DK165113B - N-(Alkoxyalkyl)-2,4-dialkyltetrahydrothien-3-ylideneimine derivatives, and process for preparing N-(2,4- dialkylthien-3-yl)-N-(alkoxyalkyl)chloroacetamide derivatives using the N-(alkoxyalkyl)-2,4- dialkyltetrahydrothien-3-ylideneimine derivatives - Google Patents
N-(Alkoxyalkyl)-2,4-dialkyltetrahydrothien-3-ylideneimine derivatives, and process for preparing N-(2,4- dialkylthien-3-yl)-N-(alkoxyalkyl)chloroacetamide derivatives using the N-(alkoxyalkyl)-2,4- dialkyltetrahydrothien-3-ylideneimine derivatives Download PDFInfo
- Publication number
- DK165113B DK165113B DK344785A DK344785A DK165113B DK 165113 B DK165113 B DK 165113B DK 344785 A DK344785 A DK 344785A DK 344785 A DK344785 A DK 344785A DK 165113 B DK165113 B DK 165113B
- Authority
- DK
- Denmark
- Prior art keywords
- alkoxyalkyl
- formula
- derivatives
- compounds
- dialkyltetrahydrothien
- Prior art date
Links
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Plural Heterocyclic Compounds (AREA)
Description
iin
DK 165113BDK 165113B
Den foreliggende opfindelse angår hidtil ukendte N-(alkoxy-alkyl)-2,4-dialkyltetrahydrothien-3-ylideniminderivater og en fremgangsmåde til fremstilling af N-(2,4-dialkylthien-3-yl)-N-(alkoxyalkyl)chloracetamidderivater under anvendelse 5 af N-(alkoxyalkyl)-2,4-dialkyltetrahydrothien-3-ylidenimin-derivaterne.The present invention relates to novel N- (alkoxyalkyl) -2,4-dialkyltetrahydrothien-3-ylidenimine derivatives and a process for the preparation of N- (2,4-dialkylthien-3-yl) -N- (alkoxyalkyl) chloroacetamide derivatives using 5 of the N- (alkoxyalkyl) -2,4-dialkyltetrahydrothien-3-ylidenimine derivatives.
Mere specifikt angår den foreliggende opfindelse hidtil ukendte tetrahydrothiopheniminer med den almene formel IMore specifically, the present invention relates to novel tetrahydrothiophenimines of general formula I
R.y. .........^NRR. Y. ......... ^ NR
10 * I I10 * I I
^ s ^r2 hvor R betegner C-^-alkoxy-^^-alkyl, hvor C^,^- alkoxygruppen med mindst 2 carbonatomer er adskilt fra det N-atom, hvortil R er bundet, 15 og hvert af symbolerne R2 og R4 uafhængigt af hinanden betegner CH3 eller C2H5.2 is R 2 where R represents C 1-4 alkoxy- 4 alkyl, wherein the C 1-6 alkoxy group having at least 2 carbon atoms is separated from the N atom to which R is attached, and each of the symbols R2 and R4 independently of each other denotes CH3 or C2H5.
Det har vist sig, at forbindelser med formlen I let kan de-20 hydrogeneres til dannelse af forbindelser med den almene formel IIIt has been found that compounds of formula I can be readily dehydrogenated to form compounds of general formula II
V,_. nh-r 25 hvor R, R2 og R4 har den ovenfor anførte betydning.V, _. nh-r 25 wherein R, R 2 and R 4 have the meaning given above.
Forbindelser med formlen II er kendte mellemprodukter til fremstilling af forbindelser med den almene formel IIICompounds of formula II are known intermediates for the preparation of compounds of general formula III
22
DK 165113BDK 165113B
R4|—/ V C0-CH2C1 IIIR4 | - / V C0-CH2C1 III
S l^2 hvor R, R2 og R4 har den ovenfor anførte betydning.S 1 2 where R, R 2 and R 4 have the meaning given above.
5 Forbindelser med formlen III er kendte herbicider.Compounds of formula III are known herbicides.
Opfindelsen angår også en fremgangsmåde til fremstilling af et N-(2,4-dialkylthien-3-yl)-N-(alkoxyalkyl)chloracetamid-derivat med den almene formel IIIThe invention also relates to a process for the preparation of an N- (2,4-dialkylthien-3-yl) -N- (alkoxyalkyl) chloroacetamide derivative of the general formula III
10 R4Tj-j/ N<^C0-CH2C1 111R4Tj-j / N <^ C0-CH2 Cl1 111
hvor R, R2 og R4 har den ovenfor anførte betydning, hvilken fremgangsmåde er ejendommelig ved, at en forbindelse med formlen I ved hjælp af thionylchlorid dehydrogeneres til 15 dannelse af en forbindelse med formlen IIwherein R, R 2 and R 4 are as defined above, which is characterized in that a compound of formula I is dehydrogenated by thionyl chloride to form a compound of formula II
R. . NH-RR.. NH-R
TXTX
S^r2 hvor R, R2 og R4 har den ovenfor anførte betydning, og den 20 således vundne forbindelse med formlen II N-chloracetyle-res.Wherein R, R 2 and R 4 are as defined above and the compound thus obtained of formula II is N-chloroacetylated.
