ~-caprolactam and 247.1 ~ of methanol are electrolyzed in -the presence o~ 8.4 g of sodium tetrafluoro-borate as conducting salt. After having switched on the elec-tro-lysis direct current, the anode current density is found to ~e 3 A/dm2. After passage ~f 3~0 Faradays per mol of ~-caprolac--tam the current is disconnec-ted. The average cell tension is calculated to be 12.9 volts. ~fter working up by molecular distillation, 80~0 g o~ ~-methoxy--~-caprolactam are obtained, corresponding to a material yield of 72.4 % and a current effi-~` ciency of 48.3 ~.
., - . . .
. : . . . ~ . , l ~iOE 75/F 3~10 K
.
E X A M P 1. E. 10:
A test is carried out under the conditions of Example 9 ~/ith -the e~ception, however, tha-t a mix-ture of 4.2 g of sodium - -tetra:Eluoroborate and 5.9 g of tetramethylammonium tetra-Eluoro-.: 5 borate is used as conducting saltO Af-ter disconnection of the ,~ current, -the average cell -tension is calculated to be 18.7 volts.
By working up by molecular distilla-tion 78.~1 g of ~methoxy- -caprolactam are obtained, corresponding -to a ma-terial yield of 71.0 % and to a current efficiency of ~7.3 %.
E X A M P L E 11:
In an electroly-tic cell as described in Example 6 72.24 g of laurinolactam and ~;~ 293.33 y oE met11anol -are electrolyzed in the presence of 0.6 ~ of tetramethylammonium . 15 tetrafluoroborate as conducting salt. After having switched on .. the electrolysis direct current, the anode current density is found to be 2 A/dm?. A~ter havln~ passed 3.5 Faradays per mol o~ laurinolactam~the current is disconnected, I'he calculated .
avera~e cell tension is 4~.1 volts.
After working up and recrystallixation ~2.4 g of ~ metho~Yy-~` laurinolactam of the formula . . -~ . .
~` ' . . ....
. ~ 2 10 ~
~ O=C CHOCH3 : . ~ N
. H
(meltin~ point 153.5 - 154.5C) are obtained, corresponding to ` a material yield of 50.9 ~ and a current effi.ciency of 29.1 ~.
. . ~
- 23 - ~
HOE 75/~ 340 K
63~3~
E X A l~l P L E 12-In an electrolytic cell as described in Example 1 16.7 g of caprolactam and 75.8 ~ of me-thanol are electrolyzed in the presence of 0.19 g of tetramethylammonium tetra:Eluoroborate as conducting salt. After having switched on the electrolysis direct current, the anode current density is 1 A/dm2. The current is disconnected after having passed 3.0 Faradays per mol of caprylolactamO The calculated average cell tensi~n is 35.2 volts.
After working up by molecular di~-tilla-tion 11.6 g of -metho~ycaprylolactam of the formula .
, .
)6 ~ nD = 1.~980 O-C OII OCI-I3 (boiling point 55 C under . ~I 0.013 millibar : .
~ are o~tained, cor.responding to a ma-terial yield o~ 57.2 % and '~ a current eEficiency of 38.3 %.
?:~ . .
, - ' ' '` ' . ~ . .
., .
' ,s, ~
, :" .
;
~ 24 _ : ~
;,, . , . ~:
Claims (15)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A process for the preparation of a compound of the formula I
I
wherein R4 represents an alkyl radical having from 1 to 4 carbon atoms, R5 represents a linear or branched alkylene radical having from 1 to 10 carbon atoms in the chain which may be substituted by groups which are not reactive under the reaction conditions, R6 represents hydrogen or a branched alkyl radical having from 3 to 10 carbon atoms with a secondary or tertiary N-.alpha.-C-atom, in which an N-carboxylic acid amide which is a lactam of the formula wherein R5 and R6 are as defined above, is subjected to an anodic alkoxylation in the presence of an alcohol of the formula R4OH wherein R4 is as defined above, in the presence of at least one alkali metal or tetraalkylammonium tetra-fluoroborate, hexafluorophosphate or nitrate as conducting salt, at a temperature of up to about 100°C in an electrolytic cell with a stationary or flowing electrolyte.
