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Патент USA US3055887

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35,655,882
Patented Sept. 25, 1962
ll
2
formed with organic acids, particularly with carboxylic'
3,055,882
acids, such as lower aliphatic carboxylic acids, for ex;
REDUCTIUN PRUCESS FUR PREPARATION OF
CYCLE? NETRQGEN COMPOUNDS
ample, lower alkanoic acids, e.g. acetic, propionic or?
pivalic acid and the like,’ substituted‘ lower alkanoic
Robert Paul Mull, Florham Park, N.J., assignor to Cilia
acids, e.g. trichloroacetic, hydroxyacetic or cyclopentyl~*
propionic acid and the like, or lower alkenoic acids, e.g'.
acrylic acid and the like, with aromatic carboxylic acids;
for example, monocyclic aromatic carboxylic acids, e.g.~
The present invention concerns a process for the
benzoic, hydroxybenzoic or aminobenzoic‘ acid; and the"
preparation of guanidino compounds. More particu 10 like, or bicyclic aromatic carboxylic acids, e.g. l-naphe
larly, the procedure of the invention relates to the man
thoic or Z-naphthoic acid and the like, with carbocyclic‘
(Torporation, a corporation of Delaware
No Drawing. Filed June llll, 1959, Ser. No. 819,209
11 Claims. (Cl. Mil-239)
ufacture of (N,N-alkylene-imino)-lower alkyl-guani
aryl-lower aliphatic acids, such as monocyclic carbocyclic
dines, in which alkylene contains from four to ten car
aryl-lower alkanoic acids, e.g. phenylacetic acid or [3
bon atoms as ring members, and the salts thereof. Also
phenylpropionic acid and the like, or with heterocyclic
anticipated are quaternary ammonium compounds and 15 carboxylic acids, for example, monocyclic heterocyclic
acyl derivatives of these compounds, whenever prepared
carboxylic acids, e.g. nicotinic, isonicotinic or 2-furoic
according to the procedure of the invention.
acid and the like.
N,N-alkylene-imino radicals, containing from four to
The above-mentioned derivatives and salts thereof have
ten carbon atoms, primarily from six to eight carbon
antihypertensive properties and can be used as antihyper
atoms, are unsubstituted, or may contain as further sub
tensive agents to relieve hypertensive conditions, par
stituents of carbon atoms lower hydrocarbon radicals,
such as lower alkyl, e.g. methyl or ethyl. They may be
ticularly neurogenic or renal hypertension. A particular
characteristic of this antihypertensive effect is its long
represented by N,N-tetramethylene~imino (l-pyrrolidino),
duration, which property is especially desirable in the
N,N-pentamethylene-imino (l-piperidino), N,N-hexa
treatment of chronic hypertensive states. Particularly
methylene-imino (l-hexahydro-azepino), N,N-hepta 25 valuable with respect to their long-lasting antihyperten
methylene-imino (l-octahydroazocino), N,N-octamethyl
sive activity are the (N,N-alkylene-imino)-lower alkyl
ene-imino (l~octahydro - azonino), N,N-nonamethylene
guanidines, in which the N,N-alkyleneimino iportion con
imino (l-decahydro-azecino) or N,N-decamethylene
tains from six to eight, primarily seven, carbon atoms,
imino radicals.
_
and carries no additional substituents or only methyl
The lower alkyl radical, linking the alkylene-imino
groups, and in which lower alkyl, containing from two
to three carbon atoms, separates the N,N-alkylene-imino
portion from the guanidino group by two to three car
bon atoms, and their salts with inorganic acids, such as
mineral acids, e.g. hydrochloric or sulfuric acid, or with
ring with the guanidino group, contains from two to
seven carbon atoms and is represented by a lower alkyl
ene radical, which may also be branched. Such alkyl
ene radicals contain preferably from two to three carbon
atoms and are represented, for example, by 1,2-ethylene,
1-methyl-l,2 ethylene, 2-methyl-l,2-ethylene or 1,3-propyl
organic acids, such as hydroxy-substituted aliphatic acids,
e.g. tartaric or citric acid, or unsaturated aliphatic acids,
e.g. maleic acid. This group is represented by the (N,N
ene; additional alkylene radicals are, for example, 2,3
butylene, 1,3-butylene, 1,4-butylene, 1,4-pentylene, 1,5
heptamethylene-imino)-lower alkyl guanidines, particu
pentylene and the like.