Forbindelser II og III er beskrevet i britisk patentskrift nr. 2.114.566A. I dette patentskrift er der angivet flere fremgangsmåder til fremstilling af forbindelser med formlen 25 III, men ingen af de der beskrevne fremgangsmåder eller andre i litteraturen beskrevne fremgangsmåder muliggørCompounds II and III are described in British Patent Specification No. 2,144,566A. This patent discloses several processes for preparing compounds of formula 25 III, but none of the methods described or other methods described in the literature allow
DK 165113 BDK 165113 B
3 fremstilling af forbindelserne med formlen III ud fra let tilgængelige udgangsmaterialer.3 preparing the compounds of formula III from readily available starting materials.
Med den foreliggende opfindelse er der tilvejebragt en meget bekvem vej til fremstilling af forbindelser med 5 formlen III.With the present invention there is provided a very convenient way of preparing compounds of formula III.
Det var overraskende, at thionylchlorid kan anvendes som oxidationsmiddel for 2-iminotetrahydrothiophen-forbindel-ser, og at oxidationsreaktionen giver højt udbytte af 3-aminothiophenforbindelser. Denne reaktion forløber hurtigt 10 ved lave temperaturer (stuetemperaturer), og ingen yderligere uønsket oxidation til fx thiophen observeres.Surprisingly, thionyl chloride can be used as the oxidizing agent for 2-iminotetrahydrothiophene compounds and that the oxidation reaction gives high yield of 3-aminothiophene compounds. This reaction proceeds rapidly at low temperatures (room temperatures) and no further undesired oxidation to, for example, thiophene is observed.
Thionylchlorid er i den organiske kemi hovedsagelig anvendt til substitution af hydroxygrupper med chlorid, men en sådan reaktion er ikke en oxidation.Thionyl chloride is used in organic chemistry mainly for the substitution of hydroxy groups with chloride, but such a reaction is not an oxidation.
15 I sjældne tilfælde, nemlig i forbindelse med C-H-sure forbindelser som malonsyreester, er substitution af det sure H bundet til C-atomet observeret.In rare cases, namely in connection with C-H acidic compounds such as malonic acid ester, substitution of the acidic H bonded to the C atom has been observed.
Kun få referencer omfatter anvendelsen af thionylchlorid som oxidationsmiddel. I en artikel fra JACS (1964, vol. 86, 20 s. 5654-5658) beskrives omsætning af 3-acetyl-4-hydroxy-5-(S-benzylthio)methyl-3-pyrrolidin-2-on med thionylchlorid under dannelse af 3-acetyl-4-hydroxy-5-(S-benzylthio)methy-len-3-pyrrolin-2-on. Det fremgår af artiklen, at 1) reaktionen var uventet, 25 2) dehydrogenering af sekundære amider ved hjælp af thio nylchlorid var ukendt, 3) den tilsvarende N-methyl-substituerede lactam kunne ikke dehydrogeneres med thionylchlorid, og 4) litteraturen beskriver kun meget få omdannelse, hvor 30 dette reagens virker som oxidationsmiddel.Only a few references include the use of thionyl chloride as the oxidizing agent. In an article from JACS (1964, vol. 86, 20 pp. 5654-5658), the reaction of 3-acetyl-4-hydroxy-5- (S-benzylthio) methyl-3-pyrrolidin-2-one with thionyl chloride to form of 3-acetyl-4-hydroxy-5- (S-benzylthio) methylene-3-pyrrolin-2-one. It appears from the article that 1) the reaction was unexpected, 2) the dehydrogenation of secondary amides by thio nyl chloride was unknown, 3) the corresponding N-methyl-substituted lactam could not be dehydrogenated with thionyl chloride, and 4) the literature describes very little get a conversion where this reagent acts as an oxidizing agent.