I
wherein R4 represents an alkyl radical having from 1 to 4 carbon atoms, R5 represents a linear or branched alkylene radical having from 1 to 10 carbon atoms in the chain which may be substituted by groups which are not reactive under the reaction conditions, R6 represents hydrogen or a branched alkyl radical having from 3 to 10 carbon atoms with a secondary or tertiary N-.alpha.-C-atom, in which an N-carboxylic acid amide which is a lactam of the formula wherein R5 and R6 are as defined above, is subjected to an anodic alkoxylation in the presence of an alcohol of the formula R4OH wherein R4 is as defined above, in the presence of at least one alkali metal or tetraalkylammonium tetra-fluoroborate, hexafluorophosphate or nitrate as conducting salt, at a temperature of up to about 100°C in an electrolytic cell with a stationary or flowing electrolyte.
2. A process as claimed in claim 1 in which about 2 to 3.5 Faradays are used per mol of starting lactam.
3. A process as claimed in claim 1 in which the con-ducting salt is an alkaline metal or tetraalkylammonium tetrafluoroborate or a mixture thereof.
4. A process as claimed in claim 1 wherein the con-ducting salt is NaBF4, KBF4 and (CH3)4NBF4.
5. A process as claimed in claim 1 in which the con-centration of conducting salt is about 0.01 to 2.0 mol per liter.
6. A process as claimed in claim 1 in which the temperature is in the range of from 0 to 60°C.
7. A process as claimed in claim 1 in which the molar proportion of starting lactam to alcohol is about 1:1 to 1:100.
8. A process for the preparation of a compound of the formula Ia wherein R4 represents an alkyl radical having from 1 to 4 carbon atoms; R5 represents -(CH2)2-10- and R6 represents a branched (C3-C10)-alkyl radical with a secondary or tertiary N-.alpha.-C-atom and, when R represents -(CH2)4-10-, R6 may also represent hydrogen, in which an N-carboxylic acid amide which is a lactam of the formula wherein R5 and R6 are as defined above, is subjected to an anodic alkoxylation in the presence of an alcohol of the formula R4OH wherein R4 is as defined above in the presence of at least one alkali metal or tetraalkylammonium tetrafluoroborate, hexafluorophosphate or nitrate as conducting salt, at a temperature of up to about 100°C
in an electrolytic cell with a stationary or flowing electro-lyte.
in an electrolytic cell with a stationary or flowing electro-lyte.
9. A compound of the formula Ia as defined in claim 8 whenever obtained according to a process as claimed in claim 8 or by an obvious chemical equivalent thereof.
10. A process as claimed in claim 8 for the preparation of a compound of the formula Ia as defined in claim 8 wherein R4 represents (C1-C4)-alkyl, R5 represents -(CH2)4-10- and R6 represents hydrogen.
11. A composition of the formula Ia as defined in claim 10, whenever obtained according to a process as claimed in claim 10 or by an obvious chemical equivalent thereof.
12. A process as claimed in claim 1 for the preparation of a compound of the formula II
II
wherein R4 represents an alkyl radical having 1to 4 carbon atoms, wherein a correspondingly substituted lactam is reacted with an alcohol of the formula R4OH wherein R4 is as defined above.
II
wherein R4 represents an alkyl radical having 1to 4 carbon atoms, wherein a correspondingly substituted lactam is reacted with an alcohol of the formula R4OH wherein R4 is as defined above.
13. A process as claimed in claim 1 for a compound of the formula III
III
wherein R4 and R6 are as defined in claim 1 and A represents -C?C-, -CH=CH- or -CH2-CH2- and R7 represents an alkyl radical having from 1 to 4 carbon atoms, a cycloalkyl radical having 5 or 6 carbon atoms or an araliphatic radical, in which a correspondingly substituted lactam is reacted with an alcohol of the formula R4OH wherein R4 is as defined in claim 1.
