NO161558B - ANALOGY PROCEDURE FOR THE PREPARATION OF ANTIHYPERTENSIVE BENZAZEPIN-2-ONER. - Google Patents
ANALOGY PROCEDURE FOR THE PREPARATION OF ANTIHYPERTENSIVE BENZAZEPIN-2-ONER. Download PDFInfo
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- NO161558B NO161558B NO822722A NO822722A NO161558B NO 161558 B NO161558 B NO 161558B NO 822722 A NO822722 A NO 822722A NO 822722 A NO822722 A NO 822722A NO 161558 B NO161558 B NO 161558B
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- vinyl chloride
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- 238000000034 method Methods 0.000 title claims description 10
- 230000003276 anti-hypertensive effect Effects 0.000 title 1
- 239000000178 monomer Substances 0.000 claims description 32
- 238000006116 polymerization reaction Methods 0.000 claims description 30
- 229920000642 polymer Polymers 0.000 claims description 18
- BZHJMEDXRYGGRV-UHFFFAOYSA-N Vinyl chloride Chemical compound ClC=C BZHJMEDXRYGGRV-UHFFFAOYSA-N 0.000 claims description 16
- 238000006243 chemical reaction Methods 0.000 claims description 9
- 229920001577 copolymer Polymers 0.000 claims description 9
- 238000003756 stirring Methods 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 238000012662 bulk polymerization Methods 0.000 claims description 3
- 239000012429 reaction media Substances 0.000 claims 1
- 239000003054 catalyst Substances 0.000 description 15
- 230000001105 regulatory effect Effects 0.000 description 9
- 239000002245 particle Substances 0.000 description 8
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 7
- 230000005484 gravity Effects 0.000 description 7
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 229910052760 oxygen Inorganic materials 0.000 description 5
- 239000001301 oxygen Substances 0.000 description 5
- 238000007334 copolymerization reaction Methods 0.000 description 3
- 238000007872 degassing Methods 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 229910001220 stainless steel Inorganic materials 0.000 description 2
- 239000010935 stainless steel Substances 0.000 description 2
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000007664 blowing Methods 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000010943 off-gassing Methods 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 229920002959 polymer blend Polymers 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D223/16—Benzazepines; Hydrogenated benzazepines
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
- C07K5/022—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -X-C(=O)-(C)n-N-C-C(=O)-Y-; X and Y being heteroatoms; n being 1 or 2
- C07K5/0222—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -X-C(=O)-(C)n-N-C-C(=O)-Y-; X and Y being heteroatoms; n being 1 or 2 with the first amino acid being heterocyclic, e.g. Pro, Trp
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
- C07K5/06026—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atom, i.e. Gly or Ala
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06086—Dipeptides with the first amino acid being basic
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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- Proteomics, Peptides & Aminoacids (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
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Description
Fremgangsmåte til fremstilling av polymere og kopolymere på Process for the production of polymers and copolymers on
basis av vinylklorid ved massepolymerisasjon i to trinn. basis of vinyl chloride by mass polymerization in two stages.
Foreliggende oppfinnelse vedrorer fremstilling av poly- The present invention relates to the production of poly-
mere eller kopolymere på basis av vinylklorid, ved homopolymerisa- more or copolymers based on vinyl chloride, by homopolymerisation
sjon eller kopolymerisasjon i to trinn. tion or copolymerization in two steps.
Det er allerede foreslått å utfore homo- eller kopoly-merisasjonen ut fra vesentlig vinylklorid idet man anvender en rbrehastighet som er så hby som mulig, inntil man i et forste trinn oppnår en omsetningsgrad for den eller de monomere på om- It has already been proposed to carry out the homo- or copolymerization from essentially vinyl chloride, using a reaction rate that is as high as possible, until in a first step a conversion rate for the monomer(s) of
kring 7 til 12 fof fortrinnsvis omkring 10 hvoretter rorehastig- around 7 to 12 fof, preferably around 10, after which the rudder speed
heten i annet trinn nedsettes til en så svak roring som mulig, som imidlertid må være tilstrekkelig til å sikre en god temperaturut-jevning i reaksjonsblandingen, hvorunder nevnte polymeriserings- the heat in the second step is reduced to as little stirring as possible, which, however, must be sufficient to ensure a good temperature equalization in the reaction mixture, during which said polymerization
prosesser utfores i en enkel apparatur og i nærvær av en katalysator. processes are carried out in a simple apparatus and in the presence of a catalyst.
