DERIVES N-ACYL DE LA SYDNONIMINE ET METHODE DE PREPARATION

SYDNONIMINE N-ACYLDERIVATIVES AND METHOD FOR PREPARING SAME

Abrégé anglais

Abstract
Novel sydnonimine N-acyl derivatives of the formula
(I):
<IMG> (I)
wherein
R is selected from the group consisting of phenyl,
.beta.-phenylethyl, d,1-.alpha.-methyl-.beta.-phenylethyl and 1-.alpha.-methyl-.beta.-
phenylethyl:
R' is selected from the group consisting of hydrogen
and phenyl;
X is selected from the group consisting of a lower
alkyl, phenyl and a group of formula
<IMG>
wherein R" is selected from the group consisting of hydrogen,
halogen and lower fluorinated alkyl; R"' is selected from the
group consisting of hydrogen, halogen and lower alkyl; with
the proviso that when X is said group of formula
<IMG>
and R', R" and R"' are hydrogen, R is 1-.alpha.-methyl-.beta.-phenylethyl;
the compounds possess a psychostimulant activity at a low
toxicity and can be used as the active ingredient of medicine.

Revendications

The embodiments of the invention in which an exclusive property
or privilege is claimed are defined as follows:
1. A method for preparing an N-acyl derivative of sydnon-
imine of the formula (I):
<IMG> (I)
wherein
R is selected from the group consisting of phenyl,
.beta.-phenylethyl, d,1-.alpha.-methyl-.beta.-phenylethyl and 1-.alpha.-methyl-.beta.-
phenylethyl;
R' is selected from the group consisting of hydrogen
and phenyl;
X is selected from the group consisting of a lower
alkyl, phenyl and a group of formula
<IMG>
wherein R" is selected from the group consisting of hydrogen,
halogen and lower fluorinated alkyl; R"' is selected from the
group consisting of hydrogen, halogen and lower alkyl, with
the proviso that when X is said group of formula
<IMG>
and R', R" and R"' are hydrogen, R is 1-.alpha.-methyl-.beta.-phenylethyl.
comprising reacting an N-nitroso derivative of an N-substituted
nitrile of an .alpha.-aminoacid of the formula (II):
17

<IMG> (II)
wherein R and R' are as defined above, with an acylation
agent selected from the group consisting of haloanhydrides
of carboxylic acids, anhydrides of carboxylic acids and
arylisocyanates, in an organic solvent medium in the presence
of a basic catalyst followed by isolation of the product of
formula (I).
2. A method as claimed in claim 1, wherein the organic
solvent is selected from the group consisting of benzene,
toluene and dichloroethane.
3. A method as claimed in claim 1, wherein the catalyst
is selected from the group consisting of triethylamine,
dimethylbenzylamine and N-methylmorpholine.
4. A method as claimed in claim 1, wherein the process
is carried out at a temperature within the range of 40 to
60°C.
5. A method as claimed in claim 1, wherein R is selected
from the group consisting of .beta.-phenylethyl, d,1-.alpha.-methyl-.beta.-
phenylethyl and 1-.alpha.-methyl-.beta.-phenylethyl; R' is hydrogen or
phenyl, and X is selected from the group consisting of methyl
and
<IMG>
18

wherein R" is hydrogen, halogen or fluorinated methyl and R"'
is hydrogen, halogen or methyl.
6. A method according to claim 1, wherein, in said
derivative (II), R is .beta.-phenylethyl and R' is hydrogen, and
said acylating agent is p-chlorophenylisocyanate.
7. A method according to claim 1, wherein, in said
derivative (II), R is .alpha.-methyl-.beta.-phenylethyl and R' is
hydrogen, and said acylating agent is p-chlorophenylisocyanate.
8. A method according to claim 1 for preparing N-p-
chlorophenylcarbamoyl-3-(.beta.-phenylethyl)-sydnonimine comprising
reacting N-nitroso-N-(.beta.-phenylethyl)-aminoacetonitrile with
p-chlorophenylisocyanate.
9. A method according to claim 1 for preparing d,1-N-p-
chlorophenylcarbamoyl-3-(.alpha.-methyl-.beta.-phenylethyl)-sydnonimine
comprising reacting d,1-N-nitroso-(.alpha.-methyl-.beta.-phenylethyl)-
aminoacetonitrile with p-chlorophenylisocyanate.
10. A method according to claim 9, wherein the catalyst
is trimethylamine.
11. A method according to claim 9, wherein the catalyst
is dimethylbenzylamine.
12. A method according to claim 9, wherein the catalyst
is N-methylmorpholine.
13. A method according to claim 1 for preparing 1-N-
phenylcarbamoyl-3-(.alpha.-methyl-.beta.-phenylethyl)-sydnonimine
comprising reacting 1-N-nitroso-N-(.alpha.-methyl-.beta.-phenylethyl)-
aminoacetonitrile with phenylisocyanate.
19

