Process for the preparation of bicyclic amidines
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3 claims: 1 independent, 2 dependent
- 1Verfahren zur Herstellung' bicyclischer Amidine der allgemeinen Formel worin A ausgewählt ist aus der Gruppe -CR 1 R 2 -CR 3 R 4 -CR 5 R 6 -, -CR 1 R 2 -CR 3 R 4 -CR 5 R 6 -CR 7 R 8 -, -CR 1 R 2 -CR 3 R 4 -CR 5 R 6 -CR 7 R 8 -CR 9 R 10 -, worin die Substituenten in A jeweils vom Stickstoffatom ausgehend numeriert sind und B ausgewählt ist aus der Gruppe -CR 11 R 12 -CR 13 R 14 -, -CR 11 R 12 -CR 15 R 16 -CR 13 R 14 -, -CR 11 R 12 -CR 15 R 16 -CR 17 R 18 -CR 13 R 14 - und R 1 , R 2 und R 11 bis R 14 jeweils unabhängig voneinander Wasserstoff, C 1 -C 4 -Alkyl, Phenyl, alkylsubstituiertes Phenyl oder mit Hydroxy, Amino, C 1 -C 4 -Alkylamino oder Mercapto substituiertes C 1 -C 4 -Alkyl und R 3 bis R 10 und R 15 bis R 18 jeweils unabhängig voneinander Wasserstoff, C 1 -C 4 -Alkyl, Phenyl, alkylsubstituiertes Phenyl, Hydroxy, Amino, C 1 -C 4 -Alkylamino, Mercapto oder mit Hydroxy, Amino, C 1 -C 4 -Alkylamino oder Mercapto substituiertes C 1 -C 4 -Alkyl bedeuten, dadurch gekennzeichnet, dass ein Lacton der allgemeinen Formel worin A die oben genannte Bedeutung hat, mit einem Amin der allgemeinen Formel H 2 N―B―NH 2 III worin B die oben genannte Bedeutung hat, in Gegenwart eines sauren Katalysators auf wenigstens 150°C erhitzt wird wobei das Amin (III) in einer Menge von 2 bis 20 mol auf I mol des Lactons (II) eingesetzt wird, und das so erhaltene Reaktionsgemisch ohne Isolierung eines Zwischenprodukts einer fraktionierten Destillation unterworfen wird.
- 2Verfahren nach Anspruch 1, dadurch gekennzeichnet, dass als Lacton (II) eine Verbindung aus der Gruppe γ-Butyrolacton, γ-Valerolacton, δ-Valerolacton, ε-Caprolacton, Pantolacton eingesetzt wird.
- 3Verfahren nach Anspruch 1 oder 2, dadurch gekennzeichnet, dass als Amin (III) eine Verbindung aus der Gruppe 1,2-Diaminoethan, 1,2-Diaminopropan, 1,3-Diaminopropan, 1,2,3-Triaminopropan, 1,1,1-Tris(aminomethyl)ethan, Tetrakis(aminomethyl)methan eingesetzt Wird.
Independent claims3
47 paragraphs, as filed
The present invention relates to a new process for the preparation of bicyclic amidines by reacting lactones with primary amines.
Bicyclic amidines are strong organic bases, which have found numerous applications because of their high basicity with low nucleophilicity and their good solubility in almost all solvents. Particularly well known are the compounds 1,5-diazabicyclo [4.30] non-5-ene (2,3,4,6,7,8-hexahydropyrrolo [1,2-a] pylimidine) and usually designated by the abbreviations DBN and DBU 1,1,8-diazabicyclo [5.4.0] undec-7-ene (2,3,4,6,7,8,9,1 O-octahydropyrimido [1,2-a] azepine).
An overview of uses of these compounds in chemical syntheses can be found e.g. B. in "Synthetica Merck", Volume II, E. Merck, Darmstadt, 1974, pp. 118-119, 124.
A known production process for bicyclic amidines starts from N- (ω-aminoalkyl) lactones, which cyclize to the amidines when heated with acidic catalysts with elimination of water (DE-C-15 45 855).
The N- (ω-aminoalkyl) lactones are obtained, for example, from the corresponding cyano compounds by hydrogenation, in particular the N- (γ-aminopropyl) pyrrolidone from the N- (β-cyanoethyl) pyrrolidone (see, for example, BW Reppe et al., Justus Liebigs Ann. Chem. 1955, 596, p. 211).
It is also possible to prepare N- (ω-aminoalkyl) lactones from the corresponding lactones and α, ω-diaminoalkanes (DE-C-730 182).