Denne fremgangsmåte til fremstilling av polymere eller kopolymere gir produkter med utmerkede tetthetsegenskaper og storrelsesfordeling, men man må ifolge denne metode underkaste hele monomermassen det forste polymerisasjonstrinn. This method for producing polymers or copolymers gives products with excellent density properties and size distribution, but according to this method the entire monomer mass must be subjected to the first polymerization step.
Det er funnet at det er mulig å fremstille polymere eller kopolymere på basis av vinylklorid med lignende egenskaper som nevnt ovenfor, men hvor produktet har en jevnere eller i snevrere storrelsesfordeling, som dessuten kan varieres praktisk talt etter onske. It has been found that it is possible to produce polymers or copolymers based on vinyl chloride with similar properties as mentioned above, but where the product has a more uniform or narrower size distribution, which can also be varied practically as desired.
Foreliggende oppfinnelse består således i en fremgangsmåte til fremstilling av polymere eller kopolymere på basis av vinylklorid ved massepolymerisasjon i to trinn, hvilken finner sted i samme polymerisasjonsapparat, idet det forste trinn gjennomfores under så sterk omroring som mulig, inntil det er oppnådd en om-dannelsesgrad på 7 - 15 vektprosent og fortrinnsvis 8 \- 10 vektprosent av den innforte monomer, og det annet trinn gjennomfores under en omroring som er langsom, men tilstrekkelig til å sikre kontroll av reaksjonsmiljoets temperatur inntil endt polymerisasjon, og den karakteriseres ved at det forste polymerisasjonstrinn gjennomfores på l/3 til l/2 av den totale monomermengde som skal underkastes polymerisasjon, hvoretter det herved erholdte produkt suppleres med den resterende monomermengde og underkastes det annet polymerisasjonstrinn. The present invention thus consists in a method for producing polymers or copolymers based on vinyl chloride by mass polymerization in two stages, which takes place in the same polymerization apparatus, the first stage being carried out under as strong stirring as possible, until a degree of conversion is achieved of 7 - 15 percent by weight and preferably 8 \- 10 percent by weight of the introduced monomer, and the second step is carried out under a stirring which is slow, but sufficient to ensure control of the temperature of the reaction environment until the end of polymerization, and it is characterized by the fact that the first polymerization step is carried out on l/3 to l/2 of the total amount of monomer to be subjected to polymerization, after which the product thus obtained is supplemented with the remaining amount of monomer and subjected to the second polymerization step.
Ovenfor nevnte mengde monomer tilsatt i forste polymeri-sas jonstrinn representerer en omtrentlig nedre grense,' men denne utgangsandel kan ligge noe hbyere eller noe lavere avhengig av reak-sjonsbetingelsene, og særlig av rorehastigheten under'forste trinn. For en gitt monomermengde under forste polymerisasjonstrinn vil The above-mentioned amount of monomer added in the first polymerization step represents an approximate lower limit, but this starting proportion can be somewhat higher or somewhat lower depending on the reaction conditions, and in particular on the stirring speed during the first step. For a given amount of monomer during the first polymerization step will
en hoyere rorehastighet gi opphav til dannelse av flere vekstsentra (voksende polymerkjeder). a higher stirring speed gives rise to the formation of more growth centers (growing polymer chains).
Det er funnet at under forutsetning av at dé angitte reaksjonsbetingelser folges, vil det ikke danne seg noen ytter-ligere vekstsentra i lopet av annet polymerisasjonstrinn, og at dette annet polymerisasjonstrinn således i overveiendé grad be-virker en vekst og storrelsesokning på de polymerpartikler som allerede er dannet i forste polymerisasjonstrinn. It has been found that, provided that the stated reaction conditions are followed, no further growth centers will form during the second polymerization step, and that this second polymerization step thus predominantly causes a growth and increase in size of the polymer particles that have already is formed in the first polymerization step.
For å oppnå gode resultater bor mengden monomer som satses i forste trinn ligge mellom omkring 1/3 og 1/2: av den totalt To achieve good results, the amount of monomer used in the first step should be between about 1/3 and 1/2: of the total
satsede mengde. bet amount.
Por utforelse av oppfinnelsens fremgangsmåte anvendes med fordel de samme generelle betingelser og apparatur som beskrevet i fransk patent nr. 1.357.736 med tilleggspatenter, og det skal også gis eksempler på slik apparatur i det folgende. For carrying out the method of the invention, the same general conditions and apparatus as described in French patent no. 1,357,736 with additional patents are advantageously used, and examples of such apparatus shall also be given in the following.