14. A method according to claim 1 for preparing 1-N-
p-chlorophenylcarbamoyl-3-(.alpha.-methyl-.beta.-phenylethyl)-sydnonimine
comprising reacting 1-N-nitroso-N-(.alpha.-methyl-.beta.-phenylethyl)-
aminoacetonitrile with p-chlorophenylisocyanate.
15. An N-acyl derivative of sydnonimine of formula (I),
as defined in claim 1, whenever prepared by the method of
claim 1, 2 or 3 or by an obvious chemical equivalent.
16. An N-acyl derivative of sydnonimine of formula (I),
as defined in claim 1, whenever prepared by the method of
claim 4 or by an ohvious chemical equivalent.
17. An N-acyl derivative of sydnonimine of formula (I),
as defined in claim 1, wherein R is selected from the group
consisting of .beta.-phenylethyl, d,1-.alpha.-methyl-.beta.-phenylethyl and
1-.alpha.-methyl-.beta.-phenylethyl; R1 is hydrogen or phenyl; and X
is selected from the group consisting of methyl and
<IMG>
wherein R" is hydrogen, halogen or fluorinated methyl and R"'
is hydrogen, halogen or methyl, whenever prepared by the
method of claim 5 or by an obvious chemical equivalent.
18. An N-acyl derivative of sydnonimine of formula (I),
as defined in claim 1, wherein R is .beta.-phenylethyl, R' is
hydrogen and X is p-chlorophenylamino, whenever prepared
by the method of claim 6 or by an obvious chemical equivalent.
19. An N-acyl derivative of sydnonimine of formula (I),
as defined in claim 1, wherein R is .alpha.-methyl-.beta.-phenylethyl,
R' is hydrogen and X is p-chlorophenylamino, whenever prepared

by the method of claim 7 or by an obvious chemical equivalent.
20. N-p-Chlorophenylcarbamoyl-3-(.beta.-phenylethyl)-
sydnonimine, whenever prepared by the method of claim 8
or by an obvious chemical equivalent.
21. d,1-N-p-Chlorophenylcarbamoyl-3-(.alpha.-methyl-.beta.-
phenylethyl)-sydnonimine, whenever prepared by the method
of claim 9, 10 or 11, or by an obvious chemical equivalent.
22. d,1-N-p-Chlorophenylcarbamoyl-3-(.alpha.-methyl-.beta.-
phenylethyl)-sydnonimine, whenever prepared by the method
of claim 12, or by an obvious chemical equivalent.
23. 1-N-Phenylcarbamoyl-3-(.alpha.-methyl-.beta.-phenylethyl)-
sydnonimine, whenever prepared by the method of claim 13
or by an obvious chemical equivalent.
24. 1-N-p-Chlorophenylcarbamoyl-3-(.alpha.-methyl-.beta.-
phenylethyl)-sydnonimine, whenever prepared by the method
of claim 14 or by an obvious chemical equivalent.
21

Description

~7~
The present invention relates to novel sydnonimine
derivatives and a method for preparing them. ~he compounds
possess a pronounced psychostimulant activity and can be
useful as the act.ive principle of a medicated composition.
The sydnonimine N--acyl derivatives according to the
present invention are novel compounds hitherto unknown in the
literature.
In accordance with the present invention, novel
sydnonimine N-acyl derivatives have the formula (I):
R - N - C - R'
N - C = N - C - X (I)
\ / 11
O O
wherein
R is selected from the group consisting of phenyl,
~-phenylethyl, d,l-~-methyl-~-phenylethyl and l-~-methyl-~-
phenylethyl;
R' is selected from the group consisting of hydrogen
and phenyl;
X is select~d from the group consisting of a lower
alkyl, phenyl and a group of formula
R"
wherein R" is selected from the group consisting of hydrogen,
halogen and lower fluorinated alkyl: R"' is selected from the
group consisting of hydrogen~ halogen and lower alkyl; with
the proviso that when X is said group of formula
-NH ~R"
R"
- 2
~B .i
,