The known processes for the preparation of bicyclic amidines have the disadvantage that they comprise at least two synthesis stages with the intermediate products being worked up.
It is known that bicyclic amidines are well suited as catalysts for the production of polyurethanes (FR-A 1 542 058).
The object of the present invention was therefore to demonstrate an improved and simplified process for the preparation of bicyclic amidines. According to the invention the object is achieved by the manufacturing method according to claim 1.
It has been found that it is possible to use bicyclic amidines of the general formula<chemistry id="chem0001" num="0001"><img file="EP0662476B2_D0001.tif" /></chemistry> in a one-pot process without isolation or purification of intermediates from the corresponding lactones of the general formula<chemistry id="chem0002" num="0002"><img file="EP0662476B2_D0002.tif" /></chemistry> and amines of the general formula H<sub>2</sub>N ― B ― NH<sub>2</sub> III to manufacture.
Group A in the lactone (II) and the amidine (I) each represents a 3-, 4- or 5-membered carbon chain of the formula -CR<sup>1</sup>R<sup>2</sup>-CR<sup>3</sup>R<sup>4</sup>-CR<sup>5</sup>R<sup>6</sup>-, -CR<sup>1</sup>R<sup>2</sup>-CR<sup>3</sup>R<sup>4</sup>-CR<sup>5</sup>R<sup>6</sup>-CR<sup>7</sup>R<sup>8</sup>- or -CR<sup>1</sup>R<sup>2</sup>-CR<sup>3</sup>R<sup>4</sup>-CR<sup>5</sup>R<sup>6</sup>-CR<sup>7</sup>R<sup>8</sup>-CR<sup>9</sup>R<sup>10</sup>-, where R<sup>1</sup> and R<sup>2</sup> are each bound to the carbon atom adjacent to the heteroatom.
The group B in the amine (III) and the amidine (I) each represents a 2-, 3- or 4-membered carbon chain of the formula -CR<sup>11</sup>R<sup>12</sup>-CR<sup>13</sup>R<sup>14</sup>-, -CR<sup>11</sup>R<sup>12</sup>-CR<sup>15</sup>R<sup>16</sup>-CR<sup>13</sup>R<sup>14</sup>- or -CR<sup>11</sup>R<sup>12</sup>-CR<sup>15</sup>R<sup>16</sup>-CR<sup>17</sup>R<sup>18</sup>-CR<sup>13</sup>R<sup>14</sup>-.
The general formula I thus includes bicyclic amidines with 5-, 6- or 7-membered rings, it being possible for the two rings to have the same or different number of members. Accordingly, the general formula II comprises lactones with 5 to 7 ring members, ie γ-, δ- and ε-lactones.
The substituents R<sup>1</sup>, R<sup>2</sup> and R<sup>11</sup> to R<sup>14</sup> carbon chains A and B are each independently hydrogen, C<sub>1</sub>-C<sub>4</sub>-Alkyl or aryl or C<sub>1</sub>-C<sub>4</sub>-Alkylgruppen, which in turn with hydroxy, amino, C<sub>1</sub>-C<sub>4</sub>-Alkylamino or Mercapto are substituted. The substituents R<sup>3</sup> to R<sup>10</sup> and R<sup>15</sup> to R<sup>18</sup> besides those for R<sup>1</sup>, R<sup>2</sup> and R<sup>11</sup> to R<sup>14</sup> mentioned groups still hydroxy, amino, C<sub>1</sub>-C<sub>4</sub>-Alkylamino or mercapto groups.
Under C<sub>1</sub>-C<sub>4</sub>Alkyl here means all primary, secondary and tertiary unbranched or branched alkyl groups with up to 4 carbon atoms, that is methyl, ethyl, propyl, butyl, isopropyl, isobutyl, sec-butyl and tert-butyl. Aryl is to be understood in particular as phenyl or alkyl-substituted phenyl, such as, for example, o-, m- or p-tolyl or the various isomeric xylyl groups. Suitable lactones are, for example, γ-butyrolactone, γ- and δ-valerolactone, ε-caprolactone or substituted lactones such as pantolactone (2-hydroxy-3,3-dimethyl-γ-butyro-lactone). Functional groups as substituents, that is to say hydroxy, amino, alkylamino or mercapto, are preferably located on group B of the amine component (III). Amines (III) are therefore not only primary diamines, but also compounds with additional primary or secondary amino groups. Suitable amines are, for example, 1,2-diaminoethane, 1,2-diaminopropane, 1,3-diaminopropane, 1,2,3-triaminopropane, 1,1,1-tris (aminomethyl) ethane or tetrakis (aminomethyl) methane. If amines with non-equivalent primary amino groups, such as 1,2-diaminopropane or 1,2,3-triaminopropane, are used, product mixtures may arise.