Man kan likeledes utfore fremgangsmåten i nærvær av et katalysatorpar, nemlig en forste hurtig dekomponerende katalysator og en annen langsomt dekomponerende katalysator. The method can also be carried out in the presence of a pair of catalysts, namely a first rapidly decomposing catalyst and a second slowly decomposing catalyst.
Foruten muligheten for oppnåelse av polymere og kopolymere med snever storrelsesfordeling og regulerbar granulatdiameter, frembyr foreliggende oppfinnelse også disse fordeler: Idet man bare i forste trinn polymeriserer en del av den totale monomermengde, kan roreverket med tilhorende motor dimen-sjoneres mindre. In addition to the possibility of obtaining polymers and copolymers with a narrow size distribution and adjustable granule diameter, the present invention also offers these advantages: As one only polymerizes a part of the total monomer quantity in the first step, the agitator with associated motor can be dimensioned smaller.
Idet monomer-sammensetningens volum i forste trinn er mindre, er det mulig å oppnå meget hbye rorehastigheter, spesielt ved hjelp av turbinrorere, med lite kraftforbruk, men under oppnåelse åv hbye rorehastigheter. As the volume of the monomer composition in the first stage is smaller, it is possible to achieve very high stirring speeds, especially with the help of turbine stirrers, with little power consumption, but while achieving high stirring speeds.
Nedenfor gis i illustrerende og ikke begrensende hensikt noen eksempler på foretrukne utfbrelser i henhold til fremgangsmåten. Below are given, for illustrative and non-limiting purposes, some examples of preferred embodiments according to the method.
Eksempel 1 Example 1
Dette eksempel gis for sammenligningens skyld og beskriver en to-trinns polymerisasjon utfort i en enkelt apparatur, men hvor de to trinn utfores med den totale monomermasse i nærvær av en enkelt katalysator. This example is given for the sake of comparison and describes a two-stage polymerization carried out in a single apparatus, but where the two stages are carried out with the total monomer mass in the presence of a single catalyst.
I en autoklav utfort i rustfritt stål og med kapasitet 500 1, dessuten utstyrt med dobbelt ramme-rbreverk, ifylles 200 kg vinylklorid og 32 g eller 0,016 vektprosent azodiisobutyronitril som katalysator, etter at autoklaven forst er befridd for oksygen. Rammeverks-rbrerens hastighet reguleres til 100 omdreininger pr. minutt i lbpet av dette forste polymerisasjonstrinn. 200 kg of vinyl chloride and 32 g or 0.016% by weight of azodiisobutyronitrile as a catalyst are filled into an autoclave made of stainless steel and with a capacity of 500 1, also equipped with a double frame, after the autoclave has first been freed of oxygen. The speed of the framework rotor is regulated to 100 revolutions per minute in the lbpet of this first polymerization step.
Reaksjonsblandingens temperatur heves raskt til 62°C og holdes på denne temperatur, hvilket fit relativt trykk på 9,3 ato i autoklaven. Etter 3 t~ trinn nedsettes rbrerens hastighet The temperature of the reaction mixture is quickly raised to 62°C and maintained at this temperature, which corresponds to a relative pressure of 9.3 ato in the autoclave. After 3 t~ steps, the speed of the rbrere is reduced
og denne hastighet holdes under an. and this speed is kept under control.
i 13 timer. Den ikke polymerisert for 13 hours. It not polymerized
nede polymer. Man får i 68 $ utbyl down polymer. For $68 you get extras
tilsynelatende egenvekt 0,56. apparent specific gravity 0.56.
Storrelsesfordelingen på det fremstilte produkt fremgår av nedenstående tabell. The size distribution of the manufactured product is shown in the table below.
iin
Eksempel II Example II
Dette eksempel utfores i henhold til foreliggende opp-finnelses fremgangsmåte. Mengdeforholdet mellom monomermengden i forste polymerisasjonstrinn og den totale monomermengde er lik 1/2. This example is carried out according to the method of the present invention. The quantity ratio between the quantity of monomer in the first polymerization step and the total quantity of monomer is equal to 1/2.
