CA1129886A - Process for the preparation of n-alkylaminobenzophenones - Google Patents
Process for the preparation of n-alkylaminobenzophenonesInfo
- Publication number
- CA1129886A CA1129886A CA335,380A CA335380A CA1129886A CA 1129886 A CA1129886 A CA 1129886A CA 335380 A CA335380 A CA 335380A CA 1129886 A CA1129886 A CA 1129886A
- Authority
- CA
- Canada
- Prior art keywords
- quaternary ammonium
- preparation
- ammonium derivative
- general formula
- benzophenone
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B61/00—Other general methods
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C1/00—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/02—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions involving the formation of amino groups from compounds containing hydroxy groups or etherified or esterified hydroxy groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C221/00—Preparation of compounds containing amino groups and doubly-bound oxygen atoms bound to the same carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C225/00—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones
- C07C225/22—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones having amino groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/02—Preparation of carboxylic acid amides from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
Procédé de préparation de N-alcoylamino benzophénones PIERRE FABRE S.A. Invention de : G. MOUZIN et H. COUSSE La présente invention concerne un nouveau procédé de préparation de N-alcoylamino benzophénones. Pour la préparation de N-alcoylamino benzophénones répondant à la formule générale I (I) dans laquelle: R représente un groupe alcoyle inférieur en C1 à C5 à chaîne linéaire ou ramifiée, et chacun des deux symboles X représente, indépendamment de l'autre, un atome d'hydrogène ou un atome d'halogène, on fait réagir selon l'invention une amino benzophénone de formule générale II (II) dans laquelle les symboles X ont les significations ci-dessus avec un agent d'alcoylation en présence d'une base et d'un catalyseur constitué par un dérivé d'ammonium quaternaire, au sein d'un solvant organique. Application à la préparation de médicaments, tels que les dérivés de benzoyl-2 chloro-4 glycinanilides.Process for the preparation of N-alkylamino benzophenones PIERRE FABRE S.A. Invention by: G. MOUZIN and H. COUSSE The present invention relates to a new process for the preparation of N-alkylamino benzophenones. For the preparation of N-alkylamino benzophenones corresponding to the general formula I (I) in which: R represents a lower C1-C5 alkyl group with straight or branched chain, and each of the two symbols X represents, independently of the other, a hydrogen atom or a halogen atom, an amino benzophenone of general formula II (II) is reacted according to the invention in which the symbols X have the meanings above with an alkylating agent in the presence of a base and a catalyst consisting of a quaternary ammonium derivative, within an organic solvent. Application to the preparation of medicaments, such as derivatives of 2-benzoyl-4-chloro-glycinanilides.
Description
La présente invention concerne un nouveau procédé
de préparation de N-alcoylamino benzophénones répondant à la formule générale I
R
~ ~- H
X = O
dans laquelle:
R représente un groupe alcoyle inférieur en Cl à C5 à
chaîne linéaire ou ramifiée, et chacun des deux symboles X représente; indépendamment de l'autre, un atome d'hydrogène ou un atome d'halogène, par alcoylation sélective et quantitative d'amino benzophénones correspondantes.
Les procédés de préparation de N-alcoylamino benzophénones à partir d'amino benzophénones ou de leurs dérivés, qui ont été proposés antérieurement sont les suivants: -1/ Procédé Sternbach (L.H.STER~BACH, R.Ian FRYER, W.METLESICS, G.SACH et A.STEMPEL- J. Org. Chem. 27,3781, 1962).
Ce procédé antérieur consiste à effectuer une tosylation de l'amino benzophénone, une alcoylation du sulfamide intermédiaire et une hydrolyse par l'acide -;A
sulfurique concentré selon le schéma réactionnel:
~!
, ' . . . :
~ ;
1~?~5~8~
~H2 ClS02~C I~ ~ ~3 -- x~=o ~.1~, c=o --D
X ~ X
CH
<~ ~ SO ~1~' ,/1 ~ 3,X
... .
. The present invention relates to a new process for the preparation of N-alkylamino benzophenones responding to the general formula I
R
~ ~ - H
X = O
in which:
R represents a lower C1 to C5 alkyl group at linear or branched chain, and each of the two symbols X represents; independently of the other, a hydrogen atom or a halogen atom, by selective and quantitative amino alkylation corresponding benzophenones.