When the lactone (II) is reacted with the amine (III), 2 to 20 mol of amine are used per 1 mol of lactone. The excess of amine can be recovered when the reaction mixture is worked up.
The reaction is conveniently carried out at a temperature of at least 150 ° C. The reaction temperature is preferably between 200 and 300 ° C. An inert solvent such as toluene or xylene can be added, but is not required. The reaction is preferably carried out without a solvent. In order to achieve the reaction temperature, it is generally necessary to keep the reaction mixture under elevated pressure because the boiling points of many starting materials are lower than the reaction temperature at atmospheric pressure. Ordinary autoclaves can be used for this. An acid catalyst is added to accelerate the reaction. Brønsted acids such as hydrochloric acid, sulfuric acid, phosphoric acid or ammonium chloride or acidic aluminum silicates or acidic metal oxides such as tin (IV) oxide or antimony (III) oxide are suitable for this.
According to the invention, the reaction mixture is distilled directly without isolating an intermediate. For practical reasons, it is typically transferred from the autoclave to a distillation apparatus. If an appropriately equipped apparatus is available, which is suitable for both positive pressure and vacuum, the reaction of the lactone with the amine and the distillation can of course be carried out in one and the same apparatus. In the distillation, the water formed during the ring closure and the excess amine pass first, then the amidine. Depending on the boiling point of the product, the distillation is carried out under a correspondingly reduced pressure.
The process according to the invention can be used not only to prepare the known bicyclic amidines mentioned in the introduction, such as, for example, DBN and DBU, but in particular also new compounds from this class of substances with properties which have hitherto been achieved.
It has been found that those bicyclic amidines (I) in which at least one of the substituents R<sup>1</sup> to R<sup>18</sup> is or carries a primary or secondary amino group, a hydroxyl group and / or a mercapto group, can be used as a catalyst for the production of polyurethanes and is bound so firmly in the polymer that migration cannot be determined either in use or in the usual extraction tests. These additional functional groups presumably react with the isocyanate groups of the isocyanate component of the polyurethane to form covalent bonds in the production of the polyurethane.
The preparation of the compounds is particularly preferred<ul id="ul0001" list-style="none" compact="compact"><li>3-amino-2,3,4,6,7,8-hexahydropyrrolo [1,2-a] pyrimidine<chemistry id="chem0003" num="0003"><img file="EP0662476B2_D0003.tif" /></chemistry></li><li>3- (aminomethyl) -2,5,6,7-tetrahydro-3<i>H</i>-pyrrolo [1,2-a] imidazole<chemistry id="chem0004" num="0004"><img file="EP0662476B2_D0004.tif" /></chemistry></li></ul> both individually and as a mixture and 3- (aminomethyl) -3-methyl-2,3,4,6,7,8-hexahydropyrrolo [1,2-a] pyrimidine<chemistry id="chem0005" num="0005"><img file="EP0662476B2_D0005.tif" /></chemistry>
The following examples illustrate the implementation of the method according to the invention.
example 1
Preparation of 2,5,6,7-tetrahydro-3
<u>H</u>
-pyrrolo [1,2-a] imidazole (1,4-diazabicyclo- [3.3.0] oct-4-ene)
A mixture of 129 g (1.5 mol) of γ-butyrolactone, 8 g (0.15 mol) of ammonium chloride and 360 g (6 mol) of 1,2-diaminoethane was heated to 250 ° C. in an autoclave. After 2.5 hours the mixture was cooled and the excess diaminoethane and the water formed were distilled off. The residue was distilled at 200 ° C / 200 mbar. The remaining water was removed by heating the distillate in vacuo. Yield: 125 g (76%) colorless oil, which gradually solidifies to a waxy mass.