larly the guanidine compound of the formula:
The guanidino group is preferably unsubstituted. 40
However, the amino, as well as the irnino groups of the
guanidino portion may be substituted by lower hydro
carbon radicals, such as lower alkyl, e.g. methyl or ethyl.
Such substituted guanidino groups are, for example, N
U
NH2
monomethyl-, N-polymethyl-, N-monoethyl— or N~poly 45
ethyl-guanidino groups.
and their therapeutically useful inorganic acid addition
Salts of the compounds prepared according to the
salts, particularly their sulfates.
The process of this invention comprises converting in
process of this invention are particularly therapeutically
(N,N-alkylene-imino)-lower alkyl carboxylic acid gua
useful acid addition salts, such as ‘those with inorganic
acids, for example, hydrohalic acids, e.g. hydrochloric 50 nides or guanidino-lower alkyl carboxylic acid N,N-lower
alkylene-imides, the carbonyl group of the amide por
tion to a methylene group, and, if desired, converting a
or hydrobromic acid, sulfuric or phosphoric acids, or
those with organic acids, such as formic, acetic, propi_
onic, glycolic, lactic, pyruvic, oxalic, malonic, succinic,
maleic, fumaric, malic, tartaric, citric, ascorbic, hydroxy
maleic, dihydroxymaleic, benzoic, phenylacetic, 4-amino
resulting salt into the free compound, and/or, if de
sired, converting the free compound into a salt, an acyl
55 or a quaternary ammonium derivative thereof.
The reduction of the carbonyl portion of the amide‘
benzoic, 4-hydroxybenzoic, anthranilic, cinnamic, man
delic, salicylic, 4- aminosalicylic, Z-phenoxybenzoic, 2
acetoxy-benzoic, methane sulfonic, ethane sulfonic, hy
groups may be carried out by treatment with an aluminum
hydride, particularly an alkali metal aluminum hydride,
e.g. lithium aluminum hydride or sodium aluminum hy
droxyethane sulfonic acid and the like.
The guanidine compounds may also form quaternary 60 dride, or an earth alkaline metal aluminum hydride, e.g.
magnesium aluminum hydride, or aluminum hydride.
ammonium compounds, particularly those with lower
The reduction with these reagents is preferably performed
alkyl halides, e.gl methyl, ethyl, propyl or isopropyl chlo
in the presence of a solvent, particularly an ether, such
ride, bromide or iodide, or lower alkyl lower alkane
as a di-lower alkyl ether, e.g. diethyl ether, a lower alkyl
sulfonates, e.g. methyl or ethyl methane or ethane sul
fonate, as well as the corresponding quaternary am
monium hydroxides and the salts which may be formed
from the quaternary ammonium hydroxides by the reac
65
carbocyclic aryl ether, e.g. anisole, a di-carbocyclic aryl
ether, e.g. diphenyl ether, or a cyclic ether, e.g. tetra
hydrofurane or p-dioxane, and, if desired, at an elevated
tion with inorganic acids other than hydrohalic acids
temperature and/or in the atmosphere of an inert gas,
e.g. nitrogen.
or with orgahic acids, such as those outlined above for
the preparation of the acid addition salts.
The desired conversion may also be carried out by
70
Acyl derivatives of the guanidine compounds prepared
electrolytically reducing the amide derivatives on a cath
according to the procedure of this invention are those
ode of a high overpotential such as a cadmium, zinc,
3,055,882
4
alkylene-imine with a cyano-lower alkyl-halide, e.g. chlo
ride, and reducing in a resulting (2-oxo-l-l\I,N-alkylene
mercury, lead amalgam or lead. The catholyte used in
such a reduction is preferably a mixture of water, sul
imino)-lower alkyl nitrile the nitrile group to a methyl
eneamino group, which may be accomplished, for ex
ample, by treatment with a hydride, such as an aluminum
furic acid and a lower alkanoic acid, e.g. acetic or pro
pionic acid. A platinum, carbon, lead or stainless steel
anode may be used; the anolyte is preferably sulfuric acid.