The processes for preparing N-alkylamino benzophenones from amino benzophenones or their derivatives, which have been proposed previously are the following: -1 / Sternbach process (LHSTER ~ BACH, R.Ian FRYER, W. METLESICS, G.SACH and A.STEMPEL- J. Org. Chem. 27.3781, 1962).
This prior method consists in performing a tosylation of the amino benzophenone, an alkylation of the intermediate sulfonamide and acid hydrolysis -; A
concentrated sulfuric according to the reaction scheme:
~!
, '. . . :
~;
1 ~? ~ 5 ~ 8 ~
~ H2 ClS02 ~ CI ~ ~ ~ 3 - x ~ = o ~ .1 ~, c = o --D
X ~ X
CH
<~ ~ N / A ~ 1 ~ ' , / 1 ~ 3, X
...
.
2/ Procédé par benzoylation . Ce procédé antérieur décrit dans le brevet US n 2 / Benzoylation process . This prior process described in US patent n
3,886,208 est mis an oeuvre selon le schéma réactionnel suivant:
~ 2 --~ ~ o ~H2 / ~ ~ H-C ~ SO4Me2 =O X --O
~X ~X
. CH3 I~IT C ~SaPOn1~1Cat~IC-HI3I
x =o . =o ~3~X ~,,X
3/ Procédé Podesva (C.PODESVA, C. SOLOMON et K.VAGI - Can. J. Chem. 46, 435, ~j~
1968).
Conformément à ce procedé on traite l'amino benzophénone en solution dans l'acide acétique par du sulfate de méthyle, ce qui conduit à un mélange de 3 produits :
l'amino benzophénone, la N-méthyl-amino ben~ophénone et la diméthyl amino benzophénone selon le schéma réactionnel:
~, . , ~. :
fi ` f~3 NH2 X~L o X ~; _0 ~4(~e)2 ¦ X~3~._ La séparation de ces amines est délicate et l'amine secondaire n'est obtenue qu'avec un faible rendement. 3,886,208 is used according to the reaction scheme following:
~ 2 -~ ~ o ~ H2 / ~ ~ HC ~ SO4Me2 = OX --O
~ X ~ X
. CH3 I ~ IT C ~ SaPOn1 ~ 1Cat ~ IC-HI3I
x = o. = o ~ 3 ~ X ~ ,, X
3 / Podesva process (C. PODESVA, C. SOLOMON and K. VAGI - Can. J. Chem. 46, 435, ~ j ~
1968).
In accordance with this process we treat the amino benzophenone dissolved in acetic acid by sulfate methyl, which leads to a mixture of 3 products:
amino benzophenone, N-methyl-amino ben ~ ophenone and dimethyl amino benzophenone according to the reaction scheme:
~,. , ~. :
fi `f ~ 3 NH2 X ~ L o X ~; _0 ~ 4 (~ e) 2 ¦ X ~ 3 ~ ._ The separation of these amines is delicate and the amine secondary is only obtained with a low yield.
4/ Procédé au formaldéhyde (L.H.STERNBACH, R.Ian FRYER, W.METLESICS, G.SACH et A.STEMPEL- J. Org. Chem. 27, 3781 (1962).
~ 4 -~ .. ..
~ . .
8~
L'amino benzophénone traitée par un excès de formaldéhyde conduit au produit diméthylé ; en utilisant un défaut de formaldehyde on obtient comme dans le cas précédent un mélange de produits difficilement purifiable.
Tous ces procédés antérieurs présentent les inconvénients majeurs suivants:
- le nombre des étapes et/ou la non sélectivité qui conduit à des composés diméthylés, et - le rendement global en produit purifié reste toujours faible.
Le procédé selon la présente invention vise précisément à pallier ces lnconvénients et permet donc d'obtenir quantitativement en une seule étape des N-alcoylamino benzophénones pures.
Conformément à la présente invention, on alcoyle sélectivement et quantitativement une amino benzophénone de formule générale II
~ NH2 ` 1- 11 - "~"~
~, ~ ~ C=O (II) ~ ` ~
dans laquelle chacun des deux symboles X représente, indépendamment de l'autre, un atome d'hydrogène ou un atome d'halogène, à l'aide d'un agent d'alcoylation en présence d'une base et d'une dérivé d'ammonium quaternaire utilisé
comme catalyseur au sein d'un solvant organique.
~ 5 ~
: ; `
Selon une autre caractéristique de la présen-te `~
invention, le catalyseur additionné au milieu réactionnel est constitué par un dérivé d'ammonium quaternaire de formule générale R' dans laquelle R' représente un groupe alcoyle, tel que par exemple un radical butyle, et X représente un atome d'halogène. A titre d'exemple particulier de catalyseur on citera le bromure de tétrabutylammonium (BTBA~.
Selon le procédé de l'inveniton le catalyseur est introduit dans le milieu réactionnel à raison d'environ 0,01 à 0,5 mole, de préférence d'environ 0,1 mole, par mole d'amino benzophénone de départ.
La réaction de N-alcoylation sélective selon la présente invention peut être schématisée de la fa~on suivante:
X ~ \CNoH
or~,anlque [~X ~X
les symboles R et X ayant les significations indiquées précédemment.
La présen-te invention se rapporte également aux N-alcoyl-amino benzophénone de formule générale I obtenue par la mise en oeuvre du procédé, ainsi qu'à leur application en tant qu'intermédiaires de synthèse intervenant dans la préparation de composés utiles comme médicaments, et plus particulièrement le diazepam et les dérivés de benzoyl-2 chloro-~ glycinanilides (brevet francais n 77 18511, n de publication 2,403,330).
Le procéde de la présente invention sera illustré
ci-après à l'aide des quelques exemples non limitatifs suivants:
Exemple 1: Méthylamino-2 chloro-5 benzophénone A une solution de 231 g d'amino-2 chloro-5 benzophénone (1 mole) et 0,1 mole de bromure de tétrabutylammonium dans 2 litres de tétrahydrofuranne, on ajoute 160 g de soude en poudre (4 moles). On agite 5 `~-``
minutes à température ambiante, puis on additionne 3 moles de sulfate de méthyle et on porte le mélange réactionnel à 60C
pendan-t environ 1 heure. Après évaporation du solvant jusqu'à siccité, on reprend le résidu dans l'acétate d'éthyle, on lave à l'eau jusqu'à neutralité, on sèche sur sulfate de sodium, on filtre et on évapore le solvant.
On récupère ainsi quantitativement le produit de formule:
f ~
~ ~ " N
C~ / ~ C'=O
~ - 7 -~ . 1 11 :, formule brute: C14H12Cl N 0 masse moléculaire: 245,71 Point de fusion: 95C
chromatographie sur plaque:
- support: gel de silice 60 F 254 Merck*
- solvant: acétate d'éthyle/éther de pétrole 10/90 - révélation: UV et iode - Rf: 0,38 Exemple 2: Ethylamino-2 chloro-5 benzophénone D'une manière analogue à celle décrite dans l'exemple 1, mais en utilisant le sulfate d'éthyle comme agent d'alcoylation, on obtient le produit de formule:
* marque de commerce - 7a -. ' ' " ~
- : , .: , ~ 13L~8~
CH2~CH~
N-H
~1 C-O
1 0 V ~
.formule brute : C15H.I4 Cl M 0 _ ~.
~asse moléculaire : 259,74 Point de fusion : 56C
chroMatographie sur plaque :
~ SUppOI`-t : ~el de silice 60 F 254 Merck - sol~an'c : acetate d'éthyle - éther de petrole 10/90 - révélation : W et iode ~ 0~55 20 Exempl~ 3 ~léthylalnino -2 dichloro-2~-5 benzophénone _______ _ .
Dltme rnanière analogue .à celle.déGrite dans l'exemp1e 1 mais en u+iiisant l'a~i.no-2 dichloro-2l-5 benzoph~none, cn obtient le produit de t'orrnule:
~5 TF~3 ~ f~ ~ N-H
3~ C~J ~ ~ _0 ~ ~ Cl .. '~ . .
formule brute : C14H11C12 N O
masse moléculaire : 280,16 Cristaux jaune d'or Point de fusion : 89C
chromatographie sur plaque :
- support : gel de silice 60 F 254 Merck - solvant ~: acétate d'éthyle - éther de pétrole 10/90 - révélation : UV et iode - Rf : 0,53 Exemple 4 : Méthylamino-2 fluoro-2' chloro-5 benzophénone D'une manière analogue à celle décrite dans l'exemple 1, mais en utilisant l'amino-2 fluoro-2' chloro-5 benzophénone, on obtient le produit de formule :
fH3 N-~E
Cl ~ ~ C=0 , F
l .
formule brute : C14HllCl F N O
masse mol'eculaire : 263,7 , 1~', .