Example 2
Production of 3-amino-2,3,4,6,7,8-hexahydropyrrolo [1,2-a] pyrimidine and 3- (aminomethyl) -2,5,6,7-tetrahydro-3
<u>H</u>
pyrrolo [1,2-a] imidazole
Analogously to Example 1, 21.52 g (0.25 mol) of γ-butyrolactone, 1.34 g (25 mmol) of ammonium chloride and 83.43 g (0.94 mol) of 1,2,3-triaminopropane were reacted. The residue remaining after the excess amine and water had been distilled off was distilled at 170-200 ° C./0.1 mbar (bath temperature). Yield: 22.2 g (64%) yellowish oil Kp: 95 - 97 ° C / 2 mbar
According to GC, the product consisted of approximately 90% of the isomer with pyrrolo [1,2-a] pyrimidine skeleton and approximately 10% of the isomer with pyrrolo [1,2-a] imidazole skeleton.<u>3-amino-2,3,4,6,7,8-hexahydropyrrolo [1,2-a] pyrimidine</u><tables id="tabl0001" num="0001"><table frame="all"><tgroup cols="2" colsep="1" rowsep="0"><colspec colnum="1" colname="col1" colwidth="78.75mm" /><colspec colnum="2" colname="col2" colwidth="78.75mm" /><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left"><sup>1</sup>H-NMR (CDCl<sub>3</sub>, 400 MHz) δ:</entry><entry namest="col2" nameend="col2" align="left">1.96 (quint, 2H, H-7);</entry></row><row><entry namest="col1" nameend="col1" morerows="6" rowsep="1" /><entry namest="col2" nameend="col2" align="left">2.45 (t, 2H, H-8);</entry></row><row><entry namest="col2" nameend="col2" align="left">2.7-2.8 (m, 1H, H-4<sub>a</sub>);</entry></row><row><entry namest="col2" nameend="col2" align="left">3.05 (t, 1H, H-2<sub>a</sub>);</entry></row><row><entry namest="col2" nameend="col2" align="left">3.1 - 3.2 (m, 1H, H-3);</entry></row><row><entry namest="col2" nameend="col2" align="left">3.3 (t, 2H, H-6);</entry></row><row><entry namest="col2" nameend="col2" align="left">3.35 (t, 1H, H-4<sub>b</sub>);</entry></row><row rowsep="1"><entry namest="col2" nameend="col2" align="left">3.45 - 3.5 (m, 1H, H-2<sub>b</sub>).</entry></row></tbody></tgroup></table></tables><tables id="tabl0002" num="0002"><table frame="all"><tgroup cols="2" colsep="1" rowsep="0"><colspec colnum="1" colname="col1" colwidth="78.75mm" /><colspec colnum="2" colname="col2" colwidth="78.75mm" /><tbody valign="top"><row><entry namest="col1" nameend="col1" morerows="6" rowsep="1" align="left"><sup>13</sup>C-NMR (100 MHz) δ:</entry><entry namest="col2" nameend="col2" align="left">160.5 (s, C-8a);</entry></row><row><entry namest="col2" nameend="col2" align="left">52.88 (t, C-2);</entry></row><row><entry namest="col2" nameend="col2" align="left">51.4 (t, C-6);</entry></row><row><entry namest="col2" nameend="col2" align="left">50.9 (t, C-4);</entry></row><row><entry namest="col2" nameend="col2" align="left">43.0 (t, C-3);</entry></row><row><entry namest="col2" nameend="col2" align="left">30.9 (t, C-8);</entry></row><row rowsep="1"><entry namest="col2" nameend="col2" align="left">20.0 (t, C-7).</entry></row></tbody></tgroup></table></tables><u>3- (aminomethyl) -2,5,6,7-tetrahydro-3</u><i><u>H</u></i><u>-pyrrolo [1,2-a] imidazole</u><tables id="tabl0003" num="0003"><table frame="all"><tgroup cols="2" colsep="1" rowsep="0"><colspec colnum="1" colname="col1" colwidth="78.75mm" /><colspec colnum="2" colname="col2" colwidth="78.75mm" /><tbody valign="top"><row><entry namest="col1" nameend="col1" morerows="7" rowsep="1" align="left"><sup>1</sup>H-NMR (CDCl<sub>3</sub>, 400 MHz) δ:</entry><entry namest="col2" nameend="col2" align="left">2.28 - 2.32 (m, 2H, H-6);</entry></row><row><entry namest="col2" nameend="col2" align="left">2.32 - 2.35 (m, 2H, H-7);</entry></row><row><entry namest="col2" nameend="col2" align="left">2.75 (m, 1H, C<u>H</u><sub>a</sub>NH<sub>2</sub>);</entry></row><row><entry namest="col2" nameend="col2" align="left">2.85 (m, 2H, H-5);</entry></row><row><entry namest="col2" nameend="col2" align="left">3.3 (m, 1H, C<u>H</u><sub>b</sub>NH<sub>2</sub>);</entry></row><row><entry namest="col2" nameend="col2" align="left">3.4 (m, 1H, H -3);</entry></row><row><entry namest="col2" nameend="col2" align="left">3.8 (dd, 1H, H-2<sub>a</sub>);</entry></row><row rowsep="1"><entry namest="col2" nameend="col2" align="left">4.15 (dd, 1H, H-2<sub>b</sub>).