III
wherein R4 and R6 are as defined in claim 1 and A represents -C?C-, -CH=CH- or -CH2-CH2- and R7 represents an alkyl radical having from 1 to 4 carbon atoms, a cycloalkyl radical having 5 or 6 carbon atoms or an araliphatic radical, in which a correspondingly substituted lactam is reacted with an alcohol of the formula R4OH wherein R4 is as defined in claim 1.
14. A process as claimed in claim 1 for the preparation of a compound of the formula IV
IV
wherein A represents -C?C-, R4 and R7 represent CH3 and R6 represents in which a correspondingly substituted lactam is reacted with CH3OH.
IV
wherein A represents -C?C-, R4 and R7 represent CH3 and R6 represents in which a correspondingly substituted lactam is reacted with CH3OH.
15. A process as claimed in claim 1 for the preparation of a compound of the formula I wherein R4 represents CH3, R5 represents -(CH2)3-, -(CH2)4- or -(CH2)10- and R6 represents hydrogen, in which a correspondingly substituted lactam is reacted with CH3OH.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19752557765 DE2557765A1 (en) | 1975-12-20 | 1975-12-20 | OMEGA ALCOXY DERIVATIVES OF LACTAMEN AND THE PROCESS FOR THE PREPARATION |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1066300A true CA1066300A (en) | 1979-11-13 |
Family
ID=5965143
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA268,144A Expired CA1066300A (en) | 1975-12-20 | 1976-12-17 | .omega.-ALKOXY DERIVATIVES OF LACTAMS AND PROCESS FOR THEIR MANUFACTURE |
Country Status (10)
| Country | Link |
|---|---|
| JP (1) | JPS5278865A (en) |
| AT (1) | AT349027B (en) |
| AU (1) | AU505404B2 (en) |
| BE (1) | BE849625A (en) |
| CA (1) | CA1066300A (en) |
| DE (1) | DE2557765A1 (en) |
| FR (1) | FR2335621A1 (en) |
| GB (1) | GB1571900A (en) |
| IT (1) | IT1065685B (en) |
| NL (1) | NL7613921A (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FI943962A (en) | 1993-08-30 | 1995-03-01 | Mcneil Ppc Inc | Improved absorbent nonwovens |
| CN113073346B (en) * | 2020-01-06 | 2022-04-22 | 万华化学集团股份有限公司 | Electrochemical method for simultaneously preparing o-diol and pyrrole methoxylation products |
-
1975
- 1975-12-20 DE DE19752557765 patent/DE2557765A1/en not_active Withdrawn
-
1976
- 1976-12-15 NL NL7613921A patent/NL7613921A/en not_active Application Discontinuation
- 1976-12-17 AU AU20703/76A patent/AU505404B2/en not_active Expired
- 1976-12-17 IT IT30584/76A patent/IT1065685B/en active
- 1976-12-17 CA CA268,144A patent/CA1066300A/en not_active Expired
- 1976-12-17 AT AT936476A patent/AT349027B/en not_active IP Right Cessation
- 1976-12-20 BE BE173446A patent/BE849625A/en unknown
- 1976-12-20 FR FR7638401A patent/FR2335621A1/en active Granted
- 1976-12-20 JP JP51152144A patent/JPS5278865A/en active Pending
- 1976-12-20 GB GB53126/76A patent/GB1571900A/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| ATA936476A (en) | 1978-08-15 |
| BE849625A (en) | 1977-06-20 |
| AU505404B2 (en) | 1979-11-22 |
| JPS5278865A (en) | 1977-07-02 |
| DE2557765A1 (en) | 1977-06-23 |
| FR2335621A1 (en) | 1977-07-15 |
| FR2335621B3 (en) | 1979-08-31 |
| IT1065685B (en) | 1985-03-04 |
| GB1571900A (en) | 1980-07-23 |
| AU2070376A (en) | 1978-06-22 |
| AT349027B (en) | 1979-03-12 |
| NL7613921A (en) | 1977-06-22 |
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