R'~ R" and R"' are hydrogen, and R is l-~-methyl-~-phenylethyl.
The compounds are white or white with a yellowish
tint crystalline substances stable in the air, sparingly
soluble in water, soluble in chloroform and less soluble
in alcohol.
In another aspect of the invention there is provided
a method of preparing an N-acyl derivative of sydnonimine of
formula (I), as defined above9 which comprises reacting an
N-nitroso derivative of an N-substituted nitrile of an ~-amino
acid of formula (II):
R - N - CH - Rl (II)
N C _ N
~0
wherein R and Rl are as defined above, with an acylation
agent selected from the group consisting of haloanhydrides
of carboxylic acids, anhydrides of carboxylic acids and
arylisocyanates, in an organic solvent medium in the pre-
sence of a basic catalyst followed by isolation of the
product of formula (I).
- 3

~765~
Psychostimulating activity of the compounds according
to the present invention has been tested in experiments with
mice and rats.
The experiments are performed with white male mice
with a weight of 18-20 g and with white rat males with a weight
of 120 to 140 g with the account of parameters characterising
the influence of the compounds according to the present inven-
tion on the central nervous system as well as toxicity.
Following this objective, there have been studied:
(1) effect of the compounds on khe locomotory acti-
vity of the animals (locomotory activity is registered using
the instrument "Animex"),
(2) capability of the compounds of inducing stereo-
typic behaviour reactions;
(3) capability of enhancing a reflex excitability
of the animals with respect to the use of tactile stimuli
(air jet pointed from a syringe to an animal),
(4) acute (24-hours) toxicity of the compounds in
individually kept mice and mice placed into standard cages
by 10 animals in each cage, l.e. so-called "group toxicity",
To quantitatively evaluake the central stimulant
activity of the compounds in the:testson mice the values of
ED200 (locomotion) are determined, l.e. doses in which the
compounds cause a two-fold potentiakion of locomotory acti-
vity of the animals; in the tesks performed wikh rats there
are determined values of ED50 (stereotypy~, i.eO doses in
: which the compour-ds, one hour after their administration,
cause, in 5~/O of the test rats, stereotypic behaviour reactions
(ED 0 doses are calculated by the Litchfield and Wilkoxsons
method),
The compounds according to the present invention
_ 4 --

~7~
are sparingly soluble in water. They were administered to
the animals in the form of a suspension prepared with the use
of a 1% solution of carboxymethylcellulose with the addition
of Twin-80 as an emulsifying agent. Since molecular weights
of the test compounds differ from each other, their doses are
calculated in mcM/kg.
The compounds according to the present invention
provide an exciting effect in the central nervous system which
is demonstrated in mice and rats by an enhanced locomotory
acitivity thereof. Thus, minimal doses, which permanently
cause a pronounced locomotory hyperactivity in the animals,
of the above-mentioned compounds of the formula (1), wherein
R is PhCH2CH2 or R is d,l -PhCH2(C~3)CH; with Rt = H and
X ~ NHC6H4Cl - para, or X = NHC6H3C12-meta, para - are 7 to
10 mcM/Xg, while for the compounds of the formula (1) with
R = d,1 -PhCH2(CH3)CH, R' = H, at X = NH-C6H4CF3-meta or
X = NH-C6H4CH3-para and for the compounds of the formula (1)
6 5 2 2' H, X = NH-C6H4CF3-meta, minimal
active doses are 15 to 20 mcM/kg. The simulant effect of
these doses is observed after 10-15 rninutes after administra-
tion reaching its maximum after 30-50 minutes at a total
duration of the effect of 1.5-2 hours. when these doses are
increased by 3-4 times (with mice) and 1~5-2 times Iwlth rats),
the intensity and duration of the locomotory hyperactivity is
also increased. Further increase in doses results in the
origination of stereotypic behaviour reactions with the
animals which is manifested by swing motions of the head and
fore limbs, smelling and licking the case floor. The stereo-
typy duration at high-doses is 6 to 8 hours.
In a special series of experiments there has been
made a quantitative comparison of the central stimulant effect