</entry></row></tbody></tgroup></table></tables><tables id="tabl0004" num="0004"><table frame="all"><tgroup cols="2" colsep="1" rowsep="0"><colspec colnum="1" colname="col1" colwidth="78.75mm" /><colspec colnum="2" colname="col2" colwidth="78.75mm" /><tbody valign="top"><row><entry namest="col1" nameend="col1" morerows="6" rowsep="1" align="left"><sup>13</sup>C-NMR (CDCl<sub>3</sub>, 100 MHz) δ:</entry><entry namest="col2" nameend="col2" align="left">175.8 (s, C-7a);</entry></row><row><entry namest="col2" nameend="col2" align="left">64.5 (t, C-2);</entry></row><row><entry namest="col2" nameend="col2" align="left">64.3 (d, C-3);</entry></row><row><entry namest="col2" nameend="col2" align="left">45.8 (t, <u>C.</u>H<sub>2</sub>NH<sub>2</sub>);</entry></row><row><entry namest="col2" nameend="col2" align="left">44.3 (t, C-5);</entry></row><row><entry namest="col2" nameend="col2" align="left">25.4 (t, C-7);</entry></row><row rowsep="1"><entry namest="col2" nameend="col2" align="left">22.6 (t, C-6).</entry></row></tbody></tgroup></table></tables>
Example 3
Preparation of 3- (aminomethyl) -3-methyl-2,3,4,6,7,8-hexahydropyrrolo [1,2-a] pyrimidine
A mixture of 21.03 g (0.24 mol) of γ-butyrolactone and 1.31 g (24 mmol) of ammonium chloride in 114.5 g (0.98 mol) of 1,1,1-tris (aminomethyl) ethane was used in heated to 250 ° C in an autoclave. After 1.5 h, the mixture was cooled and the excess amine and the water formed were distilled off. The residue was distilled at 200-240 ° C / 18 mbar. Yield: 22.0 g (54%) yellowish oil Kp: 117-120 ° C / 1 mbar <tables id="tabl0005" num="0005"><table frame="all"><tgroup cols="2" colsep="1" rowsep="0"><colspec colnum="1" colname="col1" colwidth="78.75mm" /><colspec colnum="2" colname="col2" colwidth="78.75mm" /><tbody valign="top"><row><entry namest="col1" nameend="col1" morerows="7" rowsep="1" align="left"><sup>1</sup>H-NMR (CDCl<sub>3</sub>, 400 MHz) δ:</entry><entry namest="col2" nameend="col2" align="left">0.91 (s, 3H, CH<sub>3</sub>);</entry></row><row><entry namest="col2" nameend="col2" align="left">1.95 (quint, 2H, H-7);</entry></row><row><entry namest="col2" nameend="col2" align="left">2.45 (t, 2H, H-8);</entry></row><row><entry namest="col2" nameend="col2" align="left">2.53 (dd, 2H, C<u>H</u><sub>2</sub>NH<sub>2</sub>);</entry></row><row><entry namest="col2" nameend="col2" align="left">2.84 (dd, 1H, H-4<sub>a</sub>);</entry></row><row><entry namest="col2" nameend="col2" align="left">3.0 (m, 2H, H-2<sub>a</sub>, H-4<sub>b</sub>);</entry></row><row><entry namest="col2" nameend="col2" align="left">3.13 (dd, 1H, H-2<sub>b</sub>);</entry></row><row rowsep="1"><entry namest="col2" nameend="col2" align="left">3.28 (dt, 2H, H-6).</entry></row></tbody></tgroup></table></tables><tables id="tabl0006" num="0006"><table frame="all"><tgroup cols="2" colsep="1" rowsep="0"><colspec colnum="1" colname="col1" colwidth="78.75mm" /><colspec colnum="2" colname="col2" colwidth="78.75mm" /><tbody valign="top"><row><entry namest="col1" nameend="col1" morerows="2" align="left"><sup>13</sup>C-NMR (CDCl<sub>3</sub>, 100 MHz) δ:</entry><entry namest="col2" nameend="col2" align="left">160.1 (s, C-8a);</entry></row><row><entry namest="col2" nameend="col2" align="left">53.5 (t, C-2);</entry></row><row><entry namest="col2" nameend="col2" align="left">51.5 (t, C-6);</entry></row><row><entry namest="col1" nameend="col1" morerows="5" rowsep="1" /><entry namest="col2" nameend="col2" align="left">51.3 (t, C-4)</entry></row><row><entry namest="col2" nameend="col2" align="left">48.5 (t, <u>C.</u>H<sub>2</sub>NH<sub>2</sub>);</entry></row><row><entry namest="col2" nameend="col2" align="left">32.0 (s, C-3);</entry></row><row><entry namest="col2" nameend="col2" align="left">30.9 (t, C-8);</entry></row><row><entry namest="col2" nameend="col2" align="left">20.9 (q, <u>C.</u>H<sub>3</sub>);</entry></row><row rowsep="1"><entry namest="col2" nameend="col2" align="left">19.9 (t, C-7).</entry></row></tbody></tgroup></table></tables>
Example 4
Preparation of 2,5,6,7-tetrahydro-3
<u>H</u>
-pyrrolo [1,2-a] imidazole
A mixture of 86 g (1 mol) of γ-butyrolactone and 2 ml of 98% sulfuric acid in 240 g (4 mol) of 1,2-diaminoethane was heated to 250 ° C. in an autoclave. After 4.5 h, the reaction mixture was cooled and worked up as described in Example 1. Yield: 90 g (82%), properties see example 1.
