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US2557911A - Method of preparing glycocyamidines - Google Patents

Method of preparing glycocyamidines Download PDF

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Publication number
US2557911A
US2557911A US156933A US15693350A US2557911A US 2557911 A US2557911 A US 2557911A US 156933 A US156933 A US 156933A US 15693350 A US15693350 A US 15693350A US 2557911 A US2557911 A US 2557911A
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parts
preparing
acetone
sodium
octylglycocyamidine
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US156933A
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Erick I Hoegberg
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Wyeth Holdings LLC
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American Cyanamid Co
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D233/00Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/66Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D233/88Nitrogen atoms, e.g. allantoin

Definitions

  • R represents a member of the group consisting of alkyl and aryl radicals
  • R represents a member of the group consisting, of hydrogen, alkyl and aryl radicals, such as, for example, l-n-butylglycocyamidine, l-n-octylglycocyamidine, l-dodecylglycocyamidine, l-octadecylglycocyamidine, l-phenylglycocyamidine, 1, 3- diphenylglycocyamidine, l-phenyl 3 ethylglycocyamidine, l-phenyl-3-allyglycocyamidine, 1- phenyl-3-cyclohexylglycocyamidine, 1-phenyl-3- n-octylglycocyamidine, l-phenyls3
  • glycocyamidine of the above type maybe readily prepared by reacting an alkali-forming metal salt of. a monosubstituted cyanamide of the formula.
  • M is an alkali-forming metal
  • 2 is an integer not greater than 2 and R.
  • R has the meaning shown above, with a haloacetamide of the formula X-CHi in which X is a halogen and R has the meaning shown above, in the presence of a solvent.
  • alkali-forming metal as used in this specification and claims is intended to cover the alkali and alkaline earth metals.
  • solvents which may be employed in the presses are water, the low molecular Weight aliphatic monohyclric alcohols such as, for example, methyl, ethyl, isopropy1,n-propyl, n-butyl, tert.-buty1 and sec.-amyl alcohol; ketones such as acetone, methy ethyl ketone, methyl n-propyl ketone, methyl isobutyl ketone, methyl benzyl ketone, cyclohexanone, and acetophenone; alkyl esters ofaliphatic monocarboxylic' acids having boiling points less than 200 C.
  • the low molecular Weight aliphatic monohyclric alcohols such as, for example, methyl, ethyl, isopropy1,n-propyl, n-butyl, tert.-buty1 and sec.-amyl alcohol
  • ketones such as acetone, meth
  • n-capronitrile such as ethyl acetate, n-propyl acetate, n-butyl acetate, iso-butyl acetate, 2-ethylhexyl acetate, ethyl propionate, methyl butyrate and n-propyl valerate; aromatic nitriles and aliphatic saturated nitriles having boiling points not greater than 220 C. such as benzonitrile, acetonitrile, propionitrile, isobutyronitrile, and n-capronitrile.
  • the reaction is preferably carried out at a temperature within the range of from about 20 to 0.. However, temperatures outside of this range may be employed depending upon the type of reactants and solvents utilized.
  • Example 2 A mixture of 14 parts of sodium phenylcyanamide, 9.4 parts of chloroacetamide and 200 parts of acetone was heated to reflux for a period of 4 hours in a vessel equipped with a stirrer and refiux condenser. The mixture was cooled to room temperature and filtered. The filter cake was washed with water and then dried at 65 0., giving 9.1 parts of l-phenylglycocyamidine.
  • Example 3 Example 2 was repeated using 200 parts of acetonitrile in place of the acetone as the solvent for the reactants. 10.6 parts of l-phenylglycocyamidine were obtained.
  • Example 4 Example 2 was repeated using 200 parts of ethyl acetate in place of the acetone. 12.5 parts (71% yield) of l-phenylglycocyamidine were obtained.
  • Example 5 A mixture of 4.4 parts of sodium n-octylcyanamide, 2.4 parts of chloroacetamide and 100 parts of acetone was heated to reflux for three The acetone was distilled on and the residue was washed with water to remove the by-product sodium chloride. 3.12 parts of l-noctylglycocyamidine were obtained. After recrystallization from alcohol, the product was a colorless crystalline material melting at 239"- 244" C.
  • Example 6 A mixture of 14 parts of sodium phenylcyanamide, 25 parts of a-bromo-N-n-octylacetamide and 100 parts of ethyl alcohol was heated to reflux for two hours and then allowed to stand at room temperature for 16 hours. The reaction mixture was filtered to remove the precipitated sodium bromide. The filtrate was heated to distill off the ethyl alcohol. The residue was recrystallized twice from methyl alcohol, giving 8 parts of 1-phenyl-3-n-octylglycocyamidine, a colorless crystalline material melting at 3688 C.
  • Example 7 A mixture of 14 parts of sodium phenylcyanamide, 17 parts of a-chloroacetanilide and 300 parts of acetone was warmed on a steam bath for one hour, then allowed to stand at room temperature for 48 hours. The acetone was distilled off, and the residue was washed with water and dried at 65 C. 22 parts (87% yield) of 1,3-diphenylglycocyamidine were obtained. After recrystallization from acetone, the product was a colorless crystalline material melting at 164-l65 C.
  • Example 8 A mixture of 14 parts of sodium phenylcyanamide, 21.5 parts of a-chloro-p-nitroacetanilide and 150 parts of ethyl alcohol was heated to reflux for three hours and then allowed to stand at room temperature for 16 hours. The reaction mixture was filtered. The filter cake was washed with water and then dried, giving 23 parts (78% yield) of 1-pheny1-3-p-nitropheny1glycocyamidine. After recrystallization from acetone, the product was a yellow, crystallin material melting at 271-273 C.
  • Example 9 8.73 parts of sodium-p-chlorophenylcyanamide and 4.68 parts of chloroacetamide were dissolved in parts of water and allowed to stand at room temperature for 48 hours. The resulting precipitate was filtered, washed with water and dried at C. 7 parts (67% yield) of l-p-chlorophenylglycocyamidine were obtained. After recrystallization from acetone, the product was a tan-colored, crystalline material melting at 275-278 C. with decomposition.
  • glycocyamidines prepared by the methods of the present invention, are adapted for various uses, more particularly as chemotherapeutic agents, bactericides, and catalysts for the polymerization of unsaturated organic compounds to form high molecular weight linear polymers.
  • a method of preparing a glycocyamidine of the general formula wherein R represents a member of the group consisting of alkyl and aryl radicals, and R represents a member of the group consisting of hydrogen, alkyl and aryl radicals, which comprises reacting an alkali-forming metal salt of a monosubstituted cyanamide of the formula RN M a in which M is an alkali-forming metal, a is an integer not greater than 2 and R is a member of the group consisting of alkyl and aryl radicals, with a haloacetamide of the formula X-CH C O r sen in which X is a halogen and R is a member of the group consisting of hydrogen, alkyl and aryl radicals, in the presence of a solvent, and recovering the glycocyamidine.
  • a method of preparing l-phenylglycocyami- .dine which comprises reacting sodium phenylcyanamide withv chloroacetamide in the presence of a solvent, and recovering the 1-phenylglycocyamidine.
  • a method of preparing l-n-octylglycocyamidine which comprises reacting sodium n-octylcyanamide with chloroacetamide in the presence of a solvent, and recovering the l-n-octylglycocyamidine.
  • a method of preparing 1-phenyl-3-n-octylglycocyamidine which comprises reacting sodium phenylcyanamide with a-bromo-N-n-octylacetamide in the presence of a solvent, and recovering the 1-phenyl-3n-octylglycocyamidine.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Description