~71~
of the compounds according to the present invention as deter-
mined by tests of locomotory activity with rnice and stereotypy
with rats. Certain results of these experiments are presented
in the following Table.
Table
Activity of the compounds of the formula (1): R=d,l C6H5CH2
(CH3)CH RT=H, as by tests for locomotory excitation with mice
(ED200) and stereotypic behaviour with rats (ED50).
.. . ... , _ . . . ........... _
Compounds of the present ED2oo(locomo- ED50 (stereotypy),
invention tion)for mice, for rats, mcM/kg
mcM~kg
of the formula ~1),
wherein:
X = NH-C6H4Cl - para 18.2 20.0
X iS NH-C6H~-CF3 - meta 32.3 39.9
,
The compound of the formula (1) according to the
present invention, wherein R is 1 -PhCH2(CH3)CH, R' = H,
X =NHC6H5 in doses of from 3 to 5 mcM/kg causes a moderate
tactile hyperreflexia and in doses of from 6 to 8 mcM~kg ~ an
acute tactile hyperreflexia. The latter is clearly pronounced
with mice-by a series of strong sudden jumps occurring right
at the moment of contact with the air jet, Within the doses
range of from 9 to 80 mcM/kg this compound increase the
locomotory activity of mice in the direct relationship be-tween
this effect value and dose logarythm~ The locomotory activity
value is doubled upon administration of the dose of ED200
within the range of from 30 to 35 mcM/kg. With the dose of
~0 mcM/kg, the increase in the locomotory activity reaches
- its ma~imum within 20 to 30 minutes after the compound
-- 6 --

administration and is maintained at this level during the next
5 hour.
In tests on mice, minimal lethal doses (i.e. doses
killing 10 to 200/o of the test animals) of the compounds accord-
ing to the present invention are within the range of from 200
to 2,000 mcM/kg which is by 25-100 times higher than the
dosage causing a clearly pronounced pharmacological activity -
locomotory hyperractivity-of mice. It should be noted that
toxicity of the compounds is not increased upon administration
of the test compounds to the group-housing animals, i.e. there
is no phenomenon of "group toxicity" which is characteristic
for a series of known psychostimulant compounds such as
amphetamine or dextramphetamine.
Therefore, the compounds according to the present
invention are low-toxic and in small doses cause an intensive
excitation of animals which is characteristic of psychostimu-
lant preparations.
Known in the art is a derivative of sydnonimine,
i.e. d,l-N-phenylcarbamoyl-3-(~-methyl- ~-phenylethyl) syndo-
nimine which also possesses a psychostimulant activity. Com-
parison of this prior art compound with those of the present
-invention shows however, that the novel compounds according
to the present invention are 2-4 times as active as those of
the prior art in experiments with animals. Thus, a known
compound, i.e. d,l-~-phenylcarbamoyl-3-(~-methyl- ~- phenyl-
ethyl) sydnonimine is characterised by values of ED200 of
7~.6 mcM/kg (for locomotion3 and ED50 of 107.1 mcM/~g (for
stereotypy), thls means that to achieve the same pharmacologi-
cal effect, it is necessary to administer doses 2-4 times as
high as those of the compounds according to the present
invention.
-- 7 --