The starting materials used in the above reduction pro
cedure may be prepared, for example, by treating a re
hydride, e.g. lithium aluminum hydride. The 2-0240-1
N,N-alkylene-imine may also be reacted with a lower
alkene-nitrile, e.g. acrylonitrile, to yield the (2-oxo-1-N,N
alkylene-imino)-lower alkyl nitrile, which is then re
active functional derivative of an (N,N-alkylene-imino)
lower alkyl carboxylic acid or of a guanidino-lower alkyl
duced to the desired amino compound as shown herein
carboxylic acid with a guanidino or an N,N-alkylene
above. The thus obtained (2-ox0-1-N,N-alkylene-imi
imine, respectively, to form the desired amide com
pounds. Reactive derivatives of carboxylic acids are,
for example, esters, such as lower alkyl, e.g. methyl or
ethyl, esters of activated esters, which are particularly
no)-lower alkyl-amine may then be converted to the cor
responding guanidine, for example, by treatment with
a salt of an S-lower alkyl-isothiourea, such as the S
methyl-isothiourea sulfate.
useful for the formation of amide bonds, such as esters
A resulting (2-oxo-1-N,N-alkylene-imino)-lower alkyl
with reactive mercaptan compounds, e.g. mercapto-acetic
guanidine compound may be converted to the (Z-thiono
l-N,N-alkylene-imino)-lower alkyl-guanidine, for exam
ple, by treatment with phosphorus trisul?de or phosphorus
ing to procedures which are known for the manufacture
of analogous esters. Other reactive functional deriva~ 20 pentasul?de as shown hereinbefore.
acid, or with reactive hydroxyl compounds, e.g. hy
droxy-acetonitrile. Such esters may be prepared accord
tives of acids are the acid addition salts of acid halides,
particularly the hydrochloride of an acid chloride, which
maybe prepared according to standard methods.
The reaction of these reactive functional derivatives
of carboxylic acids with the amino compounds may be 25
carried out, for example, by treating a salt of an acid
The above-described starting materials are new and are
intended to be included within the scope of this inven
tion. Such compounds are, for example, (N,N-alkylene
imino)-lowcr alkyl carboxylic acid guanides, in which
alkylene has the above-given meaning, and salts thereof.
A preferred group of compounds are (N,N~alkylene
imino)-lower alkyl carboxylic acid guanides, in which
halide, particularly the hydrochloride of an acid chloride
with the amine, preferably in a polar, but non-hydrox
ylated solvent, such as, for example, dimethylformamide,
alkylene contains from six to eight carbon atoms, the
lower alkyl carboxylic acid portion contains from two to
three carbon atoms, separating the N,N-alkylene-imino
diethyleneglycol dimethylether, dioxane, tetrahydrofuran
portion from the guanidino group by two to three car
and the like.
A modi?cation of the above procedure comprises the
bon atoms, and the guanidino group ,is otherwise unsub
stituted. This preferred group may be represented by
converting in (N,N-alkylene-imino)-lower alkyl thiocar
the (l-N,N-heptamethylene-imino)-acetic acid guanide.
boxylic acid guanides or guanidino-lower alkyl thiocar
boxylic acid N,N-alkylene-imides, the thiocarbonyl group 35 These amide compounds may also be prepared by treating
a reactive ester, formed by a hydroxy-lower alkyl car
of the thioarnide portion into a methylene group, and, if
boxylic acid guanide with a strong acid, for example, a
desired, carrying out the optional steps.
hydrohalic acid, e.g. hydrochloric acid, with the N,N
The replacement of the sulfur in the above-mentioned
thioamides may be carried out by desulfurization, for
example, with a freshly prepared hydrogenation catalyst,
alkylene-imine, if desired, in the form of a salt, such as
Such reactive esters are,
40 an alkali metal salt thereof.
for example, chloro-lower alkyl carboxylic acid guanides.
such as Raney nickel, in an alcoholic solvent, e.g. meth
Another group of valuable intermediates are the (N,N
anol or ethanol, if desired, in the presence of hydrogen,
alkylene-imino)-lower alkyl thiocarboxylic acid guanides,
or electrolytically according to the procedure outlined
in which alkylene has the above-given meaning, and salts
hereinabove for the reduction of the amides.