I en autoklav på 500 1 av samme type som beskrevet i eksempel 1, innfores etter forutgående utblåsning av oksygen ved hjelp av 10 kg vinylkloridmonomer, 100 kg monomer samt 16 g azodiisobutyronitril-katalysator, dvs. en prosent på 0,016 i forhold til satset mono.ner.. Rammeverksrorerens hastighet reguleres til 100 omdreininger pr. minutt. Blandingens temperatur bringes til 62°C og holdes på dette nivå. In an autoclave of 500 1 of the same type as described in example 1, after prior blowing out of oxygen using 10 kg of vinyl chloride monomer, 100 kg of monomer and 16 g of azodiisobutyronitrile catalyst are introduced, i.e. a percentage of 0.016 in relation to the charged mono. ner.. The speed of the frame agitator is regulated to 100 revolutions per minute. The temperature of the mixture is brought to 62°C and maintained at this level.
Etter 3 timers for-polymerisering, innfores 100 kg vinylkloridmonomer samt 16 g azodiisobutyronitril. Rorerens hastighet reguleres til 30 omdreininger pr. minutt og holdes på denne verdi under annet polymerisasjonstrinn, hvilket vil si i 13 timer. Ikke polymerisert monomer fraskilles derpå den dannede polymer. Etter After 3 hours of pre-polymerisation, 100 kg of vinyl chloride monomer and 16 g of azodiisobutyronitrile are introduced. The speed of the rudder is regulated to 30 revolutions per minute and is kept at this value during the second polymerization stage, which means for 13 hours. Unpolymerized monomer is then separated from the formed polymer. After
tomning av autoklaven, finner man et utbytte på 69,5 i° Iregnet på emptying the autoclave, one finds a yield of 69.5 i° Calculated on
den monomere, i form av en pulverformig polymer med tilsynelatende egenvekt 0,57 og K-indeks ifolge Fikentscher lik 62. the monomeric, in the form of a powdery polymer with an apparent specific gravity of 0.57 and a K-index according to Fikentscher equal to 62.
Storrelsesf ordelingen fremgår av nedenstående1 tabell II. The size distribution is shown in table II below1.
Man finner at den fremstilte polymer har en meget' sammen-trengt storrelsesfordeling som er en del forbedret i forhold til i It is found that the produced polymer has a very narrow size distribution which is somewhat improved compared to in
produktet fra eksempel 1. the product from example 1.
Man vil se at 89 i° av partiklene har storrelser på You will see that 89% of the particles have sizes of
under 200 mikron og 74 $ av partiklene har storrelser som ligger mellom 100 og 160 mikron. below 200 microns and 74% of the particles have sizes between 100 and 160 microns.
Eksempel III Example III
Dette eksempel beskriver likeledes et foretrukket ut-forelseseksempel i henhold til oppfinnelsen. Det forste polymerisasjonstrinn utfores med en monomermengde lik l/3 av den totale monomermengde satset. Den anvendte apparatur er av samme typen som beskrevet i eksempel 1. This example also describes a preferred embodiment according to the invention. The first polymerization step is carried out with a monomer quantity equal to 1/3 of the total monomer quantity charged. The equipment used is of the same type as described in example 1.
I polymerisatoren innfores 70 kg vinylkloridmonomer etter forutgående avgassing av oksygenet med 7 kg monomer. Man innforer likeledes 11,2 g eller 0,016 % azodiisobutyronitril. Rorehastigheten reguleres til 100 omdreininger pr. minutt, temperaturen til 62°C og trykket folger da lik 9,3 ato. 70 kg of vinyl chloride monomer are introduced into the polymeriser after prior degassing of the oxygen with 7 kg of monomer. 11.2 g or 0.016% of azodiisobutyronitrile are also introduced. The rudder speed is regulated to 100 revolutions per minute, the temperature to 62°C and the pressure then equal to 9.3 ato.
Etter 3 timers polymerisasjon i forste trinn innfores After 3 hours of polymerisation in the first stage, it is introduced
140 kg vinylklorid og polymer-vinylklorid-blandingen tilsettes videre 22,4 g azodiisobutyronitril. Rbrehastigheten ^reguleres til 30 omdreininger pr. minutt og temperaturen holdes på 62°C. 140 kg of vinyl chloride and 22.4 g of azodiisobutyronitrile are added to the polymer-vinyl chloride mixture. The rotation speed is regulated to 30 revolutions per minute and the temperature is kept at 62°C.
Varigheten av etter-polymeriseringen, eller annet trinn, er 13 timer og 30 minutter, hvilket tilsvarer en total polymerisa-sjonstid på 16,5 timer. The duration of the post-polymerization, or second step, is 13 hours and 30 minutes, which corresponds to a total polymerization time of 16.5 hours.
Man får et utbytte på 67,3 f°, i form av en pulverformig polymer med K-indeks ifolge Fikentscher lik 62. Tilsynelatende egenvekt er 0,54. A yield of 67.3 f° is obtained, in the form of a powdery polymer with a K index according to Fikentscher equal to 62. Apparent specific gravity is 0.54.
Storrelsesfordelingen på den fremstilte polymer finnes The size distribution of the produced polymer is found
av nedenstående tabell III. of table III below.
Hvis man sammenligner resultatene fra eksempel 1, II og III,kan man konstatere: på den ene side at den polymeres tilsynelatende egenvekt ifolge eksempel III er ganske lite lavere enn egenvekten i henhold til eksemplene I og II, og på den annen side at storrelsesf ordelingen ifolge eksempel III er noe bredere. 80 fo If one compares the results from examples 1, II and III, it can be stated: on the one hand that the apparent specific gravity of the polymer according to example III is quite a bit lower than the specific gravity according to examples I and II, and on the other hand that the size distribution according to example III is somewhat wider. 80 fo
av partiklene har storrelser på under 200 mikron. of the particles have sizes of less than 200 microns.
Eksempel IV Example IV
I dette eksempel beskrives en utforelse i en apparatur med stor kapasitet, idet man anvender et katalysatorpar, nemlig en raskt dekomponerende katalysator for forste trinn og en langsomt dekomponerende katalysator for annet polymerisasjonstrinn. Forste polymerisasjonstrinn utfores med en monomermengde som er lik l/2-parten av den totale satsede mengde. This example describes an embodiment in an apparatus with a large capacity, using a pair of catalysts, namely a rapidly decomposing catalyst for the first stage and a slowly decomposing catalyst for the second polymerization stage. The first polymerization step is carried out with an amount of monomer equal to 1/2 of the total amount used.
I en fast horisontal autoklav med 12 m^ kapasitet, utstyrt med dobbelt ramme-roreverk, innfores etter vanlig utgassing ved hjelp av 300 kg vinylkloridmonomer 3000 kg av denne monomer samt 166,5 g, eller 0,0004 $ beregnet på aktivt oksygen av acetyl-cykloheksansulfonyl-peroksyd som katalysator. Rorerens omdrei-ningshastighet reguleres til 40 i minuttet, temperaturen holdes på 62°C og trykket blir da 9,3 ato i autoklaven. In a fixed horizontal autoclave with a capacity of 12 m^, equipped with a double frame agitator, after normal degassing using 300 kg of vinyl chloride monomer, 3000 kg of this monomer and 166.5 g, or $0.0004 calculated for active oxygen of acetyl, are introduced -cyclohexanesulfonyl peroxide as catalyst. The speed of rotation of the stirrer is regulated to 40 per minute, the temperature is kept at 62°C and the pressure then becomes 9.3 ato in the autoclave.
Etter 1 time og 15 minutter er omsetningsgraden omkring 10 og blandingen monomer/polymer går da over til en latent tilstand på grunn av at katalysatoren er oppbrukt eller brutt ned. After 1 hour and 15 minutes, the degree of conversion is around 10 and the monomer/polymer mixture then goes into a latent state due to the catalyst being used up or broken down.
Derpå innfores 3000 kg vinylkloridmonomer samt 1200 g azodiisobutyronitril som langsomt dekomponerende katalysator for annet trinns polymerisasjon. Rorehastigheten reguleres til 5 omdreininger pr. minutt. Dette annet polymerisasjonstrinn varer 10 timer og 15 minutter, tilsvarende en total reaksjonstid på 3,000 kg of vinyl chloride monomer and 1,200 g of azodiisobutyronitrile are then introduced as slowly decomposing catalyst for the second stage polymerization. The rudder speed is regulated to 5 revolutions per minute. This second polymerization step lasts 10 hours and 15 minutes, corresponding to a total reaction time of
11 timer og 30 minutter. 11 hours and 30 minutes.
Etter at polymerisasjonen er fullendt utfores avgassing og man fraskiller den dannede polymer fra ureagert monomer. Man får i et utbytte på 68,2 i° en pulverformig polymer med K-indeks ifolge Fikentscher lik 62 og tilsynelatende egenvekt på 0,56. After the polymerization is complete, degassing is carried out and the formed polymer is separated from unreacted monomer. A pulverulent polymer with a K index according to Fikentscher equal to 62 and an apparent specific gravity of 0.56 is obtained in a yield of 68.2 in°.
Storrelsesfordelingen finnes av nedenstående tabell IV. The size distribution can be found in table IV below.
Som tidligere er det for hver ny maskevidde (maske-åpning) uttrykt i mikron oppfort den .kumulative prosentdel som går gjennom sikten. As before, for each new mesh size (mesh opening) expressed in microns, the cumulative percentage passing through the sieve is increased.
Hvis man sammenligner resultatene fra eksemplene 1, Comparing the results from Examples 1,
II, III og IV kan man konstatere: for en total omsetningsgrad av omtrent samme storrelse er den totale reaksjonstid lavere når man anvender et katalysatorpar som i eksempel IV, den polymeres storrelsesf ordeling er snevrere. 90 $ av partiklene har storrelser på under 200 mikron og 70 $ av partiklene har storrelser på mellom 100 og 160 mikron. II, III and IV it can be noted: for a total degree of conversion of approximately the same size, the total reaction time is lower when using a catalyst pair as in example IV, the size distribution of the polymer is narrower. 90$ of the particles have sizes of less than 200 microns and 70$ of the particles have sizes of between 100 and 160 microns.
Eksempel V Example V
Man skal her beskrive en kopolymerisasjonsprosess i henhold til oppfinnelsen, idet forste polymerisasjonstrinn utfores med en monomermengde som tilsvarer 12-parten av den totale mengde som skal anvendes. A copolymerization process according to the invention will be described here, the first polymerization step being carried out with an amount of monomer corresponding to 12th of the total amount to be used.
I en fast horisontal autoklav utfort i rustfritt stål In a fixed horizontal autoclave constructed in stainless steel
og med 500 1 volum, utstyrt med delt rammerorer innfores 95 kg (95 i°) vinylklorid, 5 kg (5 i°) vinylacetat og 5,55 g acetylcyklo-heksansulf ony l-p er oksyd, eller 0,0004 i° beregnet som aktivt oksygen i forhold til komonomer-sammensetningen. and with 500 1 volume, equipped with split frame agitators, 95 kg (95 i°) of vinyl chloride, 5 kg (5 i°) of vinyl acetate and 5.55 g of acetylcyclohexanesulfony l-p are oxide are introduced, or 0.0004 i° calculated as active oxygen in relation to the comonomer composition.
Autoklaven er på forhånd gjennomblåst med 10 kg vinylklorid. The autoclave is previously blown through with 10 kg of vinyl chloride.
Temperaturen, bringes raskt til 62°C og holdes på denne temperatur, tilsvarende et trykk på 9,3 ato. Rorerens omdreinings-hastighet reguleres til 100 omdreininger pr. minutt. The temperature is quickly brought to 62°C and maintained at this temperature, corresponding to a pressure of 9.3 ato. The speed of rotation of the rudder is regulated to 100 revolutions per minute.
Etter 1 time og 15 minutter i forste polymerisasjonstrinn, har blandingen komonomer/kopolymer oppnådd en praktisk talt latent tilstand. Derpå innfores 40 g azodiisobutyronitril som langsomt dekomponerende katalysator (tilsvarende 0,02 i°) samtidig med 95 kg vinylkloridmonomer og 5 kg vinylacetat. Rorerens hastighet reguleres til 30 omdreininger pr. minutt. Temperaturen bringes opp til 62°C og holdes på dette nivå i annet trinn, i lopet av 10 timer og 30 minutter, hvilket gir en total reaksjonstid på 11 timer og 45 minutter. After 1 hour and 15 minutes in the first polymerization step, the comonomer/copolymer mixture has reached a practically latent state. 40 g of azodiisobutyronitrile are then introduced as slowly decomposing catalyst (corresponding to 0.02 i°) simultaneously with 95 kg of vinyl chloride monomer and 5 kg of vinyl acetate. The speed of the rudder is regulated to 30 revolutions per minute. The temperature is brought up to 62°C and maintained at this level in the second stage, over the course of 10 hours and 30 minutes, giving a total reaction time of 11 hours and 45 minutes.
Etter utgassing og fraskilling av komonomer får man i et utbytte på 74,2 " f° en kopolymer med tilsynelatende egenvekt på 0,67, og med en storrelsesfordeling som er gitt i tabell V nedenfor, After outgassing and separation of comonomers, a copolymer with an apparent specific gravity of 0.67 is obtained in a yield of 74.2 "f°, and with a size distribution given in table V below,
samt en K-indeks ifolge Fikentscher på 56. as well as a K-index according to Fikentscher of 56.