.. ~., j; I .
- ~
; ' , . 4 / formaldehyde process (LHSTERNBACH, R.Ian FRYER, W. METLESICS, G.SACH and A.STEMPEL- J. Org. Chem. 27, 3781 (1962).
~ 4 -~ .. ..
~. .
8 ~
The amino benzophenone treated with an excess of formaldehyde leads to the dimethylated product; using a defect in formaldehyde we obtain as in the previous case a mixture of products that is difficult to purify.
All of these prior processes present the following major drawbacks:
- the number of stages and / or the non-selectivity which leads to dimethyl compounds, and - the overall yield of purified product remains always weak.
The method according to the present invention aims precisely to overcome these drawbacks and therefore allows obtain quantitatively in a single step N-pure alkyl benzophenones.
In accordance with the present invention, we alkylate selectively and quantitatively an amino benzophenone of general formula II
~ NH2 `1- 11 -" ~ "~
~, ~ ~ C = O (II) ~ `~
in which each of the two symbols X represents, independently of the other, a hydrogen atom or an atom halogen, using an alkylating agent in the presence a base and a quaternary ammonium derivative used as a catalyst in an organic solvent.
~ 5 ~
:; ``
According to another characteristic of the present ``
invention, the catalyst added to the reaction medium is consisting of a quaternary ammonium derivative of formula general R ' in which R 'represents an alkyl group, such as by example a butyl radical, and X represents an atom halogen. As a particular example of a catalyst, cite tetrabutylammonium bromide (BTBA ~.
According to the process of the invention the catalyst is introduced into the reaction medium at a rate of approximately 0.01 0.5 mole, preferably about 0.1 mole, per mole starting amino benzophenone.
The selective N-alkylation reaction according to the present invention can be schematized in the fa ~ on next:
X ~ \ CNoH
gold ~, anlque [~ X ~ X
the symbols R and X having the meanings indicated previously.
The present invention also relates to N-alkylamino benzophenone of general formula I obtained by the implementation of the process, as well as their application in as synthetic intermediaries involved in the preparation of compounds useful as medicaments, and more particularly diazepam and benzoyl-2 derivatives chloro- ~ glycinanilides (French patent n 77 18511, n of publication 2,403,330).
The process of the present invention will be illustrated below using a few non-limiting examples following:
Example 1: 2-methylamino-5 chloro-benzophenone To a solution of 231 g of 2-chloro-5 amino benzophenone (1 mole) and 0.1 mole of bromide tetrabutylammonium in 2 liters of tetrahydrofuran, we add 160 g of sodium hydroxide powder (4 moles). Shake 5 '~ -``
minutes at room temperature, then add 3 moles of methyl sulfate and the reaction mixture is brought to 60C
hangs for about 1 hour. After evaporation of the solvent until dry, the residue is taken up in acetate ethyl, washed with water until neutral, dried on sodium sulfate, filtered and the solvent is evaporated.
We thus quantitatively recover the product of formula:
f ~
~ ~ "N
C ~ / ~ C '= O
~ - 7 -~. 1 11 :, raw formula: C14H12Cl N 0 molecular mass: 245.71 Melting point: 95C
plate chromatography:
- support: silica gel 60 F 254 Merck *
- solvent: ethyl acetate / petroleum ether 10/90 - revelation: UV and iodine - Rf: 0.38 EXAMPLE 2 Ethylamino-2 chloro-5 benzophenone In a manner analogous to that described in Example 1, but using ethyl sulfate as alkylating agent, the product of formula is obtained:
* trademark - 7a -. ''"~
-:, .:, ~ 13L ~ 8 ~
CH2 ~ CH ~
NH
~ 1 CO
1 0 V ~
.rough formula: C15H.I4 Cl M 0 _ ~.
~ molecular basis: 259.74 Melting point: 56C
plate chromatography:
~ SUPPORT`-t: ~ silica el 60 F 254 Merck - sol ~ an'c: ethyl acetate - petroleum ether 10/90 - revelation: W and iodine ~ 0 ~ 55 20 Example ~ 3 ~ lethylalnino -2 dichloro-2 ~ -5 benzophenone _______ _.