The thioamides used as the starting materials in this 45 thereof. These compounds are represented by the group
modi?cation may be prepared from the corresponding
amides previously mentioned, for example, by treatment
with phosphorus trisul?de or phosphorus pentasul?de.
A modi?cation may consist in electrolytically reducing
of (N,N-alkylene-imino)-lower alkyl thiocarboxylic acid
guanides, in which alkylene contains from six to eight
carbon atoms, the lower alkyl thiocarboxylic acid portion
contains from two to three carbon atoms, and separates
the amide in the presence of an alkali metal sul?de, e.g. 50 the N,N-alkylene-imino portion ‘from the guanidino
group by two to three carbon atoms, and the guanidino
sodium sul?de, thereby forming the thioamide as a non
group is otherwise unsubstituted; the (1-N,N-heptameth
isolated intermediate.
ylene-imino)-thioacetic acid guanide illustrates this pre
Another method to prepare the above described guani
ferred group.
dino compounds comprises replacing in (2-R-l-N,N
alkylene-imino)-lower alkyl-guanidines, in which R rep 55
resents an oxo group of the formula =0 or a thiono group
of the formula :8, such group by two hydrogen atoms,
and, if desired, carrying out the optional steps.
The above-mentioned oxo and thiono groups form to
Also included are the guanidino-lower alkyl carboxylic
acid N,N-alkylene-imides, in which alkylene has the
above-given meaning, and salts thereof. This series of
intermediates is represented by the preferred group of
guanidino-lower alkyl carboxylic acid N,N-alkylene
gether with the nitrogen atom of the N,N-alkylene-imino 60 imides, in which alkylene contains from six to eight car
bon atoms, the lower alkyl carboxylic acid portion con
portion an amide or a thioamide group. Such groups
tains from two to three carbon atoms, separating the N,N
may be converted into the desired methyleneimino group
alkylene-imino portion from the guanidino group by the
by the previously described procedures; for example, an
same number of carbon atoms, and the guanidino group
oxo group of an amide grouping may be replaced by
two hydrogen atoms by treatment with an aluminum 65 is otherwise unsubstituted. The guanidino-acetic acid
hydride, such as lithium aluminum hydride, or a thiono
group of a thioamide grouping may be exchanged for
two hydrogen atoms by desulfurization with a freshly
prepared hydrogenation catalyst, such as Raney nickel.
These reactions are carried out as previously shown.
The starting material used in this modi?cation may be
prepared, for example, by introducing into a 2-oxo-1
N,N-alkylene-imine an amino-lower alkyl radical, which
may be accomplished, for example, by reacting an alkali
metal, e.g. lithium or sodium, salt of the 2~oxo-1-N,N 75
N,N-heptamethylene-imide represents this preferred
group of compounds. These compounds may also be
prepared, ‘for example, by treating a guanidine with a
reactive ester, formed by a hydroxy-lower alkyl car
boxylic acid N-N-alkylene-imide and a strong acid, such
as a mineral acid, e.g. hydrochloric acid.
Such reac
tive esters are, for example, chloro-lower alkyl carboxylic
acid N,N-lower alkylene-imides.
Furthermore, the above-disclosed guanidino-lower al
kyl thiocarboxylic acid N,N-alkylene-imides, in which
3,055,882‘
5
alkylene has the previously given meaning, and their salts
are also part of the present invention.
The reaction is preferably carried out in an inert solvent,
for example, in a hydrocarbon, such as an aliphatic hy
They are rep
resented by the preferred group of guanidino-lower alkyl
drocarbon, e.g. hexane, or an aromatic hydrocarbon,
thiocarboxylic acid N,N-alkylene-imides, in which alkyl
e.g. benzene, toluene or xylene, or in a tertiary organic
base, such as a liquid pyridine compound, e.g. pyridine
ene contains from six to eight carbon atoms, the lower
alkyl thiocarboxylic acid portion contains ‘from two to
or collidine.
three ‘carbon atoms, separating the N,N-alkylene-imino
portion from the guanidino group by two to three carbon
The guanidine compounds may be converted into the
quaternary ammonium compounds by reacting the ter
atoms, and the guanidino group is otherwise unsubsti
tiary bases with an ester formed by a hydroxylated lower
tuted, and illustrated, for example, by the guanidino-thio 10 hydrocarbon compound with a strong inorganic or or—
acetic acid l-N,N-heptarnethylene-imide.
ganic acid. Hydroxylated lower hydrocarbon compounds
The (2-oxo-1-N,N-alkylene-imino)-lower alkyl-guani
contain from one to seven carbon atoms and the esters
dines, in which ‘alkylene has the previously given mean
thereof are more especially those with mineral acids, e.g.
ing, as well as their salts, represent a further group of
valuable intermediates, which may be illustrated by the
preferred group of (2-oxo-1-N,N~alkylene-imino)-lower
alkyl-guanidines, in which alkylene contains from six to
eight carbon atoms, lower alkyl contains from two to
three carbon atoms separating the guanidino group from
the alkylene-imino portion by two to three carbon atoms,
and the guanidino group is otherwise unsubstituted. The
hydrochloric, hydrobromic, hydriodic, or sulfuric acid.
Such esters are speci?cally lower alkyl halides, e.g.
methyl, ethyl or propyl chloride, bromide or iodide, or
lower alkyl lower alkane sulfonates, e.g. methyl or ethyl
methane or ethane sulfonate. The quaternizing reaction
may be performed in the presence or absence of a sol
20 vent; suitable solvents are more especially lower alkanols,
e.g. methanol, ethanol, propanol, isopropanol, tertiary
2 - (2~oxo-1-'N,N-heptamethylene-imino)-ethyl-guanidine
butanol or pent-anol, lower alkanones, e.g. acetone or
represents one of the preferred members.
Also included are the (2-thiono-1-N,N-alkylene
ethyl methyl ketone, or organic acid amides, e.g. form
amide or dimethylformamide. If necessary, an elevated
temperature and/ or a closed vessel may be employed.
imino)-lower alkyl guanidines, in which alkylene has the
previously given meaning, and the salts thereof. A pre
ferred group of these intermediates are the (Z-t-hiono-l
The invention also comprises any modi?cation of the
general process wherein a compound obtainable as an
intermediate at any stage of the process is used as start
TN,N-alkylene-imino)-lower alkyl-guanidines, in which al
lkylene contains from six to eight carbon atoms and lower
:alkyl from two to three carbon atoms separating the
guanidino group‘ from the alkylene-imino portion by two
to three carbon atoms, whereas the guanidino group is
otherwise unsubstituted. This group may be represented
by the 2-(2-thiono-1-N,N-heptamethylene-imino)-ethyl
.guanidine.
A combination of the two principal modi?cations of
the process of the present invention may also be antic
ipated. For example, upon treatment of a (Z-oxo-l
ing material and the remaining steps(s) of the process
is (are) carried out, as well as any new intermediates.
‘In the process of this invention such starting materials
are preferably used which lead to ?nal products men
tioned in the beginning as preferred embodiments of the
invention.
35
As used herein, the term “thiocarboxylic acid” (or
derivative thereof) refers to a structure in which the
sulfur is a thiono sulfur, i.e, double bonded to carbon.
The following examples illustrate the invention and are
ZN,N-alkylene-imino')-lower alkyl carboxylic acid guanide
not to be construed as being limitations thereon. Tem
or of a guanidino-lower alkyl-carboxylic acid 2-oxo-1 40 peratures are given in degrees centigrade.
N,N-alkylene-imide, in which alkylene has the above
given meaning, with one of the reduction reagents pre
viously described, the desired (N,N-alkylene-imino)
lower alkyl~guanidines described hereinbefore, may be
Example 1
13.6 g. of chloroa-cetyl guanide is added while stirring
to a solution of ‘22.6 g. of heptamethylene-imine in 200
formed. The starting materials used in such a procedure 45 ml. of benzene. After warming for one hour, and then
may be prepared along the previously outline procedures
cooling, the solution is ?ltered and the ?ltrate concen
by selecting the appropriate intermediates.
trated under reduced pressure.
Likewise, (2-thiono-l-N,N-alkylene-imino)-lower alkyl
The residue, containing the 2-('1-N,N-heptamethylene
thiocarboxylic acid guanides or guanidino-lower alkyl
imino)~acetic acid guanide, is suspended in tetrahydro
thiocarboxylic acid 2-thiono-1-N,=N-alkylene-imides may 50 furane and added to a re?uxing solution ‘of 6 g. of lithium
be converted to the desired (N,N-alkylene-imino)-lower
aluminum hydride in tetrahydrofuran. After comple
alkyl-guanidines, for example, by desulfurization as out
tion of the reaction, the excess of lithium aluminum
lined hereinabove. The above starting materials may be
hydride is decomposed by adding water, then aqueous
prepared according to the previously outline procedures
sodium hydroxide. The solid material is ?ltered off, the
by selecting the appropriate intermediates.
55 ?ltrate is acidi?ed with sulfuric acid and the 2-(1-N,N
Depending on the conditions used, the guanidine com
pounds are obtained in the form of the free compounds
or as the Salts thereof. ~A salt may be converted into the
free compound in the customary way, for example, by
treatment with an alkaline reagent, such as an aqueous 60
alkali metal hydroxide, e.g. lithium, sodium or potas
sium hydroxide, an aqueous alkali metal carbonate, e.g.
lithium, sodium or potassium carbonate or hydrogen
heptarnethylene-imino)-ethyl-guanidine sulfate can be re
covered and recrystallized from aqueous ethanol, M.P.
276-281 ° (with decomposition) .
Example 2
16.6 g. of 3a(2-oxo-1-N,N-hexamethylene-imino)
propionitrile is dissolved in absolute ethanol and hydro
genated over 2 g. of Raney nickel ‘at a temperature of
about 125° and under pressure. After the necessary
transformed into its therapeutically useful acid addition 65 amount of hydrogen is taken up, the solution is cooled
carbonate, or aqueous ammonia.
A free base may be
salts by reaction with an appropriate inorganic or organic
acid, such as one of those outlined hereinabove, pref
erably in the presence of a solvent, such as a lower al
‘and the catalyst removed by ?ltration. The ?ltrate is
treated with 13.9 g. of S-methyl-isothiourea sulfate; the
mixture is re?uxed until the evolution of methyl-mercap
kanol, e.g. methanol, ethanol, propanol or isopropanol,
tan ceases. The solution is concentrated under reduced
or an ether, e.g. diethylether or p-dioxane, and the like. 70 pressure, the residue is taken into water, aqueous sodium
Acyl derivatives of the guanidine compounds of the
present invention may be prepared, for example, by treat—
ing a resulting guanidine compound with the reactive
derivative of a carboxylic acid, for example, with \a halide,
hydroxide is added, and the aqueous layer is extracted
with ether.
The ether solution is dried and then added to a solution
of 5 g. of lithium aluminum hydride in 500 ml. of ether.
e.g. chloride, or with the anhydride of a carboxylic acid. 75 The reaction mixture is re?uxed overnight, the excess of
3,055,882
7
3
and the lower alkyl thiocarboxylic acid portion has from
lithium aluminum hydride is decomposed by adding water
two to three carbon atoms and separates the N,N-alkyl
ene-imino portion from the guanidino group by two to
and the reaction mixture is ?ltered. The solvent is evap
orated, and the residue, containing the 3-(N,N-hexameth
ylene-imino)-propyl-guanidine, is converted to the sul
fate by adding dilute sulfuric acid and concentrating the
three carbon atoms, and acid-addition salts thereof.