Example 5
Preparation of 2,3,4,6,7,8-hexahydropyrrolo [1,2-a] pyrimidine (1,5-diazabicyclo- [4.3.0] non-5-ene, DBN)
A mixture of 43 g (0.5 mol) of γ-butyrolactone and 2.68 g (25 mmol) of ammonium chloride in 148 g (2 mol) of 1,3-diaminopropane was heated to 250 ° C. in an autoclave. After 4.5 hours, the mixture was cooled and the excess amine and the water formed were distilled off to 250 mbar. The residue was distilled in vacuo. Yield: 47 g (75%) colorless liquid Kp: 98 ° C / 12 mbar
Example 6
Preparation of 2,3,4,6,7,8,9,10-octahydropyrimido [1,2-a] azepine (1,8-diazabicyclo- [5.4.0] undec-7-ene, DBU)
The procedure was as described in Example 5, with the difference that 57 g (0.5 mol) of ε-caprolactone were used instead of γ-butyrolactone. Yield: 16 g (21%) colorless liquid Kp: 115 ° C / 8 mbar
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Every citation, both waysCites: the store holds 3 of 4
| Document | Relation | Office | Cited during |
|---|---|---|---|
| EP0199483A | Cites | European Patent Office (EPO) | – |
| DE1545855A | Cites | Germany | – |
| GB1182014A | Cites | United Kingdom | – |
| PHARMAZIE, Bd.47, Nr.6, 1992 Seiten 403 - 409 MOEHRLE,H;OTTERSBACH,D; STEIGEL,A 'Ring-chain isomerism of fused alpha-amino nitrones' | Non-patent | – | – |
| J.W. Copenhaver et al. "Acetylene and Carbon Monoxide Chemistry", Reinhold Publishing Corp., New York, 1949, Seiten 164-165 | Non-patent | – | – |
| J.W. Copenhaver et al. "Acetylene and Carbon Monoxide Chemistry", Reinhold Publishing Corp., New York, 1949, Seiten 164-165 | Non-patent | – | Opposition |
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| US6255488B1 | United States of America | B1 | |
| CN1070861C | China | C | |
| EP0869127B1 | European Patent Office (EPO) | B1 | |
| AT206711T | Austria | T | |
| ATE206711T1 | Austria | T1 | |
| DE59409907D1 | Germany | D1 | |
| DK0869127T3 | Denmark | T3 | |
| SI0869127T1 | Slovenia | T1 | |
| ES2165114T3 | Spain | T3 | |
| US2002028939A1 | United States of America | A1 | |
| PT869127E | Portugal | E | |
| EP0662476B2This record | European Patent Office (EPO) | B2 | |
| DK0662476T4 | Denmark | T4 | |
| US6476175B2 | United States of America | B2 | |
| ES2128490T5 | Spain | T5 | |
| KR100362543B1 | Republic of Korea | B1 | |
| CA2134009C | Canada | C | |
| JP4348747B2 | Japan | B2 |
87 legal events, as 10 offices reported them to INPADOC
Over the term
Point at a mark for the eventEvents
| Event | Code | Office | |
|---|---|---|---|
| Lapsed in a contracting state [announced via postgrant information from national office to epo]LapsedPG25 | PG25 | EP | |
| Lapsed in a contracting state [announced via postgrant information from national office to epo]LapsedPG25 | PG25 | EP | |
| Lapsed in a contracting state [announced via postgrant information from national office to epo]LapsedPG25 | PG25 | EP | |
| Lapsed in a contracting state [announced via postgrant information from national office to epo]LapsedPG25 | PG25 | EP | |
| Lapsed in a contracting state [announced via postgrant information from national office to epo]LapsedPG25 | PG25 | EP | |
| Announcement of lapse in spainLapsedFD2A | FD2A | ES | |
| Lapsed in a contracting state [announced via postgrant information from national office to epo]LapsedPG25 | PG25 | EP | |
| Lapsed in a contracting state [announced via postgrant information from national office to epo]LapsedPG25 | PG25 | EP | |
| Lapsed in a contracting state [announced via postgrant information from national office to epo]LapsedPG25 | PG25 | EP | |
| Lapsed in a contracting state [announced via postgrant information from national office to epo]LapsedPG25 | PG25 | EP | |
| Lapsed in a contracting state [announced via postgrant information from national office to epo]LapsedPG25 | PG25 | EP | |
| Lapsed in a contracting state [announced via postgrant information from national office to epo]LapsedPG25 | PG25 | EP | |
| Lapsed in a contracting state [announced via postgrant information from national office to epo]LapsedPG25 | PG25 | EP | |
| Lapsed in a contracting state [announced via postgrant information from national office to epo]LapsedPG25 | PG25 | EP | |
| Lapsed in a contracting state [announced via postgrant information from national office to epo]LapsedPG25 | PG25 | EP | |
| Notification of lapseLapsedST | ST | FR | |
| Patent lapsedLapsedMM4A | MM4A | IE | |
| Lapsed in a contracting state [announced via postgrant information from national office to epo]LapsedPG25 | PG25 | EP | |
| Gb: european patent ceased through non-payment of renewal feeCeasedGBPC | GBPC | EP | |
| Ep patent lapsedLapsedEBP | EBP | DK | |
| Patent ceasedCeasedPL | PL | CH | |
| Se: european patent has lapsedLapsedEUG | EUG | EP | |
| Lapsed because of non-payment of the annual feeLapsedV1 | V1 | NL | |
| Be: lapsedLapsedBERE | BERE | EP | |
| Annulment/lapse due to non-payment of fees, searched and examined patentLapsedLAPSE DUE TO NON-PAYMENT OF FEESMM4A | MM4A | PT | |
| Annual fee paid to national office [announced via postgrant information from national office to epo]GrantedPGFP | PGFP | EP | |
| Annual fee paid to national office [announced via postgrant information from national office to epo]GrantedPGFP | PGFP | EP | |
| Annual fee paid to national office [announced via postgrant information from national office to epo]GrantedPGFP | PGFP | EP | |
| Annual fee paid to national office [announced via postgrant information from national office to epo]GrantedPGFP | PGFP | EP | |
| Annual fee paid to national office [announced via postgrant information from national office to epo]GrantedPGFP | PGFP | EP | |
| Annual fee paid to national office [announced via postgrant information from national office to epo]GrantedPGFP | PGFP | EP | |
| Annual fee paid to national office [announced via postgrant information from national office to epo]GrantedPGFP | PGFP | EP | |
| Annual fee paid to national office [announced via postgrant information from national office to epo]GrantedPGFP | PGFP | EP | |
| Annual fee paid to national office [announced via postgrant information from national office to epo]GrantedPGFP | PGFP | EP | |
| Annual fee paid to national office [announced via postgrant information from national office to epo]GrantedPGFP | PGFP | EP | |
| Annual fee paid to national office [announced via postgrant information from national office to epo]GrantedPGFP | PGFP | EP | |
| Annual fee paid to national office [announced via postgrant information from national office to epo]GrantedPGFP | PGFP | EP | |
| Annual fee paid to national office [announced via postgrant information from national office to epo]GrantedPGFP | PGFP | EP | |
| Valid on the event dateIF | IF | SI | |
| Fr: translation filed ** decision concerning oppositionOppositionET3 | ET3 | EP | |
| Lapsed in a contracting state [announced via postgrant information from national office to epo]LapsedPG25 | PG25 | EP | |
| Patent modifiedDC2A | DC2A | ES | |
| Nl: receipt of modified translations in the netherlands language after an opposition procedureOppositionNLR3 | NLR3 | EP | |
| Amended ep patent with danish claimsT4 | T4 | DK | |
| Nl: decision of oppositionOppositionNLR2 | NLR2 | EP | |
| Scope or validity of the patent modifiedAUFRECHTERHALTUNG DES PATENTES IN GEAENDERTER FORMAEN | AEN | CH | |
| Gb: translation of amended ep patent filed (gb section 77(6)(b)/1977)GBTA | GBTA | EP | |