Man ser at 82 ?£ av partiklene har dimensjoner på under 200 mikron, og at 58 $ av partiklene har storrelser på mellom 100 og 160 mikron. It is seen that 82 ?£ of the particles have dimensions of less than 200 microns, and that 58 $ of the particles have sizes of between 100 and 160 microns.
Claims (1)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US29190781A | 1981-08-11 | 1981-08-11 | |
| US31986381A | 1981-11-09 | 1981-11-09 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO822722L NO822722L (en) | 1983-02-14 |
| NO161558B true NO161558B (en) | 1989-05-22 |
| NO161558C NO161558C (en) | 1989-08-30 |
Family
ID=26967047
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO822722A NO161558C (en) | 1981-08-11 | 1982-08-10 | ANALOGY PROCEDURE FOR THE PREPARATION OF ANTIHYPERTENSIVE BENZAZEPIN-2-ONER. |
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| KR (3) | KR890003425B1 (en) |
| AR (3) | AR240806A1 (en) |
| AT (1) | ATE18397T1 (en) |
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| CY (1) | CY1403A (en) |
| DD (1) | DD202546A5 (en) |
| DE (1) | DE3269625D1 (en) |
| DK (1) | DK157881C (en) |
| ES (6) | ES8502974A1 (en) |
| FI (1) | FI76074C (en) |
| GB (1) | GB2103614B (en) |
| GR (1) | GR77256B (en) |
| HK (1) | HK93387A (en) |
| HU (1) | HU189628B (en) |
| IE (1) | IE53668B1 (en) |
| IL (1) | IL66501A (en) |
| NL (1) | NL930112I2 (en) |
| NO (1) | NO161558C (en) |
| NZ (1) | NZ201555A (en) |
| PT (1) | PT75395B (en) |
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| US4473575A (en) * | 1982-07-19 | 1984-09-25 | Ciba-Geigy Corporation | 3-Amino-(1)-benzazepin-2-one-1-alkanoic acids |
| DE3373469D1 (en) * | 1982-09-30 | 1987-10-15 | Merck & Co Inc | 1-n-alkylcarboxy-benzofused lactams useful as antihypertensive agents |
| US4575503A (en) * | 1983-02-10 | 1986-03-11 | Ciba-Geigy Corporation | 3-Amino-[1]-benzazepin-2-one-1-alkanoic acids |
| US4564612A (en) * | 1983-04-22 | 1986-01-14 | Takeda Chemical Industries, Ltd. | Condensed, seven-membered ring compounds and their use |
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| JPS608284A (en) * | 1983-06-29 | 1985-01-17 | Mitsui Toatsu Chem Inc | Benzothiazepine derivative and its preparation |
| US4638000A (en) * | 1983-08-12 | 1987-01-20 | Takeda Chemical Industries, Ltd. | Condensed seven-membered ring compounds, their production and use |
| AU570710B2 (en) * | 1983-08-12 | 1988-03-24 | Takeda Chemical Industries Ltd. | 4-oxo-2, 3, 4, 5-tetrahydro-1, 5-benzoxazepine derivatives |
| IL72523A (en) * | 1983-08-12 | 1988-06-30 | Takeda Chemical Industries Ltd | 3-amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine derivatives,their production and pharmaceutical compositions containing them |
| EP0166354B1 (en) * | 1984-06-26 | 1992-08-05 | Merck & Co. Inc. | Benzofused lactam compounds and pharmaceutical compositions containing them |
| CA1266647A (en) * | 1984-06-26 | 1990-03-13 | William H. Parsons | Benzofused lactams useful as antihypertensive agents and as cholecystokinin antagonists |
| EP0166357A3 (en) * | 1984-06-26 | 1988-10-26 | Merck & Co. Inc. | Benzofused lactams and pharmaceutical compositions containing them |
| US4785089A (en) * | 1985-06-13 | 1988-11-15 | Ciba-Geigy Corporation | Novel sulfonic acid esters and their preparation |
| DE3704661A1 (en) * | 1987-02-14 | 1988-08-25 | Hoechst Ag | FELECTED AZEPINONE AND AZOCINONE DERIVATIVES, METHOD FOR THE PRODUCTION THEREOF, THEIR CONTAINERS AND THEIR USE, AND INTERMEDIATE PRODUCTS IN THEIR PRODUCTION |
| EP0322779A3 (en) * | 1987-12-29 | 1991-05-08 | Yoshitomi Pharmaceutical Industries, Ltd. | Benzolactam compounds and pharmaceutical uses thereof |
| TW197945B (en) * | 1990-11-27 | 1993-01-11 | Hoechst Ag | |
| GB9100028D0 (en) * | 1991-01-02 | 1991-02-20 | Ici Plc | Compounds |
| GB9212308D0 (en) * | 1992-06-10 | 1992-07-22 | Ici Plc | Therapeutic compositions |
| US5504080A (en) * | 1992-10-28 | 1996-04-02 | Bristol-Myers Squibb Co. | Benzo-fused lactams |
| CA2151384A1 (en) * | 1992-12-11 | 1994-06-23 | Peter Buhlmayer | Benzazepinone derivatives |
| GB9310075D0 (en) * | 1993-05-17 | 1993-06-30 | Fujisawa Pharmaceutical Co | New mercapto-amide derivatives,processes for the preparation thereof and pharmaceutical composition comprising the same |
| GB9311948D0 (en) * | 1993-06-10 | 1993-07-28 | Zeneca Ltd | Substituted nitrogen heterocycles |
| US5801168A (en) * | 1994-06-09 | 1998-09-01 | Zeneca Limited | Substituted nitrogen heterocycles |
| US5597922A (en) * | 1994-07-29 | 1997-01-28 | State Of Oregon, Acting By And Through The Oregon State Board Of Higher Education, Acting For And On Behalf Of The Oregon Health Sciences University And The University Of Oregon | Glycine receptor antagonist pharmacophore |
| EP1229913A4 (en) * | 1999-11-18 | 2005-01-19 | Antexpharma Inc | Substituted 1-benzazepines and derivatives thereof |
| US7053211B2 (en) | 2000-12-27 | 2006-05-30 | Merck Patent Gmbh | Process for the preparation of α-aminosubstituted carboxylic acid amides |
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| US7459474B2 (en) | 2003-06-11 | 2008-12-02 | Bristol-Myers Squibb Company | Modulators of the glucocorticoid receptor and method |
| US8080579B2 (en) | 2005-10-03 | 2011-12-20 | The Regents Of The University Of Michigan | Compositions and methods for treatment of inflammatory bowel disease |
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| US8034782B2 (en) | 2008-07-16 | 2011-10-11 | Synergy Pharmaceuticals, Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders |
| US8969514B2 (en) | 2007-06-04 | 2015-03-03 | Synergy Pharmaceuticals, Inc. | Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases |
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| EP2810951B1 (en) | 2008-06-04 | 2017-03-15 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders |
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| CN105764916B (en) | 2013-06-05 | 2021-05-18 | 博士医疗爱尔兰有限公司 | Ultrapure agonists of guanylate cyclase C, methods of making and using the same |
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| US3395150A (en) * | 1965-02-26 | 1968-07-30 | Squibb & Sons Inc | Benzothiazepine carboxamides and derivatives thereof |
| GB1305278A (en) * | 1970-03-12 | 1973-01-31 |
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1982
- 1982-08-05 EP EP82810329A patent/EP0072352B1/en not_active Expired
- 1982-08-05 GB GB08222564A patent/GB2103614B/en not_active Expired
- 1982-08-05 DE DE8282810329T patent/DE3269625D1/en not_active Expired
- 1982-08-05 CY CY140382A patent/CY1403A/en unknown
- 1982-08-05 AT AT82810329T patent/ATE18397T1/en active
- 1982-08-09 IL IL66501A patent/IL66501A/en not_active IP Right Cessation
- 1982-08-09 ES ES514856A patent/ES8502974A1/en not_active Expired
- 1982-08-09 GR GR68996A patent/GR77256B/el unknown
- 1982-08-09 FI FI822770A patent/FI76074C/en not_active IP Right Cessation
- 1982-08-09 CA CA000409019A patent/CA1196636A/en not_active Expired
- 1982-08-09 PT PT75395A patent/PT75395B/en unknown
- 1982-08-10 DK DK358682A patent/DK157881C/en active
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- 1982-08-10 AU AU87014/82A patent/AU561395B2/en not_active Expired
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- 1982-08-10 DD DD82242400A patent/DD202546A5/en not_active IP Right Cessation
- 1982-08-10 NZ NZ201555A patent/NZ201555A/en unknown
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- 1982-08-11 AR AR290295A patent/AR240806A1/en active
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1983
- 1983-10-28 ES ES526888A patent/ES8504728A1/en not_active Expired
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- 1983-10-28 ES ES526887A patent/ES8606285A1/en not_active Expired
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1984
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1989
- 1989-05-13 KR KR8906486A patent/KR900001190B1/en not_active Expired
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1993
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