DK 165113 BDK 165113 B
44
De øvrige kendte referencer, som beskriver anvendelsen af thionylchlorid som oxidationsmiddel, angår oxidation af pyridin til N-pyridyl-(4)-pyridiniumchlorid og oxidation af benzoin til benzil. I alle disse reaktioner er udgangsmate-5 rialerne fuldstændig forskellige fra de udgangsmaterialer, der anvendes ved fremgangsmåden ifølge den foreliggende opfindelse. Thionylchlorid kan derfor ikke betragtes som et klassisk oxidationsmiddel, og det var uventet, at behandlingen af 3-iminotetrahydrothiophenforbindelserne med 10 formlen I ifølge opfindelsen ville give 3-aminothiophenfor-bindelser med formlen II, endsige at der opnås et så højt udbytte: i eksempel 2 opnås et udbytte på 75%, mens der i eksempel 5a opnås et udbytte på 82%.The other known references describing the use of thionyl chloride as the oxidizing agent relate to oxidation of pyridine to N-pyridyl- (4) -pyridinium chloride and oxidation of benzoin to benzil. In all these reactions, the starting materials are completely different from the starting materials used in the process of the present invention. Therefore, thionyl chloride cannot be considered a classic oxidizer, and it was unexpected that the treatment of the 3-iminotetrahydrothiophene compounds of formula I of the invention would yield 3-aminothiophene compounds of formula II, let alone achieve such a high yield: in Example 2 a yield of 75% is obtained, while in example 5a a yield of 82% is obtained.
Behandlingen med thionylchlorid foretages bekvemt i et 15 opløsningsmiddel, som er inert under reaktionsbetingelserne. Eksempler på egnede opløsningsmidler er chlorerede carbonhydrider, fx CEtøC^, og carbonhydrider såsom toluen eller cyclohexan. Reaktionstemperaturen ligger bekvemt i området mellem -30 og +80° C, fx ved stuetemperatur (ca. 20-20 30°C) .The treatment with thionyl chloride is conveniently carried out in a solvent which is inert under the reaction conditions. Examples of suitable solvents are chlorinated hydrocarbons, for example CEtOC 2, and hydrocarbons such as toluene or cyclohexane. The reaction temperature is conveniently in the range between -30 and + 80 ° C, for example at room temperature (about 20-20 30 ° C).
Thionylchlorid er overraskende velegnet til anvendelse som oxidationsmiddel ved denne reaktion: Reaktionen kan udføres under milde reaktionsbetingelser, og der iagttages ikke uønskede bireaktioner (fx chlorering, yderligere oxidation, 25 etc.).Thionyl chloride is surprisingly suitable for use as an oxidizing agent in this reaction: The reaction can be carried out under mild reaction conditions and undesirable side reactions (e.g. chlorination, further oxidation, etc.) are observed.
De således vundne forbindelser med formlen II omdannes til forbindelser med formlen III ved N-chloracetylering. Denne N-chloracetylering kan udføres ved fremgangsmåder, der er kendte til fremstilling af chloracetamider ud fra tilsva-30 rende aminer, fx under de i britisk patentskrift nr.The compounds of formula II thus obtained are converted to compounds of formula III by N-chloroacetylation. This N-chloroacetylation can be carried out by methods known for the preparation of chloroacetamides from the corresponding amines, for example under those of British Pat.
2.114.456A beskrevne betingelser.2.114.456A conditions described.
Når forbindelserne med formlen I oxideres ved hjælp af thionylchlorid, fås forbindelserne med formlen II i form af hydrochlorid-syreadditionssaltet. Dette hydrochlorid kanWhen the compounds of formula I are oxidized by thionyl chloride, the compounds of formula II are obtained in the form of the hydrochloride acid addition salt. This hydrochloride can
DK 165113 BDK 165113 B
5 omsættes med chloracetylchlorid uden forudgående isolering fra reaktionsblandingen og i fravær af en base, hvorved der fås praktisk taget kvantitative udbytter af forbindelser med formlen III.5 is reacted with chloroacetyl chloride without prior isolation from the reaction mixture and in the absence of a base to give practically quantitative yields of compounds of formula III.
5 Forbindelserne med formlen I fås let ud fra de tilsvarende tetrahydrothiophen-3-oner med den almene formel IVThe compounds of formula I are readily obtained from the corresponding tetrahydrothiophen-3-ones of general formula IV
HH
10 hvor R2 og R4 har den ovenfor anførte betydning, ved omsætning med en amin med den almene formel VWherein R 2 and R 4 are as defined above by reaction with an amine of the general formula V
H2N-R VH2N-R V
hvor R har den ovenfor anførte betydning.where R has the meaning given above.
En sådan kondensationsreaktion udføres bekvemt i et opløs-15 ningsmiddel, som er inert under reaktionsbetingelserne, fx cyclohexan eller toluen. Reaktionen foretages fortrinsvis under opvarmning, fx til tilbagesvalingstemperatur. Reaktionsproduktet tørres hensigtsmæssigt, fx ved hjælp af en vandfælde eller med en egnet molekylsi, fx på 5 Å. Dette 20 kan foretages kontinuerligt ved anvendelse af en køler, fx en vandkøler, og dirigering af kondensatet gennem en kolonne, der omfatter en molekylsi, som fortrinsvis er beskyttet med N2 for at udelukke atmosfærisk oxygen.Such a condensation reaction is conveniently carried out in a solvent which is inert under the reaction conditions, for example cyclohexane or toluene. The reaction is preferably carried out under heating, for example to reflux temperature. The reaction product is suitably dried, for example by means of a water trap or with a suitable molecular sieve, for example 5 Å. This can be done continuously using a cooler, eg a water cooler, and routing the condensate through a column comprising a molecular sieve which is preferably protected with N 2 to exclude atmospheric oxygen.
Den ovenfor beskrevne reaktionsvej til fremstilling af for-25 bindeiser med formlen III ud fra forbindelser med formlen IV - via forbindelser med formlerne I og II kan foretages i samme reaktionsbeholder, dvs., at forbindelser med formlerne I og II kan fås i gode udbytter og ikke behøver at blive isoleret fra reaktionsbeholderen til næste reaktionstrin.The reaction pathway described above for the preparation of compounds of formula III from compounds of formula IV - via compounds of formulas I and II can be made in the same reaction vessel, i.e., compounds of formulas I and II can be obtained in good yields and does not need to be isolated from the reaction vessel for the next reaction step.
66
DK 165113BDK 165113B
Forbindelser med formlen IV er hidtil ukendte. De dannes let ved cyclisering af forbindelser med den almene formel VICompounds of formula IV are novel. They are readily formed by cyclizing compounds of general formula VI
HO-CO-CH(R2)-S-CH2-CH(R4)COOH VIHO-CO-CH (R2) -S-CH2-CH (R4) COOH VI
5 hvor R2 og R4 har den ovenfor anførte betydning.5 wherein R 2 and R 4 are as defined above.
En sådan cyclisering kan udføres under Ruzicka-cycliseringsbetingelser eller modifikationer deraf.Such cyclization can be performed under Ruzicka cyclization conditions or modifications thereof.
Cycliseringen foretages bekvemt under opvarmning; forekomsten af et kondensationsmiddel, fx Ba(OH)2, MnC03, jernpul-10 ver, acetater af Fe, Co(II) eller Ni(II), eddikesyre-anhydrid/LiCl eller en tertiær amin såsom trialkylamin, fremskynder cyclisering. Anvendelsen af jernpulver eller acetater af Fe, Co(II) eller Ni(II) som kondensationsmiddel er særlig fordelagtig.The cyclization is conveniently carried out under heating; the presence of a condensing agent, e.g., Ba (OH) 2, MnCO3, iron powder, acetates of Fe, Co (II) or Ni (II), acetic anhydride / LiCl or a tertiary amine such as trialkylamine, accelerates cyclization. The use of iron powder or acetates of Fe, Co (II) or Ni (II) as a condensing agent is particularly advantageous.
15 Udtrykket "acetater af Fe" angiver i nærværende beskrivelse Fe(II)-og Fe(III)-acetatforbindelser såsom Fe(acetat)2 og Fe(OH)2(acetat).The term "acetates of Fe" herein refers to Fe (II) and Fe (III) acetate compounds such as Fe (acetate) 2 and Fe (OH) 2 (acetate).
Forbindelser med formlen VI er også hidtil ukendte. De kan dannes ud fra let tilgængelige udgangsmaterialer ved addi-20 tion af en forbindelse med den almene formel VIICompounds of formula VI are also novel. They can be formed from readily available starting materials by the addition of a compound of general formula VII
HO-CO-CH(R2)-SH VIIHO-CO-CH (R2) -SH VII
hvor R2 har den ovenfor anførte betydning, til en forbindelse med den almene formel VIIIwherein R 2 is as defined above for a compound of general formula VIII
CH2=C(R4)-C00H VIIICH2 = C (R4) -C00H VIII
25 hvor R4 har den ovenfor anførte betydning.Wherein R4 is as defined above.
Additionen af en forbindelse med formlen VII til en forbindelse med formlen VIII foretages bekvemt under betingelser- 7The addition of a compound of formula VII to a compound of formula VIII is conveniently made under conditions- 7
DK 165113BDK 165113B
ne for en Michael-addition eller modifikationer deraf.ne for a Michael addition or modifications thereof.
Additionen foretages bekvemt under opvarmning. Forbindelsen med formlen VII kan anvendes i sin saltform (carboxylat-salt), fx alkalimetalsaltform, fx Na-carboxylatformen. For-5 bindeisen med formlen VII kan imidlertid også anvendes i sin frie syreform, i hvilket tilfælde additionen bekvemt udføres i nærværelse af en tertiær amin, fx en trialkylamin såsom tri(n-butyl)amin, eller et acetat af Fe, Co(II) eller Ni(II). Sidstnævnte procesvariant kan udføres i fravær af 10 opløsningsmiddel, reaktionen foregår hurtigt med højt udbytte, ikke-omsat udgangsmateriale kan genvindes, og forbindelserne med formlen VI kan cycliseres til dannelse af forbindelser med formlen IV, uden at det er nødvendigt at isolere forbindelserne med formlen VI.The addition is conveniently made during heating. The compound of formula VII may be used in its salt form (carboxylate salt), for example, the alkali metal salt form, for example the Na carboxylate form. However, the compound of formula VII may also be used in its free acid form, in which case the addition is conveniently carried out in the presence of a tertiary amine, for example a trialkylamine such as tri (n-butyl) amine, or an acetate of Fe, Co (II). ) or Ni (II). The latter process variant can be carried out in the absence of solvent, the reaction proceeds rapidly with high yield, unreacted starting material can be recovered, and the compounds of formula VI can be cyclized to form compounds of formula IV without the need to isolate the compounds of formula VI .
15 R2 er fortrinsvis CH3. R4 er fortrinsvis CH3. R betegner fortrinsvis CH(CH3)CH2OCH3, CH2CH2-0-nC3H7 eller CH2CH2-0-iC3H7, navnlig CH(CH3)-CH2-OCH3.Preferably R2 is CH3. Preferably, R 4 is CH 3. Preferably R represents CH (CH3) CH2OCH3, CH2CH2-O-nC3H7 or CH2CH2-O-C3H7, especially CH (CH3) -CH2-OCH3.
Opfindelsen belyses nærmere i nedenstående eksempler: EKSEMPEL 1 20 N-(1-Methoxyprop-2-y1)-2,4-dimethyltetrahydrothien-3-yli~ deniminThe invention is further elucidated in the Examples below: EXAMPLE 1 N- (1-Methoxyprop-2-yl) -2,4-dimethyltetrahydrothien-3-yl] denimine
En reaktionskolbe forsynes med termometer, vandkøler og en søjle, hvori der er 31 g molekylsi (5 Å).A reaction flask is provided with a thermometer, water cooler and a column containing 31 g of molecular sieve (5 Å).
I en reaktionskolbe hældes en blanding af 0,2 mol 2,4-di-25 methyltetrahydrothiophen-3-on, 0,225 mol l-methoxy-2-amino-propan og 50 ml cyclohexan. Reaktionskolben forsynes med termometer, vandkøler og en kolonne med 31 g molekylsi (5 Å) på en sådan måde, at kondensatet fra den kogende reaktionsblanding kontinuert ledes gennem molekylsien.In a reaction flask is poured a mixture of 0.2 moles of 2,4-dimethyl tetrahydrothiophen-3-one, 0.225 moles of 1-methoxy-2-amino-propane and 50 ml of cyclohexane. The reaction flask is provided with a thermometer, water cooler and a column of 31 g of molecular sieve (5 Å) in such a way that the condensate from the boiling reaction mixture is continuously passed through the molecular sieve.
30 Apparaturet beskyttes med N2 for at udelukke atmosfærisk oxygen.The apparatus is protected with N2 to exclude atmospheric oxygen.
DK 165113BDK 165113B
δδ
Reaktionsblandingen koges i 9 timer. Titelforbindelsen vakuumdestilleres derefter ved 0,5 mm Hg i kogepunktsområdet 65-80°C.The reaction mixture is boiled for 9 hours. The title compound is then vacuum distilled at 0.5 mm Hg in the boiling range of 65-80 ° C.
EKSEMPEL 2 5 N-(l-Methoxyprop-2-yl)-2,4-dimethyl-3-aminothiophen 0,1 mol thionylchlorid opløst i 20 ml toluen dryppes under omrøring og afkøling ved 10-20°C til en opløsning af 0,1 mol N- (l-methoxyprop-2-y 1 )-2,4-dimethyltetrahydrothien-3 -ylidenimin i 80 ml toluen.EXAMPLE 2 N- (1-Methoxyprop-2-yl) -2,4-dimethyl-3-aminothiophene 0.1 mole of thionyl chloride dissolved in 20 ml of toluene is dripped with stirring and cooling at 10-20 ° C to a solution of 0 , 1 mole of N- (1-methoxyprop-2-yl) -2,4-dimethyltetrahydrothien-3-ylidenimine in 80 ml of toluene.
10 Reaktionsblandingen omrøres i 1 time og indstilles derefter på alkalisk reaktion med en koncentreret natriumhydroxidopløsning. Den organiske fase fraskilles, den vandige fase vaskes med vand og tørres, og toluenet afdestilleres i vakuum. Remanensen destilleres ved 0,2 mm Hg, hvorved 15 titelforbindelsen fås, kogepunkt 70-72°C.The reaction mixture is stirred for 1 hour and then adjusted to alkaline reaction with a concentrated sodium hydroxide solution. The organic phase is separated, the aqueous phase is washed with water and dried, and the toluene is distilled off in vacuo. The residue is distilled at 0.2 mm Hg to give the title compound, boiling point 70-72 ° C.
EKSEMPEL 3 N- (2,4-Dimethylthien-3-yl) -N- (l-methoxyprop-2-yl) chloracet-amid a) Anvendelse af en forbindelse med formlen II i saltform.Example 3 N- (2,4-Dimethylthien-3-yl) -N- (1-methoxyprop-2-yl) chloroacetamide a) Use of a compound of formula II in salt form.
20 0,02 mol thionylchlorid i 5 ml toluen dryppes i løbet af 40 minutter til 0,02 mol N-(l-methoxyprop-2-yl)-2,4-dimethyltetrahydrothien-3-ylidenimin op-løst i 10 ml toluen ved 20°C. Reaktionsblandingen omrøres i 2 timer, hvorved der fås hydrochloridet af N-(l-methoxyprop-2-yl)-2,4-dimethyl-25 3-aminothiophen. Der tilsættes derefter 0,02 mol chlorace-tylchlorid opløst i 5 ml toluen. Blandingen opvarmes til kogning under tilbagesvaling i 1 time, hvorved der undviger HC1. Titelforbindelsen fås ved søjlechromatografi på sili-20 0.02 moles of thionyl chloride in 5 ml of toluene are dropped over 40 minutes to 0.02 moles of N- (1-methoxyprop-2-yl) -2,4-dimethyltetrahydrothien-3-ylidenimine dissolved in 10 ml of toluene at 20 ° C. The reaction mixture is stirred for 2 hours to give the hydrochloride of N- (1-methoxyprop-2-yl) -2,4-dimethyl-3-aminothiophene. Then 0.02 mole of chloroacetyl chloride dissolved in 5 ml of toluene is added. The mixture is heated to reflux for 1 hour, thereby avoiding HCl. The title compound is obtained by column chromatography on silica gel.
DK 165113 BDK 165113 B
9 cagel med cyclohexan/ethylacetat (8:2), kogepunkt 148-150°C/0,03 mm Hg.9 cagel with cyclohexane / ethyl acetate (8: 2), boiling point 148-150 ° C / 0.03 mm Hg.
b) Anvendelse af en forbindelse med formlen II i baseform.b) Use of a compound of formula II in base form.
Til en blanding af 315 g (1,58 mol) N-(l-methyl-2-methoxy-5 ethyl)-2,4-dimethyl-3-aminothiophen i 1500 ml CH2CI2 og 240 g (1,75 mol) K2CO3 i 250 ml vand dryppes ved stuetemperatur og under kraftig omrøring 200 g (1,77 mol) chlorace-tylchlorid. Efter 1/2 times reaktionstid ved stuetemperatur fraskilles den organiske fase, vaskes to gange med hver 10 gang 200 ml vand, tørres over natriumsulfat og koncentreres ved inddampning.To a mixture of 315 g (1.58 mol) of N- (1-methyl-2-methoxy-5-ethyl) -2,4-dimethyl-3-aminothiophene in 1500 ml of CH 2 Cl 2 and 240 g (1.75 mol) of K 2 CO 3 in 250 ml of water is dropped at room temperature and with vigorous stirring 200 g (1.77 mole) of chloroacetyl chloride. After 1/2 hour reaction time at room temperature, the organic phase is separated, washed twice with 200 ml of water every 10 times, dried over sodium sulfate and concentrated by evaporation.
Titel forbindelserne fås ved chromatografi på silicagel med hexan/diethylether (85:15). Rf-Værdi = 0,3 (silicagel; diethylether/hexan 2:1), kogepunkt 148-150°C/0,03 mm Hg.The title compounds are obtained by chromatography on silica gel with hexane / diethyl ether (85:15). Rf value = 0.3 (silica gel; diethyl ether / hexane 2: 1), bp 148-150 ° C / 0.03 mm Hg.
15 EKSEMPEL 4 2,4-Dimethyltetrahydrothiophen-3-on Cyclisering af 2,5-dimethyl-3-thiaadipinsyre a) Med Fe-pulver 100 dele 2,5-dimethyl-3-thiaadipinsyre opvarmes til 180-20 220°C med 7,5 dele jernpulver. Det således vundne destillat opløses i CH2Cl2, vaskes med mættet vandig NaHC03-opløsning og tørres over Na2SC>4. Titel forbindelsen destilleres ved 2 mm Hg ved en temperatur på 39-40°C.EXAMPLE 4 2,4-Dimethyltetrahydrothiophen-3-one Cyclization of 2,5-dimethyl-3-thiaadipic acid a) With Fe powder 100 parts of 2,5-dimethyl-3-thiaadipic acid are heated to 180-20 220 ° C with 7 , 5 parts iron powder. The distillate thus obtained is dissolved in CH 2 Cl 2, washed with saturated aqueous NaHCO 3 solution and dried over Na 2 SC 4. The title compound is distilled at 2 mm Hg at a temperature of 39-40 ° C.
b) Med Ba(OH)2 25 En blanding af 0,94 mol 2,5-dimethyl-3-thiaadipinsyre og 10 g Ba(OH)2 opvarmes i 24 timer i en destillationskolbe til 230-250°C under omrøring. Destillatet ekstraheres medb) With Ba (OH) 2 A mixture of 0.94 mol of 2,5-dimethyl-3-thiaadipic acid and 10 g of Ba (OH) 2 is heated for 24 hours in a distillation flask to 230-250 ° C with stirring. The distillate is extracted with
DK 165113 BDK 165113 B
10 diethylether, og etheropløsningen tørres over magnesiumsul-fat og destilleres under reduceret tryk, kogepunkt 39-40°C ved 2 mm Hg.10 diethyl ether and the ether solution is dried over magnesium sulfate and distilled under reduced pressure, boiling point 39-40 ° C at 2 mm Hg.
c) Med eddikesyreanhydrid 5 0,5 mol 2,5-dimethyl-3-thiaadipinsyre, 300 ml eddikesyre anhydrid og 4 g LiCl omrøres i 6 timer ved 120°C. Den rå blanding hældes ud på is, og der tilsættes 10 cm3 koncentreret svovlsyre. Blandingen omrøres derefter natten over, indstilles på alkalisk reaktion med koncentreret NaOH-op-10 løsning under afkøling med isstykker og ekstraheres flere gange med diethylether. Etherfasen vaskes med vand, tørres over MgS04 og koncentreres ved inddampning. Remanensen destilleres over en Vigreux-kolonne, hvorved titelforbindelsen fås, kogepunkt 81-88°C/20 mm Hg.c) With acetic anhydride 5 0.5 moles of 2,5-dimethyl-3-thiaadipic acid, 300 ml of acetic anhydride and 4 g of LiCl are stirred for 6 hours at 120 ° C. The crude mixture is poured onto ice and 10 cm 3 of concentrated sulfuric acid is added. The mixture is then stirred overnight, adjusted to alkaline reaction with concentrated NaOH solution under cooling with ice pieces, and extracted several times with diethyl ether. The ether phase is washed with water, dried over MgSO 4 and concentrated by evaporation. The residue is distilled over a Vigreux column to give the title compound, boiling point 81-88 ° C / 20 mm Hg.
15 EKSEMPEL 5 2,5-Dimethyl-3-thiaadipinsyreEXAMPLE 5 2,5-Dimethyl-3-thiaadipic acid
Til en opløsning af 320 g (8 mol) NaOH i 1300 ml vand sættes i løbet af 15 minutter 424 g (4 mol) thiomælkesyre.To a solution of 320 g (8 moles) of NaOH in 1300 ml of water is added 424 g (4 moles) of thiolactic acid over 15 minutes.
Efter exoterm reaktion (35°C) tilsættes 344 g (4 mol) 20 methacrylsyre, og reaktionsblandingen omrøres derefter ved 80°C i 18 timer.After exothermic reaction (35 ° C), 344 g (4 moles) of 20 methacrylic acid are added and the reaction mixture is then stirred at 80 ° C for 18 hours.
Blandingen afkøles til 50°C, hældes ud på en blanding af 3 kg is og 750 ml koncentreret HC1 og ekstraheres fire gange med hver gang 1000 ml CH2C12. CH2Cl2-Ekstrakterne 25 tørres med Na2S04, hvorefter den organiske fase koncentreres ved inddampning i roterende kolbe, hvorved titelforbindelsen med smeltepunkt 78-80°C fås i form af farveløse krystaller.The mixture is cooled to 50 ° C, poured onto a mixture of 3 kg of ice and 750 ml of concentrated HCl and extracted four times with 1000 ml of CH2 Cl2 each time. The CH 2 Cl 2 extracts are dried over Na 2 SO 4 and the organic phase is concentrated by evaporation in a rotary flask to give the title compound, mp 78-80 ° C, in the form of colorless crystals.
Claims (4)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DK344785A DK165113C (en) | 1983-12-20 | 1985-07-29 | N- (ALCOXYLKYL) -2,4-DIALKYLTETRAHYDROTHIA-3-YLIDENIMINE DERIVATIVES AND PROCEDURES FOR THE PREPARATION OF N- (2,4-DIALKYLTHIEN-3-YL) -N- (ALKOXY-ALKYLDE) -2,4-DIALKYLTETRAHYDROTHIEN-3-YLIDENIMINDERIVATERNE |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH676083 | 1983-12-20 | ||
| CH6760/83A CH657129A5 (en) | 1983-12-20 | 1983-12-20 | Process for preparing N-thienylchloroacetamides |
| DK344785 | 1985-07-29 | ||
| DK344785A DK165113C (en) | 1983-12-20 | 1985-07-29 | N- (ALCOXYLKYL) -2,4-DIALKYLTETRAHYDROTHIA-3-YLIDENIMINE DERIVATIVES AND PROCEDURES FOR THE PREPARATION OF N- (2,4-DIALKYLTHIEN-3-YL) -N- (ALKOXY-ALKYLDE) -2,4-DIALKYLTETRAHYDROTHIEN-3-YLIDENIMINDERIVATERNE |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| DK344785D0 DK344785D0 (en) | 1985-07-29 |
| DK344785A DK344785A (en) | 1987-01-30 |
| DK165113B true DK165113B (en) | 1992-10-12 |
| DK165113C DK165113C (en) | 1993-03-01 |
Family
ID=25700132
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK344785A DK165113C (en) | 1983-12-20 | 1985-07-29 | N- (ALCOXYLKYL) -2,4-DIALKYLTETRAHYDROTHIA-3-YLIDENIMINE DERIVATIVES AND PROCEDURES FOR THE PREPARATION OF N- (2,4-DIALKYLTHIEN-3-YL) -N- (ALKOXY-ALKYLDE) -2,4-DIALKYLTETRAHYDROTHIEN-3-YLIDENIMINDERIVATERNE |
Country Status (1)
| Country | Link |
|---|---|
| DK (1) | DK165113C (en) |
-
1985
- 1985-07-29 DK DK344785A patent/DK165113C/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| DK344785A (en) | 1987-01-30 |
| DK344785D0 (en) | 1985-07-29 |
| DK165113C (en) | 1993-03-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| SU628812A3 (en) | Organic compound producing method | |
| DK170888B1 (en) | Process for the preparation of hydrochloride of 1-phenyl-1-diethylaminocarbonyl-2-aminomethyl-cyclopropane (Z) | |
| SU508199A3 (en) | Method for producing morpholine derivatives | |
| KR20020033617A (en) | Salts of 2,2-dimethyl-1,3-dioxane intermediates and process for the preparation thereof | |
| US6197976B1 (en) | Preparation of ketorolac | |
| EP0210320B1 (en) | Process for the preparation of n-thienyl-chloroacetamides | |
| NO166712B (en) | PROCEDURE FOR THE PREPARATION OF PYRROLIDO DERIVATIVES. | |
| DK165113B (en) | N-(Alkoxyalkyl)-2,4-dialkyltetrahydrothien-3-ylideneimine derivatives, and process for preparing N-(2,4- dialkylthien-3-yl)-N-(alkoxyalkyl)chloroacetamide derivatives using the N-(alkoxyalkyl)-2,4- dialkyltetrahydrothien-3-ylideneimine derivatives | |
| SU516341A3 (en) | Method for preparing substituted benzophenones | |
| KR930008230B1 (en) | Process for preparation of fluoromethyl-substituted piperidine carbodithioates | |
| US4188341A (en) | Process for the production of (substituted) 2,6-dimethylanilines | |
| KR100330609B1 (en) | Process for producing 3-isoxazolecarboxylic acid | |
| US4806656A (en) | Preparation of N-thienyl-chloroacetamides and tetrahydro-thien-3-ylidenimines | |
| US4440947A (en) | Preparation of substituted alpha-halogeno-propionic acids and their derivatives | |
| EP0010856B1 (en) | Halogenated hydrocarbons and a method for their preparation | |
| CA1263866A (en) | Process for the preparation of n-thienyl- chloroacetamides | |
| US5142091A (en) | α, β-unsaturated ketones and ketoxime derivatives | |
| SU439986A1 (en) | The method of obtaining derivatives tiyepina | |
| SU614743A3 (en) | Method of obtaining enol basic esters or salts thereof | |
| DK158038B (en) | METHOD OF PREPARING DI-N-PROPYLACETONITRIL | |
| KR20040034728A (en) | Method for producing 4-haloalkylnicotinic acid esters | |
| US3932507A (en) | Process for the chlorination of aromatic isocyanide dichlorides | |
| US4501921A (en) | Synthesis of alkylidene intermediates | |
| EP0017264B1 (en) | Bicyclic lactams and a process for their preparation | |
| IE58835B1 (en) | Process for the preparation of n-thienyl-chloroacetamides |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A0 | Application filed | ||
| PUP | Patent expired |