5. (1-N,N-heptamethylene-imino)-acetic acid guanide.
6. (1~N,N-heptamethylene-imino)thioacetic acid gua
aqueous solution.
nide.
The starting material may be prepared by slowlyv add
7. Guanidino acetic acid N,N-heptamethylene-imide.
ing to a solution of 56.5 g. of caprolactam in 150 ml.
8. Guam'dino - thioacetic acid N,N - heptamethylene
of p-dioxane, 28 g. of acrylonitrile while stirring and
cooling. A few drops of a strong base, such as benzyl
trimethylammonium hydroxide, are added to initiate the
reaction, and the temperature is maintained between 30
35° for one-half hour. The mixture is allowed to stand
for several days at room temperature, and is then acidi?ed
imide.
9. A member selected from the group consisting of
imino)-propionitrile by distillation, B.P. l33-l36°/ 0.3
the 2-R-l-N,N-alkylene-imino portion from the guanidino
(2-R-1—N,N-alkylene~imino)-lower alkyl-guanidine, in
which alkylene has six to eight carbon atoms, R is a
member selected from the group consisting of 0x0 of the
with hydrochloric acid. The residue, after evaporating 15 formula =0 and thiono of the formula :8, and lower
alkyl has from two to three carbon atoms and separates
the solvent, yields the desired 3-(l-N,N-hexamethylene
group by two to three carbon atoms, and addition salts
thereof.
What is claimed is:
10. 2 - (2 - oxo - 1 - N,N - heptamethylene - imino)
1. A member selected from the group consisting of 20
mm.
ethyl-guanidine.
(N,N-alkylene-imino)-lower alkyl carboxylic acid gua
11. 2 - (2 - thiono - 1 - N,N - heptamethylene - imino)
nide, in which alkylene has six to eight carbon atoms,
and the lower alkyl carboxylic acid portion has from two
to three carbon atoms and separates the N,N-alkylene
imino portion from the guanidino group by two to three
carbon atoms, and acid addition salts thereof
2. A member selected from the group consisting of
ethyl-guanidine.
References Cited in the ?le of this patent
UNITED STATES PATENTS
2,846,382
2,852,510
2,852,528
2,909,523
2,957,867
(N,N-alkylene-imino)-lower alkyl thiocarboxylic acid
guanide, in which alkylene has six to eight carbon atoms,
and the lower alkyl thiocarboxylic acid portion has from
two to three carbon atoms and separates the N,N-alkyl
ene-imino portion from the guanidino group by two to
three carbon atoms, and acid-addition salts thereof.
guanidino-lower alkyl carboxylic acid N,N-alkylene
1958
1958
1958
1959
1960
FOREIGN PATENTS
3. A member selected from the group consisting of
imide, in which alkylene has six to eight carbon atoms,
and the lower alkyl carboxylic acid portion has from
Allen _________________ __ Aug. 5,
Hoffmann et al ________ __ Sept. 16,
Ho?mann et al ________ .. Sept. 16,
Bach et al. ___________ __ Oct. 20,
Werner _____________ __ Oct. 25,
35
874,447
Germany ____________ __ Apr. 23, 1953
OTHER REFERENCES
Cook et al.: J. 'Phys. Chem., vol. 36, pp. 2383-89
two to three carbon atoms and separates the N,N-alkyl
ene-imino portion from the guanidino group by two to
(1932).
Sidgwick: Organic Chemistary of Nitrogen (1937),
40
three carbon atoms, and acid-addition salts thereof.
pp. 297-298.
4. A member selected from the group consisting of
guanidino-lower alkyl thiocarboxylic acid N,N-alkylene
imide, in which alkylene has six to eight carbon atoms,
Migrdichian: Organic Synthesis, v01. 1, pp. 176-186
(1957).
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