Most active among the compounds according to the
present invention are:
N-para-chlorophenylcarbamoyl-3-( ~ -phenylethyl) sydnonimine
of the formula:
-CH2 - CH2 - N - fH
N + C = N - C - NH - ~ -Cl
O O
and d,l-N-para-chlorophenylcarbamoyl-3-( ~ -methyl- ~- phenyl-
ethyl)-sydnonimine of the formula:
-CH2 - CH - N - CH
CH3 N + C = N - C - NH - ~ - Cl
O O
The novel compounds, viz. N~acylderivatives of
sydnonimine according to the present invention are prepared
by reacting N-nitrosoderivatives of N-substituted nitriles of
~- aminoacids of the formula:
R - N - CH - R'
N~ C - N (lI)
wherein R is phenyl, ~ -phenylethyl, d,l - ~ -methyl- ~ -
phenylethyl, 1- ~ -methyl~ phenylethyl; R' is H, phenyl,
when Rl is phenyl, R is phenyl only, with an acylation agent
in a solvent medium in the presence of a basic-character
catalyst, followed by isolation of the desired product~ As
the acylation agent it is advisable to use haloanhydrides,
anhydrides of carboxylic acids or arylisocyanates. It is
preferable to use, as the solvent, benzene, toluene, di-
chloroethane. As the catalyst use can be made of

various bases, however, it is better to use, as the catalyst,
triethylamine, dimethylbenzylamine, N-methylmorpholine. The
réaction is conducted both at room temperature and upon heating,
dependiny on the acylation agent activity. It is preferable
to conduct the reaction at a temperature within the range of
between 40 to 60C.
The method according to the present invention is
performed in the following manner.
To a solution of N-nitrosoderivatives of ~-sub-
stituted nitriles of ~ -aminoacids of the formula (II) there
are added a basic-character catalyst and an acylation agent.
The reaction mixture is preferably heated to a temperature
within the range of from 40 to 60C to accelerate the process.
On completion of the reaction the desired product
is recovered from the reaction mass by conventional methods.
As the acylation agents in the reaction according
to the present invention varlous electrophylic reagents can
be used such as anhydrides and chloroanhydrides of carboxylic
acids, arylisocyanates. As the catalyst use can be made of
various bases; it has been found that most suitable for the
acceleration of the reaction is triethylamine; slightly slower
the reaction proceeds in the presence of dimethylbenzylamine,
N-methylmorphoIine; use can be also made of other bases such
as imidazole, pyridine, quinoxaline and the like. The reaction
speed substantially depends on the solvent employed while
being increased (in the aase of triethylamine as the catalyst)
in the serieso chloroform >hexane ~toluene > benzene >chloro
benzene > O-dichlorobenze > 1,2-dichloroethane >nitrobenzene.
It is preferred to use toluene or benzene, since the starting
compounds are well soluble in these solvents, whereas the
reaction products, i.e~ corresponding N-acylderivatives of

sydnonimine, are not soluble, as a rule, in these particular
solvents, wherefore they are precipitated in their pure form.
The reaction can occur in water, but in this case the
acylation agent vigorously reacts with water, for
-- 10 --

~ ~ 7$~
this reason~ it is more suitab~e ~o conduct the reaction in
orga~ic hydroxyl-frae solvents.
~he reaction can be per~orm~d a-t room tempera-ture, espe-
cially in the case o-~ active acylation agents; however, the
process rate is rapidly increased with increasing ternperature.
At high temporatures there may occur a thermal decomposition
of the starting nitrosoderivative, wherefora it is pre~era~le
to carry out the process at a temperature within an optimal
range o~ ~rom 40 to 60C. The desired product yie~d ranges
from 80 to 90~0 o~ the theoretical~
~or a ~etter ùnderstanding o~ the present inven~ion9
some specific ~xamples illu~trating the method ~or preparing
the nove~ N-acylderivative~ o~ sydnonimine are given herein-
be~ow.
~amp~.e 1 c;~ /
B To a so~utio~ of 5 g o~ ~ N-n~troso-N-~c~-methy~
ph~ny~ethy~)-aminoaceto~itri~e in 70 m~ o~ dr~ benzene thsre
are added 6.7 ml o~ triethy:Lami:~e and 5095 m~ of acetic an-
hydride. ~ter heatixlg :e02 3 ho~s ~ the temparatslra o~
50C the xeaction mass is avapora~ed to dr~e~s; the residue
is ground with et:he:r; the preclpitate is filtered-off,washad
with water to give 5~3 g (83.5%) o~ acet7~-3~(cC~
met~ pheny~et~l)s~dno~ a m~lti~s a~ 98 99~C. ~olmd,
%: C 63,46; H 6018; N 17~040 C,~3~15~302~ CalU~ateds %:
C 63.60; H 6.16 ~ 17c12,