Patented June 19, 1951 UNITED STATES PATENT OFFICE METHOD OF PREPARING GLYCO- CYAMIDIN ES Erick I. Hoegberg, Stamford, Conn., assignor to American Cyanamid Company, New York, N. Y., a corporation of Maine No Drawing. Application April 19, 1950, Serial No. 156,933
I eral formula HN=O2 4 \i/ in which R represents a member of the group consisting of alkyl and aryl radicals, and R represents a member of the group consisting, of hydrogen, alkyl and aryl radicals, such as, for example, l-n-butylglycocyamidine, l-n-octylglycocyamidine, l-dodecylglycocyamidine, l-octadecylglycocyamidine, l-phenylglycocyamidine, 1, 3- diphenylglycocyamidine, l-phenyl 3 ethylglycocyamidine, l-phenyl-3-allyglycocyamidine, 1- phenyl-3-cyclohexylglycocyamidine, 1-phenyl-3- n-octylglycocyamidine, l-phenyls3-decylglycocyamidine, l-n-amyl-3-isopropylglycocyamidine, 1- n-octyl-3-n-buty1g1ycocyamidine, l-n-octyl 3 tetradecylglycocyamidine, 1 -n-butyl-3 -(1-naphthyD-glycocyamidine, and l (2 ethylheXy1)-3- phenylglycocyamidine.
It has been discovered that a glycocyamidine of the above type maybe readily prepared by reacting an alkali-forming metal salt of. a monosubstituted cyanamide of the formula.
in which M is an alkali-forming metal, 2 is an integer not greater than 2 and R. has the meaning shown above, with a haloacetamide of the formula X-CHi in which X is a halogen and R has the meaning shown above, in the presence of a solvent.
The term alkali-forming metal as used in this specification and claims is intended to cover the alkali and alkaline earth metals.
A typical reaction in which sodium phenylcyanamide is reacted with a-blOIl'lO-N-Il-OCtYlacetamide to produce 1-phenyl-3 n octylglycocyamidine may be illustrated as follows:
Typical examples of solvents which may be employed in the presses are water, the low molecular Weight aliphatic monohyclric alcohols such as, for example, methyl, ethyl, isopropy1,n-propyl, n-butyl, tert.-buty1 and sec.-amyl alcohol; ketones such as acetone, methy ethyl ketone, methyl n-propyl ketone, methyl isobutyl ketone, methyl benzyl ketone, cyclohexanone, and acetophenone; alkyl esters ofaliphatic monocarboxylic' acids having boiling points less than 200 C. such as ethyl acetate, n-propyl acetate, n-butyl acetate, iso-butyl acetate, 2-ethylhexyl acetate, ethyl propionate, methyl butyrate and n-propyl valerate; aromatic nitriles and aliphatic saturated nitriles having boiling points not greater than 220 C. such as benzonitrile, acetonitrile, propionitrile, isobutyronitrile, and n-capronitrile.
The reaction is preferably carried out at a temperature within the range of from about 20 to 0.. However, temperatures outside of this range may be employed depending upon the type of reactants and solvents utilized.
The invention is further illustrated by the following examples in-which the parts areby weight.
Example 1 hours.
Example 2 A mixture of 14 parts of sodium phenylcyanamide, 9.4 parts of chloroacetamide and 200 parts of acetone was heated to reflux for a period of 4 hours in a vessel equipped with a stirrer and refiux condenser. The mixture was cooled to room temperature and filtered. The filter cake was washed with water and then dried at 65 0., giving 9.1 parts of l-phenylglycocyamidine.
Example 3 Example 2 was repeated using 200 parts of acetonitrile in place of the acetone as the solvent for the reactants. 10.6 parts of l-phenylglycocyamidine were obtained.
Example 4 Example 2 was repeated using 200 parts of ethyl acetate in place of the acetone. 12.5 parts (71% yield) of l-phenylglycocyamidine were obtained.
Example 5 A mixture of 4.4 parts of sodium n-octylcyanamide, 2.4 parts of chloroacetamide and 100 parts of acetone was heated to reflux for three The acetone was distilled on and the residue was washed with water to remove the by-product sodium chloride. 3.12 parts of l-noctylglycocyamidine were obtained. After recrystallization from alcohol, the product was a colorless crystalline material melting at 239"- 244" C.
Example 6 A mixture of 14 parts of sodium phenylcyanamide, 25 parts of a-bromo-N-n-octylacetamide and 100 parts of ethyl alcohol was heated to reflux for two hours and then allowed to stand at room temperature for 16 hours. The reaction mixture was filtered to remove the precipitated sodium bromide. The filtrate was heated to distill off the ethyl alcohol. The residue was recrystallized twice from methyl alcohol, giving 8 parts of 1-phenyl-3-n-octylglycocyamidine, a colorless crystalline material melting at 3688 C.
Example 7 A mixture of 14 parts of sodium phenylcyanamide, 17 parts of a-chloroacetanilide and 300 parts of acetone was warmed on a steam bath for one hour, then allowed to stand at room temperature for 48 hours. The acetone was distilled off, and the residue was washed with water and dried at 65 C. 22 parts (87% yield) of 1,3-diphenylglycocyamidine were obtained. After recrystallization from acetone, the product was a colorless crystalline material melting at 164-l65 C.
Example 8 A mixture of 14 parts of sodium phenylcyanamide, 21.5 parts of a-chloro-p-nitroacetanilide and 150 parts of ethyl alcohol was heated to reflux for three hours and then allowed to stand at room temperature for 16 hours. The reaction mixture was filtered. The filter cake was washed with water and then dried, giving 23 parts (78% yield) of 1-pheny1-3-p-nitropheny1glycocyamidine. After recrystallization from acetone, the product was a yellow, crystallin material melting at 271-273 C.
Example 9 8.73 parts of sodium-p-chlorophenylcyanamide and 4.68 parts of chloroacetamide were dissolved in parts of water and allowed to stand at room temperature for 48 hours. The resulting precipitate was filtered, washed with water and dried at C. 7 parts (67% yield) of l-p-chlorophenylglycocyamidine were obtained. After recrystallization from acetone, the product was a tan-colored, crystalline material melting at 275-278 C. with decomposition.
The glycocyamidines, prepared by the methods of the present invention, are adapted for various uses, more particularly as chemotherapeutic agents, bactericides, and catalysts for the polymerization of unsaturated organic compounds to form high molecular weight linear polymers.
While the invention has been described with particular reference to specific embodiments, it is to be understood that it is not to be limited thereto but is to be construed broadly and restricted solely by the scope of the appended claims.
I claim:
1. A method of preparing a glycocyamidine of the general formula wherein R represents a member of the group consisting of alkyl and aryl radicals, and R represents a member of the group consisting of hydrogen, alkyl and aryl radicals, which comprises reacting an alkali-forming metal salt of a monosubstituted cyanamide of the formula RN M a in which M is an alkali-forming metal, a is an integer not greater than 2 and R is a member of the group consisting of alkyl and aryl radicals, with a haloacetamide of the formula X-CH C=O r sen in which X is a halogen and R is a member of the group consisting of hydrogen, alkyl and aryl radicals, in the presence of a solvent, and recovering the glycocyamidine.
2. The method of claim 1 in which the reaction is .carried out at a temperature within the range of from about 20-150 C.
3. A method of preparing l-phenylglycocyami- .dine which comprises reacting sodium phenylcyanamide withv chloroacetamide in the presence of a solvent, and recovering the 1-phenylglycocyamidine.
4. A method of preparing l-n-octylglycocyamidine which comprises reacting sodium n-octylcyanamide with chloroacetamide in the presence of a solvent, and recovering the l-n-octylglycocyamidine.
5. A method of preparing 1-phenyl-3-n-octylglycocyamidine which comprises reacting sodium phenylcyanamide with a-bromo-N-n-octylacetamide in the presence of a solvent, and recovering the 1-phenyl-3n-octylglycocyamidine.
ERICK I. HOEGBERG.
No references cited.
7 Patent No. 2,557 ,911
Certificate of Correction June 19, 1951 ERICK I. HOEGBERG It is hereby certified that error appears in the printed specification of the above numbered patent requiring correction as follows:
Column 2, line 17, for presses read process;
and that the said Letters Patent should be read as corrected above, so that the same may conform to the record of the case in the Patent Oflice.
Signed and sealed this 28th day of August, A. D. 1951.
THOMAS F. MURPHY,
Assistant (Jommiasz'oner of Patents.

Claims (1)

1. A METHOD OF PREPARING A GLYCOCYAMIDINE OF THE GENERAL FORMULA
US156933A 1950-04-19 1950-04-19 Method of preparing glycocyamidines Expired - Lifetime US2557911A (en)

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2161917A1 (en) * 1971-10-21 1973-07-13 American Cyanamid Co
US4044021A (en) * 1971-10-21 1977-08-23 American Cyanamid Company Tetrasubstituted imidazolidine diuretics useful in the treatment of hyperaldosteronism
US4110445A (en) * 1972-10-02 1978-08-29 American Cyanamid Company Method for antagonizing aldosteronic action and inducing diuresis by administering a tetrasubstituted imidazolidine
FR2423485A1 (en) * 1978-04-21 1979-11-16 Egyt Gyogyszervegyeszeti Gyar NEW SUBSTITUTED 1,3-DIARYL-2-IMINO-IMIDAZOLIDINES AND 1,3-DIARYL-2-IMINO-HEXAHYDRO-PYRIMIDINES, METHODS FOR THE PREPARATION OF THESE COMPOUNDS AND MEDICINAL PRODUCTS CONTAINING THEM

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
None *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2161917A1 (en) * 1971-10-21 1973-07-13 American Cyanamid Co
US4044021A (en) * 1971-10-21 1977-08-23 American Cyanamid Company Tetrasubstituted imidazolidine diuretics useful in the treatment of hyperaldosteronism
US4110445A (en) * 1972-10-02 1978-08-29 American Cyanamid Company Method for antagonizing aldosteronic action and inducing diuresis by administering a tetrasubstituted imidazolidine
FR2423485A1 (en) * 1978-04-21 1979-11-16 Egyt Gyogyszervegyeszeti Gyar NEW SUBSTITUTED 1,3-DIARYL-2-IMINO-IMIDAZOLIDINES AND 1,3-DIARYL-2-IMINO-HEXAHYDRO-PYRIMIDINES, METHODS FOR THE PREPARATION OF THESE COMPOUNDS AND MEDICINAL PRODUCTS CONTAINING THEM

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