Similar term to that described in Example 1 but in u + iiisant a ~ i.no-2 dichloro-2l-5 benzoph ~ none, cn get the product of the cell:
~ 5 TF ~ 3 ~ f ~ ~ NH
3 ~ C ~ D ~ ~ _0 ~ ~ Cl .. '~. .
raw formula: C14H11C12 NO
molecular weight: 280.16 Golden yellow crystals Melting point: 89C
plate chromatography:
- support: silica gel 60 F 254 Merck - solvent ~: ethyl acetate - petroleum ether 10/90 - revelation: UV and iodine - Rf: 0.53 Example 4: 2-methylamino-2-fluoro-5-chloro-benzophenone In a manner analogous to that described in example 1, but using 2-amino-fluoro-2 'chloro-5 benzophenone, we obtain the product of formula:
fH3 N- ~ E
Cl ~ ~ C = 0 , F
l.
raw formula: C14HllCl FNO
molecular mass: 263.7 , 1 ~ ',.
.. ~., j; I.
- ~
; ',.
Claims (10)
(I) dans laquelle R représente un groupe alcoyle inférieur en C1 à C5 à chaîne linéaire ou ramifiée, et chacun des deux symboles X représente, indépendamment de l'autre, un atome d'hydrogène ou un atome d'halogène, caractérisé en ce que l'on fait réagir une amino benzophénone de formule générale II
(II) dans laquelle les symboles X ont les significations ci-dessus avec un agent d'alcoylation en présence d'une base et d'un catalyseur constitué par un dérivé d'ammonium quaternaire, au sein d'un solvant organique. 1. Process for the preparation of N-alkylamino benzophenones, having the general formula I
(I) in which R represents a lower C1 to C5 chain alkyl group linear or branched, and each of the two symbols X represents, independently of the other, a hydrogen atom or a halogen atom, characterized in that an amino benzophenone of general formula II
(II) in which the symbols X have the meanings above with an alkylating agent in the presence of a base and a catalyst consisting of a quaternary ammonium derivative, at within an organic solvent.
dans laquelle R' représente un groupe alcoyle, et X représente un atome d'halogène. 6. Method according to claim 1, characterized in that that the catalyst is a quaternary ammonium derivative of general formula:
in which R 'represents an alkyl group, and X represents a halogen atom.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR7826918 | 1978-09-20 | ||
FR7826918A FR2436774A1 (en) | 1978-09-20 | 1978-09-20 | N-Alkylamino-benzophenone preparation - by reacting amino-benzophenone with alkylation agent, base, quat. ammonium catalyst etc. to give pharmaceutical intermediate (J5 28.3.80) |
Publications (1)
Publication Number | Publication Date |
---|---|
CA1129886A true CA1129886A (en) | 1982-08-17 |
Family
ID=9212811
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA335,380A Expired CA1129886A (en) | 1978-09-20 | 1979-09-11 | Process for the preparation of n-alkylaminobenzophenones |
Country Status (5)
Country | Link |
---|---|
JP (1) | JPS5543099A (en) |
CA (1) | CA1129886A (en) |
ES (1) | ES484245A1 (en) |
FR (1) | FR2436774A1 (en) |
IT (1) | IT1162396B (en) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2436776A1 (en) * | 1978-09-25 | 1980-04-18 | Fabre Sa Pierre | NOVEL ORTHO CHLORO BENZOYL-2 CHLORO-4 GLYCYLANILIDE DERIVATIVES, THEIR PREPARATION AND THEIR APPLICATION AS MEDICAMENTS |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1285390A (en) * | 1969-12-23 | 1972-08-16 | Pharmacia Ab | Improvements in the n-alkylation of acylated amino compounds |
-
1978
- 1978-09-20 FR FR7826918A patent/FR2436774A1/en active Granted
-
1979
- 1979-09-11 CA CA335,380A patent/CA1129886A/en not_active Expired
- 1979-09-18 ES ES484245A patent/ES484245A1/en not_active Expired
- 1979-09-19 IT IT50292/79A patent/IT1162396B/en active
- 1979-09-20 JP JP12155679A patent/JPS5543099A/en active Pending
Also Published As
Publication number | Publication date |
---|---|
FR2436774B1 (en) | 1982-12-03 |
IT7950292A0 (en) | 1979-09-19 |
ES484245A1 (en) | 1980-05-16 |
JPS5543099A (en) | 1980-03-26 |
FR2436774A1 (en) | 1980-04-18 |
IT1162396B (en) | 1987-03-25 |
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