~7~5~
Example 2
To a solution of 1 g of d,l-N-nitroso-N-phenyl-~-
aminophenylacetonitrile in 10 mllof dry benzene there are
added 1.15 ml of triethylamine and 0.49 ml of benzoyl chloride.
r~he mixture is stirred for 3 hours at the temperature of 50C,
the residue is treated with dry ether, the precipitate is
filtered-off and washed with water. The yield of N-benzoyl-
3,4-diphenylsydnonimine is 0.87 g, melting point is le5-187C
(with decomposition). Found, %: C 73.75 H 4.46 N 11.73.
C21H15N302. Calculated, %: C 73.gO H 4.44 N 12.31.
Example 3
To a solution of 0.70 g of l-N-nitroso-N-(~-methyl-
-phenylethyl)aminoacetonitrile in 7 ml of dry benzene there
are added 0.65 ml of triethylamine and 0.42 ml of phenyliso-
cyanate; after 3 hours, the reaction mass is heated, to the
temperature of 50C, then it is cooled, the precipitate is
filtered-off, washed with benzene, dried and recrystallized
from isopropanol to gi~e 0.96 g (86.5%) of the desired product
i.e. 1-3-(~-methyl- ~ -phenylethyl)-N-phenylcarbamoylsydnoni-
mine comprising a white powder with a yellowish tint sub-
stantially insoluble in water but soluble in fats, acetone,
chloroform: its melting point is 150 152C (with decomposi-
tion), specific rotation ~= -254~5 (acetone,c=l~; it has
three maximum points in UV-spectrum: ~max = 204 mn, 259 nm,
341 nm (ethanol). Found,%: C 67~41 H 5.74 ~ 17.23.
C18H18~402. Calculated,%: C 67.06 H 5.63 N 17.38.
- 12 -

Example 4
A solution o~ 2003 g (0.01 mo~) of` ~7~(T~ ~itroso-~-
-( oC methy~- ~ pheny~ethyl) aminoacetonitril~, 1.54 g (0.01
mol) of paxa-chlorophenylisoc~anate and 1041 ml (0.01 mol~
o~ tri~thylamin0 in 20 m~ o~ dry benzene is heated for 4
hours a-t the temperature o~ 50QC; then the so~ution is coolod,
the precipitate is6~ ~ter~d-o~9 wash0d with benze~e to give
3.0 g (85.4%) o~ N-para-chloro~hen~lcarbamo~l-3-( ~ -
methy~ phenyle~hyl)sydnonimineg melting at 128-130C
(decompositionj. ~ou~d, %: C 6Q60 H 4.92 N 15.47.
C1gH17ClN402~ CaLculat0dg 50 C 60o59 l:I 4 79 N '15 70
IR-spectrum, cm ~: 1,64~; 1,590, 1,530; 3~140~ ~R-spectrum
(in CDCl2 relative to ~S)~ ~8.10 ppm; 9.30 ppm.
Examp~ 5
r~he process is conducted inz.~anner similar to that
described in the foregoing E~ample 49 e~cept that as the
cat~st use is made o~ 5 m~ o~ dimethy~b~nzylamine (instead
o~ triethy~ami~e); th~ ~ield o~ thc dasired pro~uct is 85~o by
weight of th~ theoretical va~ue~
E~ampl~ 6
The proc3~ ~s conducted i~ a ma~ner simi~ar to that
described i~ ~xamp~e 4 hsreLnbe~ore~ e~cept that as ths cata-
lyst u~e is made o~ 6 m~ o~ N-m~thylmorpho~i~o ~i~stsad of
triethylamine~; th~ ~ield o~ th~ desired product is 85% o~
the theoretical valuQ.
: - 13 -
.. . . ...
- . : . ,
' ' ' ~ , ''
.. - , . : . .. .. :
. . . ... . .. . .. . . . . . ..
"
.
.

