Cyclic phosphoric acid amide esters, and an insecticide containing the same as active ingredient

The present invention relates to novel cyclic phosphoric acid amide esters, a process for producing the same and an insecticide containing the same as active ingredient. The present invention provides novel 4-substituted-1,3,2-oxazaphospholidine derivatives of the general formula: ##STR1## wherein R.sub.1 represents an alkyl, alkenyl, alkynyl, aralkyl, aralkenyl or aralkynyl group and R.sub.2 represents an alkyl group. The compounds of the formula I may be produced by the reaction of a compound of the formula: ##STR2## wherein R.sub.1 is as hereinbefore defined or an alcoholate thereof with a compound of the formula: ##STR3## wherein R.sub.2 is as hereinbefore defined and X.sub.1 and X.sub.2, which may be same or different, each represents an atom or group removable as an anion. The compounds of the formula I have interesting insecticidal activity particularly against houseflies, adzuki-been weevil, mulberry mealy bug etc.

The present invention relates to novel cyclic phosphoric acid amide esters 
and to processes for their preparation. These compounds possess 
interesting insecticidal activity. 
Certain cyclic phosphoric acid amide esters have been described in the 
literature. Thus for example British Patent Specification No. 763 485 
describes compounds having insecticidal activity of the formula: 
##STR4## 
wherein X.sub.A is an oxygen or sulphur atom, R.sub.A is a hydrogen atom 
or an alkyl group, R.sub.B is an alkyl group and R.sub.C is an alkyl 
group. The Bulletin of The Chemical Society of Japan, Vol. 39, 1296-1297 
(1966) describes a process for producing cyclic phosphoric acid amide 
esters of formula: 
##STR5## 
wherein X.sub.B is an oxygen or sulphur atom, R.sub.D is a hydrogen atom 
or a methyl group and R.sub.E is an alkyl group, but discloses no use for 
these compounds. 
The present invention is based on the discovery that certain novel 
4-substituted cyclic phosphoric acid amide esters posess interesting 
insecticidal activity. 
Thus according to one feature of the present invention there are provided 
compounds of the general formula: 
##STR6## 
wherein R.sub.1 represents an alkyl, alkenyl, alkynyl, aralkyl, aralkenyl 
or aralkynyl group and R.sub.2 represents an alkyl group. 
The compounds of the present invention include an asymmetric carbon atom 
and thus exist in the form of optically active isomers as well as in the 
form of a racemic mixture. All such forms of the compounds of formula I 
are included within the scope of the present invention. 
The compounds of the present invention possess interesting insecticidal 
activity and compounds of the invention which have been tested have been 
found to possess good activity against, for example, houseflies, 
greenhouse whiteflies, mulberry mealy bugs and adzuki-bean weevils. 
Preferred compounds according to the present invention, by virtue of their 
particularly favourable insecticidal activity, include compounds of 
formula I wherein R.sub.1 represents an alkyl, alkenyl or alkynyl group 
with not more than 6 carbon atoms, or an aralkyl, aralkenyl or aralkynyl 
group with 7 to 11 carbon atoms, the aryl moiety of which may optionally 
be substituted by at least one alkyl or alkoxy group with 1 to 4 carbon 
atoms or a halogen atom and R.sub.2 represents an alkyl group with 1 to 6 
carbon atoms. Such preferred compounds include, for example, compounds of 
formula I wherein R.sub.1 represents an alkyl group with 1 to 4 carbon 
atoms or a benzyl group and R.sub.2 represents an alkyl group with 1 to 3 
carbon atoms. 
Especially preferred compounds according to the present invention by virtue 
of their especially favourable insecticidal activity include the 
following: 
(4S)-2-Ethoxy-4-methyl-1,3,2-oxazaphospholidine-2-sulphide; 
2-Ethoxy-4-ethyl-1,3,2-oxazaphospholidine-2-sulphide; 
(4S)-2-Methoxy-4-isopropyl-1,3,2-oxazaphospholidine-2-sulphide; 
(4S)-2-Ethoxy-4-isopropyl-1,3,2-oxazaphospholidine-2-sulphide; 
(4S)-2-Ethoxy-4-sec-butyl-1,3,2-oxazaphospholidine-2-sulphide; 
(4S)-2-Methoxy-4-isobutyl-1,3,2-oxazaphospholidine-2-sulphide; 
(4S)-2-Ethoxy-4-isobutyl-1,3,2-oxazaphospholidine-2-sulphide; 
(4S)-2-Ethoxy-4-benzyl-1,3,2-oxazaphospholidine-2-sulphide; 
(4R)-2-Methoxy-4-isobutyl-1,3,2-oxazaphospholidine-2-sulphide. 
According to a further feature of the present invention there is provided a 
process for the preparation of compounds of formula I as hereinbefore 
defined which comprises reacting a compound of the formula: 
##STR7## 
wherein R.sub.1 is as hereinbefore defined or an alcoholate thereof with a 
compound of the formula: 
##STR8## 
wherein R.sub.2 is as hereinbefore defined and X.sub.1 and X.sub.2, which 
may be the same or different, each represents an atom or group removable 
as an anion whereby a compound of formula I is obtained. 
A compound of formula III is advantageously used in which X.sub.1 and 
X.sub.2, which may be the same or different, each represents a halogen 
atom. Preferably a compound of formula III is used in which X.sub.1 and 
X.sub.2 each represent a chlorine atom. 
The reaction is conveniently effected in the presence of a base, this being 
especially preferred when a compound of formula II as opposed to the 
corresponding alcoholate is used. 
The process of the present invention is conveniently effected using a 
compound of formula II in which R.sub.1 represents an alkyl group with 1 
to 6 carbon atoms or an aralkyl group with 7 to 11 carbon atoms. R.sub.1 
in the compounds of formula II may be straight and/or branched chain and 
may include unsaturated bonds. Where R.sub.1 in the compound of formula II 
represents an aralkyl group the aryl moiety e.g. the benzene ring may 
include alkyl groups having from 1 to 4 carbon atoms, alkoxy groups or 
halogen atoms as substituents. The alkyl moiety of the aralkyl group may 
be straight or branched chain, and may also include unsaturated bonds. 
Compounds of formula II which may, for example, be employed in the 
processes of the present invention, depending upon the compound of formula 
I to be prepared, have the boiling points and specific rotations set out 
in the following Table 1. 
TABLE 1 
__________________________________________________________________________ 
Compound of Boiling or 
the formula [II] 
Formula melting point 
[.alpha.].sub.D.sup.25 
__________________________________________________________________________ 
(2S)-2-amino- propanol (alaninol) 
##STR9## 65.degree.-67.degree. C./ 10 mmHg 
+22.5 (C = 15 in dioxan) 
(2S)-2-amino-3- methylbutanol (valinol) 
##STR10## 91.degree.-92.degree. C./ 10 mmHg 
+14.5 (C = 12 in dioxan) 
(2S)-2-amino-4- methylpentanol (leucinol) 
##STR11## 90.degree.-92.degree. C./ 11 mmHg 
+3.0 (C = 20 in ethanol) 
(2S)-2-amino-3- methylpentanol (iso-leucinol) 
##STR12## 108.degree.-109.degree. C./ 13 mmHg 
-3.5 (C = 20 in ethanol) 
2-aminobutanol 
##STR13## commercial product 
racemic compound 
(2S)-2-amino-3- phenylpropanol (phenylalaninol) 
##STR14## m.p. 90.degree.-91.degree. C. 
-25.8 (C = 10 in ethanol) 
(2R)-2-amino-4- methylpentanol (D-leucinol) 
##STR15## 92.degree.-93.degree. C./ 10 mmHg 
[.alpha.].sub.D.sup.20 = -4.79 (C = 11.7 in 
benzene) 
__________________________________________________________________________ 
The compound of formula II used in the processes of the present invention 
may be in optically active or racemic form depending upon the compound of 
formula I which it is desired to prepare. 
A compound of formula III may for example be used in processes of the 
present invention in which R.sub.2 represents a methyl, ethyl or propyl 
group depending upon the compound of formula I which it is desired to 
prepare. 
Bases which may conveniently be used in the processes of the present 
invention include organic bases e.g. tertiary organic bases such as 
triethylamine and pyridine. Where the base employed is a liquid the base 
may, if desired, additionally serve as the solvent. 
The reaction is conveniently effected in the presence of an inert solvent 
which thus does not react with the starting compounds and may be used 
either along or in combination with other inert solvents as the solvent 
for the reaction. Preferred organic solvents include dioxan, benzene, 
toluene, xylene or chloroform. In order to avoid side reactions it is 
advantageous to conduct the reaction in the absence of water and it is 
thus convenient to use an anhydrous solvent or a solvent which has been 
dried. The reaction is preferably effected at a temperature of from 
-10.degree. to +10.degree. C. In order to keep the reaction temperature 
below 10.degree. C., the reaction vessel is preferably cooled with ice. 
The reaction time is usually from one to three hours. The compound of 
formula II or the alcoholate thereof is conveniently used in a 
concentration of from 0.05 to 0.5 mol/liter of the compound used as 
solvent. An equimolar amount or molar excess e.g. a slight molar excess of 
the compound of formula III is conveniently used per mole of the compound 
of formula III or the alcoholate thereof. 2 to 2.2 Mols of base are 
preferably used per mole of the compound of formula II or alcoholate 
thereof. 
In a preferred embodiment of the process of the present invention the 
reaction is conducted by dissolving the alkylphosphorodichlorido thionate 
of formula III in a reaction solvent and adding the solution thus obtained 
to the reaction vessel. Then the aminoalcohol of formula II and the base, 
both dissolved in a reaction solvent, are added dropwise with agitation to 
the mixture in the reaction vessel. It is possible if desired to reverse 
the order of the addition. The reaction product obtained is isolated from 
the reaction mixture and purified in the following manner:- 
After completion of the reaction, the salt formed with hydrogen chloride 
and the base is separated out from the reaction mixture by filtration. The 
filtrate is concentrated, followed by evaporation under reduced pressure 
or by column-chromatography. In this manner, the desired product is 
isolated and purified. Certain products obtained by this method and their 
physical properties are shown in Table 2. 
TABLE 2 
__________________________________________________________________________ 
Substituents 
Compound in formula [I] 
Boiling 
No. 
Name R.sub.1 R.sub.2 
point(.degree.C.) 
[.alpha.].sub.D.sup.25 
__________________________________________________________________________ 
1. (4S)-2-ethoxy-4-methyl-1,3,2- 
CH.sub.3 C.sub.2 H.sub.5 
105-107/ 
+15.20 
oxazaphospholidine-2-sulphide 
0.05 mmHg 
(C = 5 in ethanol) 
2. 2-ethoxy-4-ethyl-1,3,2- 
C.sub.2 H.sub.5 
C.sub.2 H.sub.5 
105-106/ 
racemic compound 
oxazaphospholidine-2-sulphide 
0.005 mmHg 
3. (4S)-2-methoxy-4-isopropyl-1,3,2- oxazaphospholidine-2-sulphide 
##STR16## 
CH.sub.3 
107-108/ 0.006 mmHg 
not measured 
4. (4S)-2-ethoxy-4-isopropyl-1,3,2- oxazaphospholidine-2-sulphide 
##STR17## 
C.sub.2 H.sub.5 
110-111/ 0.04 mmHg 
-8.12 (C = 5 in ethanol) 
5. (4S)-2-ethoxy-4-sec-butyl-1,3,2- oxazaphospholidine-2-sulphide 
##STR18## 
C.sub.2 H.sub.5 
123-124/ 0.05 mmHg 
-3.46 (C = 5 in ethanol) 
6. (4S)-2-methoxy-4-isobutyl-1,3,2- oxazaphospholidine-2-sulphide 
##STR19## 
CH.sub.3 
115-116/ 0.03 mmHg 
+1.22 (C = 5 in ethanol) 
7. (4S)-2-ethoxy-4-isobutyl-1,3,2- oxazaphospholidine-2-sulphide 
##STR20## 
C.sub.2 H.sub.5 
120-121/ 0.05 mmHg 
-4.73 (C = 20 in ethanol) 
8. (4S)-2-ethoxy-4-benzyl-1,3,2- oxazaphospholidine-2-sulphide 
##STR21## 
C.sub.2 H.sub.5 
not measured 
-15.14 (C = 5 in ethanol) 
9. (4R)-2-methoxy-4-isobutyl-1,3,2- oxazaphospholidine-2-sulphide 
##STR22## 
CH.sub.3 
115-116/ 0.03 mmHg 
not measured 
__________________________________________________________________________ 
Insectcidal experiments were carried out by using as test insects, 
houseflies (Musca domestica vicina) of various strains such as for example 
Takatsuki-strain, Misaki-strain etc., adzuki-bean weevil (Callosobruchus 
chinensis), greenhouse whitefly (Trialeudes vaporariorum) and mulberry 
mealy bug (Pseudococcus comstocki). 
In these experiments, Sumithion [fenitrothion viz. 
dimethyl-(3-methyl-4-nitrophenyl)-thiophosphate; commercially available 
from Sumitomo Kagaku Kogyo K.K., Japan], salithion 
[2-methoxy-4H-1.3.2-benzodioxaphosphorine-2-sulphide] and diazinon 
[O,O-diethyl O-(2-isopropyl-4-methyl-6-pyrimidinyl)-phosphoro-thionate], 
which all possess insecticidal activity were used for comparative 
purposes. A control containing no active ingredient was also used. 
As a result of these tests, it can be seen that 
4-substituted-1,3,2-oxazaphospholidine derivatives according to the 
present invention possess interesting insecticidal activity. 
(A) Insecticidal experiments using houseflies: 
(A-1) Mortality by topical application method: 
Adults of houseflies (female) of the Takatuski strain were treated with 
individual insecticidal samples by conventional topical application, after 
3-5 days from emergence. The activity was evaluated by mortality measured 
after 24 hours from the application. For comparison, Sumithion was used to 
give the results shown in Table 3. 
TABLE 3 
______________________________________ 
Insecticidal activity against housefly 
Compound 
Applied amount (.mu.g/one female) 
No. 100 10 5 1 0.5 0.1 0.05 
______________________________________ 
1 100 100 70 0 0 0 0 
2 100 100 100 10 0 0 0 
3 100 100 100 100 100 60 20 
4 100 100 100 80 20 0 0 
5 100 100 100 100 20 0 0 
6 100 100 100 100 100 10 0 
7 100 100 100 90 50 0 0 
8 100 100 20 10 0 0 0 
9* 100 100 100 100 100 80 10 
10** 0 0 0 0 0 0 0 
______________________________________ 
Notes: 
*Sumithion 
**Control? 
(A-2) LD.sub.50 : 
Adults of female houseflies of the Takatsuki strain and the Misaki strain 
were topically treated after 3-5 days from emergence, with individual 
samples in conventional manner. After 24 hours from the application, the 
LD.sub.50 was determined and the results are shown in Table 4. Sumithion 
was used for comparative purposes. 
(A-3) KT.sub.50 (Median knock-down time): 
Adults of female houseflies of the Takatsuki strain and the Misaki strain 
were treated with individual samples, after 3-5 days from emergence, by 
placing them in contact with a film formed with a residual sample (200 
.mu.g) in a cup in conventional manner (the so called dry film method). 
Median knock-down time (50%) was measured, as shown in Table 4. Sumithion 
was again used for comparison purposes. 
TABLE 4 
______________________________________ 
Insecticidal activity against housefly 
Housefly 
Takatsuki-strain Misaki-strain 
Compound 
LD.sub.50 KT.sub.50 LD.sub.50 
KT.sub.50 
No. (.mu.g/female) 
(min) (.mu.g/female) 
(min) 
______________________________________ 
1 16 60 3.5 -- 
2 1.5 41 ** -- 
3 0.16 20 0.14 11.5 
4 1.2 37.5 0.68 -- 
5 1.07 39 1.2 -- 
6 0.23 18 0.29 12 
7 1.00 31 1.12 15 
8 2.16 &gt;200 2.35 -- 
9 -- -- 1.06 -- 
10* 0.09 22 10.03 &gt;240 
______________________________________ 
Notes: 
*Sumithion 
**100% at 30 .mu.g/female 
(A-4) Insecticidal activity against houseflies of various strains: 
Adults of female houseflies of various strains shown in Table 5 were 
topically treated with individual samples in conventional manner after 3-5 
days from emergence to give the results shown in Table 5. LD.sub.50 
(.mu.g/female) was determined after 24 hours from the application. For 
comparative purposes, Sumithion and diazinon were used. 
TABLE 5 
______________________________________ 
Insecticidal activities against 
houseflies of various strains [LD.sub.50 (.mu.g/female)] 
Strain 
Compound Daisan- 
No. Lab-em-7em Yuzawa Yasato 
Yumeno-shima 
______________________________________ 
3 0.066 0.513 0.892 1.225 
6 0.085 0.407 0.585 0.964 
Diazinon 
0.02 0.268 1.600 12.110 
Sumithion 
0.03 -- -- 11.98 
______________________________________ 
(B) Insecticidal experiment using adzuki-bean weevil: 
Adults of the female adzuki-bean weevil were treated with individual 
samples after one day from emergence by the conventional dry film method. 
The mortality was determined after 24 hours from treatment, as shown in 
Table 6. For comparison, Sumithion was used. 
TABLE 6 
______________________________________ 
Insecticidal activity against adzuki-bean weevil 
Compound Residual amount (.mu.g/cup) 
No. 25 10 5 2.5 1 0.5 
______________________________________ 
1 100 100 20 0 0 0 
2 100 100 50 10 0 0 
3 100 100 100 100 100 30 
4 100 100 100 100 10 0 
5 100 100 50 20 0 0 
6 100 100 100 75 0 0 
7 80 60 5 0 0 0 
8 90 20 0 0 0 0 
9* 100 100 100 100 100 20 
10** 0 0 0 0 0 0 
______________________________________ 
Notes: 
*Sumithion? 
**Control 
(C) Insecticidal experiment using greenhouse whitefly: 
Fifty to sixty adult greenhouse whiteflies were made parasitic on the 
leaves of kidney-bean seedlings planted in a pot (diameter 15 cm) in a 
greenhouse. A test sample of a 25% emulsifiable concentrate was prepared 
by mixing compound No. 7 (25 parts by weight), dimethylformamide (20 parts 
by weight), cyclohexane (35 parts by weight) and Solpol (20 parts by 
weight; emulsifier commercially available from Toho Kagaku Kogyo K.K., 
Japan) and was then diluted with water to give a concentration of 250 ppm. 
A 50% emulsifiable concentrate of Sumithion and a 25% emulsifiable 
concentrate of Salithion were also prepared and diluted with water to give 
a 250 ppm concentration for comparison. The leaves of the seedlings were 
thoroughly sprayed with individual solutions to wet the leaves and were 
then allowed to stand for 24 hours. After this, mortality was determined, 
as shown in Table 7. 
TABLE 7 
______________________________________ 
Insecticidal activity against greenhouse whitefly 
Active Concentration Mortality 
ingredient (ppm) (%) 
______________________________________ 
Compound No. 7 
250 98 
Sumithion 250 65 
Salithion 250 100 
______________________________________ 
(D) Insecticidal activity against mulberry mealy bug: 
Each of compounds 3 and 6 (each 25 parts by weight) were mixed with 
dimethylformamide (20 parts by weight), cyclohexane (35 parts by weight) 
and Solpol (20 parts by weight) to form the 25% emulsifiable concentrates, 
each of which was then diluted with water to give a concentration of 500 
ppm. For comparison purposes, a wettable powder of salithion (36% by 
weight/weight) was diluted with water to give a concentration of 360 ppm. 
The diluted samples were individually sprayed over the whole bodies of 
larvae (3rd to 4th instar) of mulberry mealy bug (Pseudococcus comstocki) 
which were then allowed to stand at ambient temperature. Mortality was 
determined after 3 days from application to give the results shown in 
Table 8. 
TABLE 8 
______________________________________ 
Insecticidal activity against mulberry mealy bugs 
Concentration 
Numbers of test 
Mortality 
(ppm) mealy bugs (%) 
______________________________________ 
Compound 3 
500 248 97.6 
Compound 6 
500 227 94.7 
Salithion 
360 261 99.2 
Untreated 
0 127 5.5 
______________________________________ 
According to a still further feature of the present invention there are 
provided insecticidal compositions comprising as active ingredient at 
least one compound of formula I as hereinbefore defined in association 
with an inert carrier or diluent. 
The compounds according to the present invention may, if desired, be 
applied directly to the soil for insecticidal purposes, although it is 
possible to form insecticidal compositions by mixing the compounds with 
conventionally used carriers. Insecticidal compositions in the form of 
powders, wettable powders, emulsifiable concentrates, granules and the 
like may be produced by combining the compounds with, for example, 
carriers in the form of liquids or solids such as surfactants, dispersing 
agents, wetting agents and the like used for agricultural compositions. 
Examples of solid carriers include talc, clay, kaolin, diatomaceous earth, 
white carbon, polyvinylalcohol, wood powder and the like, while preferred 
liquid carriers are exemplified by water, acetone, acetonitrile, toluene, 
xylene, methylphthalene and various other solvents conventionally used for 
the preparation of agricultural compositions. 
According to a yet still further feature of the present invention there is 
provided a method of preventing or inhibiting the growth or proliferation 
of insects which comprises applying to a site infested with or susceptible 
to infestation by insects an effective amount of a compound of formula I 
as hereinbefore defined. 
In use for this purpose, the composition of the present invention contains, 
preferably, from 0.01 to 1% by weight of active ingredient. 
The following non-limitative examples illustrate the invention. 
EXAMPLE 1 
(4S)-2-Ethoxy-4-isobutyl-1,3,2-oxazaphospholidine-2-sulphide 
Ethyl-phosphorodichlorido-thionate (3.56 g; 0.02 mol) and dried dioxan (200 
ml) were poured into a reaction vessel. Separately, L-leucinol 
[(2S)-2-amino-4-methylpentanol] (2.34 g; 0.02 mol) and triethylamine (4 g; 
0.04 mol) were dissolved in dried dioxan (200 ml) which was then added 
dropwise to the solution in the reaction vessel over a period of about 5 
minutes with agitation. The agitation was further continued for about 10 
minutes and then an exothermic reaction was observed. The reaction 
temperature was kept at a temperature below 10.degree. C. by cooling with 
ice. The reaction time was about three hours. After the completion of the 
reaction, the triethylamine hydrochloride formed was removed by 
filtration, and dioxan was also removed by concentration and filtration. 
The residual solution was evaporated under reduced pressure to isolate an 
oily substance (colourless and transparent) in a yield of 56.8%. [In the 
Examples, the yields were calculated on the basis of the amount of 
aminoalcohol used.] 
Boiling point: 120.degree.-121.degree. C./0.05 mmHg. 
[.alpha.].sub.D.sup.25 =-4.73 (C=20 in ethanol). 
______________________________________ 
Elementary analysis (%): 
C H N 
______________________________________ 
Found 43.00 8.45 6.32 
Calculated as C.sub.8 H.sub.18 NO.sub.2 SP 
43.03 8.13 6.27 
______________________________________ 
Molecular weight: 223 (by mass-spectrometry). 
Infrared absorption spectrum (cm.sup.-1) by KBr method: 3400, 2950, 1470, 
1390, 1370, 1290, 1220, 1140, 1070-980, 950, 900 and 840-670. 
NMR spectrum: shown in FIG. 1A. 
The oily substance thus obtained was identified, using this data, as 
(4S)-2-ethoxy-4-isobutyl-1,3,2-oxazaphospholidine-2-sulphide viz. a 
compound of the formula [1] wherein R.sub.1 = an isobutyl group and 
R.sub.2 = an ethyl group. 
EXAMPLE 2 
(4S)-2-Ethoxy-4-methyl-1,3,2-oxazaphospholidine-2-sulphide 
A similar procedure to that described in Example 1 was carried out with the 
exception that L-alaninol (1.5 g; 0.02 mol) was used instead of 
L-leucinol. An oily substance was obtained in a yield of 44.2%. 
Boiling point: 105.degree.-107.degree. C./0.05 mmHg. 
[.alpha.].sub.D.sup.25 =+15.20 (C=5.0 in ethanol). 
______________________________________ 
Elementary analysis (%): 
C H N 
______________________________________ 
Found 33.11 6.84 7.76 
Calculated as C.sub.2 H.sub.12 NO.sub.2 SP 
33.14 6.68 7.73 
______________________________________ 
Molecular weight: 181 (by mass-spectrometry). 
Infrared absorption spectrum (cm.sup.-1) by KBr method: 3400, 2950, 1470, 
1390, 1330, 1290, 1210, 1140, 1070-980, 850, 900, 850-700. 
NMR spectrum: shown in FIG. 1B. 
The oily substance thus obtained was identified, using the above data, as 
(4S)-2-ethoxy-4-methyl-1,3,2-oxazaphospholidine-2-sulphide viz. a compound 
of the formula [1] wherein R.sub.1 = a methyl group and R.sub.2 = an ethyl 
group. 
EXAMPLE 3 
2-Ethoxy-4-ethyl-1,3,2-oxazaphospholidine-2-sulphide 
A similar procedure to that described in Example 1 was carried out with the 
exception that DL-.beta.-aminobutanol (1.78 g; 0.02 mol) was used instead 
of L-leucinol. An oily substance (boiling point: 105.degree.-106.degree. 
C./0.005 mmHg) was obtained. 
Yield: 12.8%. 
______________________________________ 
Elementary analysis (%): 
C H N 
______________________________________ 
Found 37.03 7.03 7.16 
Calculated as C.sub.6 H.sub.14 NO.sub.2 SP 
36.92 7.23 7.17 
______________________________________ 
Molecular weight; 195. 
Infrared absorption spectrum (cm.sup.-1) by KBr method: 3400, 2950, 1470, 
1390, 1310, 1290, 1140, 1070-960, 840-700 
NMR spectrum: shown in FIG. 2A. 
The oily substance thus obtained was identified, using the above data, as 
2-ethoxy-4-ethyl-1,3,2-oxazaphospholidine-2-sulphide viz. a compound of 
the formula [1] wherein R.sub.1 = an ethyl group and R.sub.2 = an ethyl 
group. 
EXAMPLE 4 
(4S)-2-Methoxy-4-isopropyl-1,3,2-oxazaphospholidine-2-sulphide 
The similar procedure to that described in Example 1 was carried out with 
the exception that L-valinol (2.06 g; 0.02 mol) was used instead of 
L-leucinol and that ethylphosphorodichlorido-thionate was replaced with 
methylphosphorodichlorido-thionate (3.28 g; 0.02 mol). An oily substance 
was obtained (boiling point: 107.degree.-108.degree. C./0.006 mmHg) in a 
yield of 10.5%. 
Molecular weight: 195. 
______________________________________ 
Elementary analysis (%): 
C H N 
______________________________________ 
Found 35.89 7.09 6.83 
Calculated as C.sub.6 H.sub.14 NO.sub.2 SP 
36.92 7.23 7.17 
______________________________________ 
Infrared absorption spectrum (cm.sup.-1) by KBr method: 3400, 2950, 1470, 
1390, 1370, 1310, 1290, 1180, 1140, 1070-980, 920, 900, 840-690. 
NMR spectrum: shown in FIG. 2B. 
The oily substance thus obtained was identified, using the above data, as 
(4S)-2-methoxy-4-isopropyl-1,3,2-oxazaphospholidine-2-sulphide. 
EXAMPLE 5 
(4S)-2-Ethoxy-4-isopropyl-1,3,2-oxazaphospholidine-2-sulphide 
A similar procedure to that described in Example 1 was carried out with the 
exception that L-valinol (2.06 g; 0.02 mol) was used instead of 
L-leucinol. An oily substance was obtained in a yield of 57.4%. 
Boiling point: 110.degree.-111.degree. C./0.04 mmHg. 
[.alpha.].sub.D.sup.25 =-8.12 (C=5.0 in ethanol). 
______________________________________ 
Elementary analysis (%): 
C H N 
______________________________________ 
Found 39.90 7.87 6.66 
Calculated as C.sub.7 H.sub.16 NO.sub.2 SP 
40.18 7.71 6.69 
______________________________________ 
Molecular weight: 209. 
Infrared absorption spectrum (cm.sup.-1) by KBr method: 3400, 2950, 1470, 
1390, 1370, 1270, 1140, 1070-980, 950, 840-690. 
NMR spectrum: shown in FIG. 3A. 
The oily substance thus obtained was identified, using the above data, as 
(4S)-2-ethoxy-4-isopropyl-1,3,2-oxazaphospholidine-2-sulphide. 
EXAMPLE 6 
(4S)-2-Ethoxy-4-sec-butyl-1,3,2-oxazaphospholidine-2-sulphide 
A similar treatment to that described in Example 1 was carried out with the 
exception that L-isoleucinol (2.34 g; 0.02 mol) was used instead of 
L-leucinol. An oily substance was obtained in a yield of 49.3%. 
Boiling point: 123.degree.-124.degree. C./0.05 mmHg. 
[.alpha.].sub.D.sup.25 =-3.46 (C=5.0 in ethanol). 
______________________________________ 
Elementary analysis (%): 
C H N 
______________________________________ 
Found 42.98 8.38 6.37 
Calculated as C.sub.8 H.sub.18 NO.sub.2 SP 
43.03 8.13 6.27 
______________________________________ 
Molecular weight: 223. 
NMR spectrum: shown in FIG. 3B. 
The oily substance thus obtained was identified, using the above data, as 
(4S)-2-ethoxy-4-sec-butyl-1,3,2-oxazaphospholidine-2-sulphide. 
EXAMPLE 7 
(4S)-2-Methoxy-4-isobutyl-1,3,2-oxazaphospholidine-2-sulphide 
A similar treatment to that described in Example 1 was carried out with the 
exception that methyl-phosphorodichlorido-thionate was used instead of 
ethyl-phosphorodichlorido-thionate. An oily substance was obtained in a 
yield of 31.5%. 
Boiling point: 115.degree.-116.degree. C./0.03 mmHg. 
[.alpha.].sub.D.sup.25 =+1.22 (C=5.0 in ethanol). 
______________________________________ 
Elementary analysis (%): 
C H N 
______________________________________ 
Found 40.21 8.08 6.72 
Calculated as C.sub.7 H.sub.16 NO.sub.2 SP 
40.18 7.71 6.69 
______________________________________ 
Molecular weight: 209. 
Infrared absorption spectrum (cm.sup.-1) by KBr method: 3400, 2950, 1470, 
1390, 1370, 1340, 1290, 1220, 1180, 1140, 1080-900, 945, 900, and 860-660. 
NMR spectrum: shown in FIG. 4A. 
The oily substance thus obtained was identified, using the above data, as 
(4S)-2-methoxy-4-isobutyl-1,3,2-oxazaphospholidine-2-sulphide. 
EXAMPLE 8 
(4S)-2-Ethoxy-4-benzyl-1,3,2-oxazaphospholidine-2-sulphide 
A similar treatment to that described in Example 1 was carried out with the 
exception that L-phenylalaninol (3.02 g; 0.02 mol) was used instead of 
L-leucinol. The synthesized material was subjected to column 
chromatographic treatment to give an oily substance in a yield of 51.4%. 
[.alpha.].sub.D.sup.25 =-15.14 (C=5.0 in ethanol). 
______________________________________ 
Elementary analysis (%): 
C H N 
______________________________________ 
Found 50.21 6.34 5.27 
Calculated as C.sub.11 H.sub.16 NO.sub.2 SP 
51.35 6.27 5.44 
______________________________________ 
Molecular weight: 257. 
NMR spectrum: shown in FIG. 4B. 
The oily substance thus obtained was identified, using the above data, as 
(4S)-2-ethoxy-4-benzyl-1,3,2-oxazaphospholidine-2-sulphide. 
EXAMPLE 9 
(4R)-2-Methoxy-4-isobutyl-1,3,2-oxazaphospholidine-2-sulphide 
A similar treatment to that described in Example 7 was carried out with the 
exception that D-leucinol (2.34 g; 0.02 mol) was used instead of 
L-leucinol. An oily substance was obtained in a yield of 30.0%. 
Boiling point: 115.degree.-116.degree. C./0.03 mmHg. 
______________________________________ 
Elementary analysis (%): 
C H N 
______________________________________ 
Found 40.25 7.68 6.72 
Calculated as C.sub.7 H.sub.16 NO.sub.2 SP 
40.18 7.71 6.69 
______________________________________ 
Molecular weight: 209 
Infrared absorption spectrum (cm.sup.-1) by KBr method: 3400, 2950, 1470, 
1390, 1370, 1290, 1220, 1180, 1140, 1070-980, 945, 900, and 840-670. 
The oily substance thus obtained was identified, using the above data, as 
(4R)-2-methoxy-4-isobutyl-1,3,2-oxazaphospholidine-2-sulphide. 
The compounds synthesized in the above-mentioned Examples are new 
compounds. 
Synthesis of aminoalcohols: 
The aminoalcohols for use in the preparation of the compounds according to 
the present invention are known from the literature. For example, the 
aminoalcohols shown in Table 1 may be produced in a similar manner to that 
used for the synthesis of L-leucinol, as apparent from the following 
reference wherein the 2-aminobutanol used was a commercial product. 
Reference (Synthesis of L-leucinol) 
Thionyl chloride (100 ml) was added dropwise to ice-cooled absolute ethanol 
(250 ml) which was then stirred at 0.degree. C. for 30 minutes. L-leucine 
(50 g) was added to the solution and was stirred at ambient temperature 
for about 24 hours. The reaction was continued until L-leucine was 
completely dissolved to result in a transparent solution. The solution was 
concentrated under reduced pressure, and the solid substance thus-formed 
was recrystallized from ethanol-ether. White needle-like crystals were 
obtained (melting point: 130.degree.-131.degree. C.) representing 
L-leucine ethyl ester (hydrochloride). Yield 95%. 
L-leucine ethyl ester hydrochloride (40 g; 0.26 mol) was dissolved in 75% 
ethanol (600 ml), which was added dropwise to a 75% ethanol solution (600 
ml) of sodium borohydride [NaBH.sub.4 (38 g; 0.1 mol)]. This reaction 
mixture was allowed to stand at ambient temperature until the generation 
of hydrogen gas became weak. After this, the solution was boiled under 
reflux for 5 hours in a water bath. Ethanol was distilled off under 
reduced pressure, and the resultant aqueous solution was extracted with 
ethyl acetate. The obtained extract was washed with a saturated sodium 
chloride solution and was dried by using anhydrous Na.sub.2 SO.sub.4. 
After removal of ethyl acetate, the solution was concentrated under 
reduced pressure to give a colourless liquid representing L-leucinol 
(boiling point: 90.degree.-92.degree. C./11 mmHg) in a yield of 59.6%.

FORMULATION EXAMPLES 
EXAMPLE A 
Emulsifiable Concentrate 
25 parts by weight of 
(4S)-2-methoxy-4-isopropyl-1,3,2-oxazaphospholidine-2-sulphide was mixed 
with 20 parts by weight of dimethylformamide, 35 parts by weight of 
cyclohexane and 20 parts by weight of Solpol to form a 25% emulsifiable 
concentrate. 
The emulsifiable concentrate was then diluted with water to give a 
composition ready for use having an active ingredient concentration of 500 
p.p.m. 
EXAMPLE B 
Emulsifiable Concentrate 
25 parts by weight of 
(4S)-2-methoxy-4-isobutyl-1,3,2-oxazaphospholidine-2-sulphide was mixed 
with 20 parts by weight of dimethylformamide, 35 parts by weight of 
cyclohexane and 20 parts by weight of Solpol to form a 25% emulsifiable 
concentrate. 
The emulsifiable concentrate was then diluted with water to give a 
composition ready for use having an active ingredient concentration of 500 
p.p.m. 
EXAMPLE C 
Emulsifiable Concentrate 
25 parts by weight of 
(4S)-2-ethoxy-4-isobutyl-1,3,2-oxazaphospholidine-2-sulphide was mixed 
with 20 parts by weight of dimethylformamide, 35 parts by weight of 
cyclohexane and 20 parts by weight of Solpol to form a 25% emulsifiable 
concentrate. 
The emulsifiable concentrate was then diluted with water to give a 
composition ready for use having an active ingredient concentration of 250 
p.p.m.