| Patent maintained in amended form27A | 27A | EP | |
| Designated contracting statesAK | AK | EP | |
| Request for extension of the european patentSI PAYMENT 19941110AX | AX | EP | |
| Patent maintained in amended formORIGINAL CODE: 0009272PUAH | PUAH | EP | |
| Information on the status of an ep patent application or granted ep patentGrantedSTATUS: PATENT MAINTAINED AS AMENDEDSTAA | STAA | EP | |
| Interlocutory decision in oppositionOppositionORIGINAL CODE: EPIDOS IDOPPLAW | PLAW | EP | |
| European patent in force as of 2002-01-01IF02 | IF02 | GB | |
| Title (correction)PROCESS FOR THE PREPARATION OF BICYCLIC AMIDINESRTI2 | RTI2 | EP | |
| Title (correction)PROCESS FOR THE PREPARATION OF BICYCLIC AMIDINESRTI2 | RTI2 | EP | |
| Name/firm changedLONZA AG,(GESCHAEFTSLEITUNG: 4002 BASEL),CH-3945 GAMPEL/WALLIS (CH) TRANSFER- LONZA AG,LONZASTRASSE,3930 VISP (CH)PFA | PFA | CH | |
| Interlocutory decision in oppositionOppositionORIGINAL CODE: EPIDOS IDOPPLAW | PLAW | EP | |
| Reply of patent proprietor to notice(s) of oppositionOppositionORIGINAL CODE: EPIDOS OBSOPLBF | PLBF | EP | |
| Reply of patent proprietor to notice(s) of oppositionOppositionORIGINAL CODE: EPIDOS OBSOPLBF | PLBF | EP | |
| Reply of patent proprietor to notice(s) of oppositionOppositionORIGINAL CODE: EPIDOS OBSOPLBF | PLBF | EP | |
| Nl: opposition has been filed with the epoOppositionNLR1 | NLR1 | EP | |
| Opposition filedOpposition26 | 26 | EP | |
| Reply of patent proprietor to notice(s) of oppositionOppositionORIGINAL CODE: EPIDOS OBSOPLBF | PLBF | EP | |
| Opposition filedOppositionORIGINAL CODE: 0009260PLBI | PLBI | EP | |
| Ep patent with danish claimsT3 | T3 | DK | |
| Definitive protectionFG2A | FG2A | ES | |
| Fr: translation filedET | ET | EP | |
| It: translation for a ep patent filedITF | ITF | EP | |
| It: translation for a ep patent filedITF | ITF | EP | |
| Corresponds to:REF | REF | EP | |
| European patents granted designating irelandGrantedGERMANFG4D | FG4D | IE | |
| Gb: translation of ep patent filed (gb section 77(6)(a)/1977)GBT | GBT | EP | |
| European patent takes effect as a national patent in ch/liEP | EP | CH | |
| Designated contracting statesAK | AK | EP | |
| Request for extension of the european patentSI PAYMENT 941110AX | AX | EP | |
| Corresponds to:REF | REF | EP | |
| (expected) grantORIGINAL CODE: 0009210GRAA | GRAA | EP | |
| Despatch of communication of intention to grant a patentORIGINAL CODE: EPIDOS IGRAGRAH | GRAH | EP | |
| Despatch of communication of intention to grantORIGINAL CODE: EPIDOS AGRAGRAG | GRAG | EP | |
| Despatch of communication of intention to grant a patentORIGINAL CODE: EPIDOS IGRAGRAH | GRAH | EP | |
| Despatch of communication of intention to grantORIGINAL CODE: EPIDOS AGRAGRAG | GRAG | EP | |
| First examination report despatched17Q | 17Q | EP | |
| Request for examination filed17P | 17P | EP | |
| Designated contracting statesAK | AK | EP | |
| Requested extension states of the european patent have changedSI PAYMENT 941110RAX | RAX | EP | |
| Public reference made under article 153(3) epc to a published international application that has entered the european phaseORIGINAL CODE: 0009012PUAI | PUAI | EP |
Numbers
- Publication
- 0662476
- Publication, DOCDB
- 0662476
- Publication, EPODOC
- EP0662476
- Application
- 94117768
- Application, DOCDB
- 94117768
- Application, EPODOC
- EP19940117768
Titles3
- German
- Verfahren zur Herstellung Bicyclischer Amidine
- English
- Process for the preparation of bicyclic amidines
- French
- Procédé pour la préparation d' amidines bicycliques
Classification
- CPC, 1
- C07D487/04
- IPC, 2
- C07D471 04
- C07D487 04
Designated states2
- Contracting states, 1
- Sweden
- Extension states, 1
- Slovenia