~LQ'a7~i59
Example 7
d,l-~-nitroso~ methyl- ~ -phenylethyl)amino-
acetonitrile is reacted with meta-, para-dichlorophenyliso-
cyanate following the procedure described in the foregoing
Example 4 at the temperature of 40C. There is obtained
d,l-meta, para-dichlorophenylcarbamoyl-3-(~-methyl- ~ -phenyl-
ethyl)sydnonimine; the yield is 88% of the theory, melting
point is 128-129C (with decomposition). Found, %: C54.92,
18 16 2 4 2- Calculated, % C 55.20,
H 4.13 N 14.31 IR-spectrum, cm : 1,645; 1,580; 1,515. PMR-
spectrum (in CDC13 relative to TMS)~ 8.12, 9.52 ppm.
Example 8
d,l-N-nitroso-N-(~-methyl- ~ -phenylethyl)amino-
acetonitrile is reacted with meta -trifluoromethylphenyl-
isocyanate in a manner similar to that described in Example 4
hereinbefore. There is obtained d,l-N-meta -trifluoromethyl-
phenylcarbamoyl-3-( ~-methyl- ~ -phenylethyl)sydnonimine;
the yield is 81.5% of the theory; melting point is
150-152C (with decomposition). Found, %: C 58.22; H 4.10,
N 14.26. ClgH17F3N4O2. Calculated, %: C 58.50, H 4.39;
N 14.37. IR-spectrum, cm : 1,642, 1,595; 1,540: 3,168. PMR-
spectrum (in CDC13, relative to TMS) ~: 8.14, 9.56 ppm.
Example 9
N-nitroso-N-( ~ -phenylethyl)aminoacetonitrile is
reacted with meta-para-dichlorophenylisocyanate following
the procedure described in Example 4 hereinbefore. There is
obtained N-meta-, para-dichlorophenylcarbamoyl-3-( ~-phenyl-
- 14 -
'' . .' ' ' .. : .

~C~7~9
ethyl)sydnonimine, the yield is 85.5% of the theory, melting
point is 137-138C (with decomposition). Found, %- C 54.26,
; 17 14 2 4 2
H 3.74, N 14.85. IR-spectrum, cm : 1,653, 1,580; 1,510.
PMR-spectrum (in CDC13 relative to TMS),~: 8.08, 9,52 ppm.
Example 10
N-nitroso-N- ( ~-phenylethyl)aminoacetonitrile is
reacted with meta-trimfluoromethylphenylisocy~nate following
the procedure described in the foregoing Example 4 to give
N-meta-trifluorophenylcarbamoyl-3~ phenylethyl)-sydnoni-
mine; the yield is 82.2% of the theoretical value; melting
point is 143-14SC (with decomposition). Found, %: C 57.50;
18H15F3N402. Calculated, %: C 57 30;
H 4.02; N 14.89. IR-spectrum, cm : 1,640; 1,595, L,538;
3,165. iPMR-spectrum (in CDC13 relative to TMS), ~ 8.12;
9.52 ppm.
Example 11
d,l-N-nitroso-N~ methyl~ ~-phenylethyl)aminoaceto-
nitrile lS reacted with para-tolylisocyanate following the
proced~re described in Example 4 hereinbefore-at~the tempera-
ture of 60CC. There is obtained d,l-N-para-tolylcarbamoyl-3-
(~-methyl- G~phenylethyl)sydnonimine, the yield is 85% of the
theoretical value; melting point is 128-130C (with decomposi-
tion). Found, %: C 67,67, H 5.91; ~ 16.62. ClgH20N4O2.
Calculated, %: C 67.91; H 5.93; ~ 16.63. IR-spectrum, cm 1
1,645; 1,595; 1,540. PMR-spectrum (in CDC13 relative to TMS)
~ 8.10; 9.07 pp~.
.
- 15 -

5~
Example 12
The -orocess is conductsd in a manner simi~ar to tha~
described i~ Exa~ple 4~ 0xcept that toluene is used as a sol-
vent. ~ho yield of the dasired product is 86~ of the theore-
tical value.
Ex~nple 13
~ h~ process is conducted in a manner similar to that
described in the foregoing Examp~e 4, e~cept that dry dichlo-
roetha~e is used as a so~vent. On co~pletion of the reaction
the reactio~ mass is ev~porated to dryness; the residue is
ground in ether, ~i~tered-o~X and recr~sta~lized from iso-
propano~. ~he yield of the desired product is 80% of the
theoretical value.
~ 16 -
~ ., ' ' - ' ' ,
: -
,
,
,. ,,: