CA1250849A - N-phenylamino acid esters and their production - Google Patents

Abstract

Abstract:
The present invention is directed to compounds of the formula:

Description

3~

N-Phenylamino Acid Esters and Their Production The present invention has been divided out of Canadian Patent Application Serial No. 492,126 filed October 3, 1935.
This invention rela-tes to novel N-phenylamino acid esters and their production and their use as intermediates in the preparatlon of quinoxalines.
The inven-tion provides compounds of the formula:

O R2 R3 X ¦ ¦
R O-C-lH-l ~ N ~ (I)

2 O

wherein X is a hydrogen atom, a fluorine atom or a chlorine atom, R2 is a hydrogen atom or a methyl group, R is a hydrogen atom or a methyl group and R4 is a Cl 4 alkyl group.
These compounds are useful in the preparation of quinoxalines of the formula.

~~

wherein A is a group of the formula: -CH-N- or -C=N- in which R2 l3 R
R is a hydrogen atom or a methyl group, R3 is a hydrogen atom or a methyl group and the nitrogen atom is bonded to the benzene ring.

3 ~ L~ ~

The quinoxalines are useful as intermediates in the preparation of tetrahydrophthalimides of the general formula:

~A~X~o Ri 1 C5 alkyl group, a C3-C alkenyl C3-C5 alkynyl group or a Cl-C3 alkoxymethyl group, X and A are as defined above.
The compounds of the formula R ~ X )l (I) wherein X, R , R3 and R are as defined above can be prepared by reacting an N-nitrophenylphthalimide of formula (IV) o ~ X ~ (IV) with an amin acid ester of the formula:

HN-CH-COOR (VIII) wherein R , R and R are each as deEined above in an amount of 2.5 to ~ equivalents to one equivalent of the N-nitro-phenylph-thalimide (IV) in a solvent (e.g. dioxane, dimethyl-formamide, dimethylsulfoxide) at a -terr.perature of 50 to 200C.
To obtain the quinoxalinesof the formula (II) the N-phenylarnino acid ester(I)is subjected to reductive cyclization with an appropriate reducing agent, for instance, iron in an acid (e.g. acetic acid) to give the dihydroquinoxalinone (VI) ~3 o,~N~b3 J

More specifically, the N-phenylamino acid ester (I) is treated with 3 to 10 equivalent amounts of powc1ery iron such as electrolytic iron or reduced iron in a solvent (e.g. water, alcohol, acetic acid, ethyl acetate) in the existence of an excessive amount of an acid (e.g. acetic acid, hydrochloric acid) at a temperature of 50 to 200C.
The N-nitrophenylphthalimide (IV) is per se known and obtainable by the method as described in EP-A-0077938A.
Typical examples for production of the compounds (I) and (VI) are illustra-tively shown in the Eollowing Examples.
Example 1 2-(4-Fluoro-3-nitrophenyl)-4,5,6,7-te-trahydro-2H-isoindole-1,3-dione (5.8 g) was added to a mixture of glycine methyl ester hydrochloride (7.5 g), triethylamine (6 g) and r~ J~

1,4-dioxane (50 ml?, and the resultant mixture was heated under xeflux for 4 hours, followed by addition of water and extraction with ethyl acetate. The extract was washed with water, dried and concentrated. The residue was crystallized from methanol to give 2-(4-methoxycarbonyl-methylamino-3-nitrophenyl)-4,5,6,7-tetrahydro-2H-iso-indole-1~3-dione t2.6 g). m.p., 220C.
In the same manner as above, the N-phenylamino acid esters (I) as shown in Table l were obtained:
Table 1 R O-C-CH-N ~ N ~ (I) CompoundX R R3 R4 Physical constant No.
.
a F H H C~2CH3 m.p~ 166.8C
b F H CH3 CH2CH3 m.p., 159.2C
c Cl H H CH2CH3 m.p., 153 - 154 C

Fxample 2 2-(4-Methoxycarbonylmethylamino-3-nitrophenyl)-

4,5,6,7-tetrahydro-2H-isoindole~1,3-dione (2.06 g) was dissolved in a mixture of acetic acid (20 ml) and ethyl acetate t20 ml), and the resultant solution was dropwise added to a mixtu~e of 5 % aqueous acetic acid (10 ml) and iron powder (4 g) at 70 to 80C, followed by stirring at the same temperature for 3 hours.- The reaction mixture was ~,¢~r~

allowed to cool, diluted with water and extracted with ethyl acetate. The extract was washed with sodium bicarbonate solution, dried and concentrated to give 2-(3,4-dihydro-2(1H)-quinoxalinon 7-yl)-4,5,6,7-tetrahydro 2H-isoindole-1,3-dione (1.3 g). m.p., 208 - 209C.
In the same manner as above, the dihydroquino-xalinones (VI) as shown in Table 2 were obtained.
Table 2 (VI) -Compound X R2 R3 Physical constant No.
_ _ _ d ~ H CH3 m.p., 263.4C
e F H H m.p., 236.6C
f F CH3 H m.p., > 220C
g ~1 H H m.p., 174C

Example 3 2-(3,4-Dihydro 6-fluoro-2(lH)-quinoxalinon-7-yl)-4,5,6,7-tetrahydro-2H-isoindole-1,3-dione (0~43 g) was added to a mixture of sodium hydroxide (0.16 g), water (2.1 ml) and 30 ~ aqueous hydrogen peroxide (0.21 ml), and the resultant mixture was stirred at room temperature for 16 hours. Ether was added thereto to separate an aqueous layer, which was adjusted to pH 4 with acetic acid. The precipitated crystals were collected by filtration and washed with water to give 2-(6-fluoro-2(lH)-quinoxalinon-7-yl)-4,5,6,7-tetrahydro-2~-isoindole-1,3-dione (0.32 g) m.p., ~300C.
The tetrahydrophthAlimides can be obtained by reacting a quinoxaline of the formula:
o A~l \ ~

wherein X and A are each as defined above,with a halide of the formula:
R1_y (III) wherein R is as defined above and Y is a chlorine atom, a bromine atom or an iodine atom in a solvent in the presence of a dehydrohalogenating agent at a temperature of 0 to 50C
for a period of 0.5 to 24 hours.
In the above reaction, the halide ~III) and the dehydro-halogenating agent are used respectively in amounts of 1 to 3 equivalents per equivalent of the quinoxaline (II). Examples of the solvent are ethers (e.g. diethyl ether, diisopropyl ether, dioxane, tetrahydrofuran, ethylene glycol, dimethyl ether), acid amides (e.g.
formamide, N,N-dimethylformamide, N,N-dimethylacetamide), sulfur compounds (e.g. dimethylsulfoxide), and their mixtures. Inorganic bases (e.g. sodium hydride), organic lithium compounds (e~g. n-butyl lithiumf methyl lithium, lithium diisopropylamide), etc. may be used as the dehydro-halogenating agent.

3 ~

After completion of the reaction, the reaction mixture is subjected to an ordinary post-treatment such as extraction with an organic solvent and concentration. If desired, any conventional purification procedure, such as recrystallization or chromatography, may be employed.
Practical and presently preferred embodiments for the production of the tetrahydrophthalimides (I) are illustratively shown in the following Examples.
Example 4 10Sodium hydride (33 mg) was suspended in N,N-dimethylformamide (1.5 ml), and the resultant suspension was cooled to -30C. 2-(3,4-Dihydro-6-fluoro-2(1H)-quinoxalin-7-yl~-4,5,6,7-tetrahydro-2H-isoindole-1,3-dione (400 mg~ was added thereto at -30C, followed by stirring for 30 minutes.
1-Bromo-2-propyne (165 mg) was added thereto at -30~C, and the temperature was gradually raised to room temperature (e.g. 20 - 25~C), followed by stirring for 6 hours. The reaction mixture was admixed with water and extracted with ethyl acetate. The extract was washed with water, dried and concentrated. The residue was purified by silica gel thin layer chromatography using a mixture of ethyl acetate and hexane (1 : 2) as an eluant to give 2-[3,4-dihydro-6-fluoro-1-(2-propionyl)-2(1H)-quinoxalinon-7-yl]-4,5,6,7-tetrahydro-2H-isoindole-1,3-dione (80 mg). m.p., 205.6C.
25The tetrahydrophthalimides as shown in Table 3 were ob~ained in the same manner as above.

~ t~ `3~3 ~ o o o o ~ ~ ... o ~
tn ~ ~ t.~l ~: ' ' ' ' o~ o~
O t.~ t.
-- ~9 tJ~ ~D t.~ t~
0 ~ ~ ~
,~ tn ~ ~ 0 ~ ~ ~ ~ ~ ~ ~ rd .C ~

,.~ X ~:
U C~
VC~ ,.', o t,~ 11 ~ t,~ t,r~ t.
$
C~~, o C.) ~.~ C.) t,~l t,~ t,~ t,~ ~ ~ t,~ t,~J t,~

C~

~ C, ~
)=~ z z z æ Z Z I I æ
o~ o 11 11 11 11 t.~, t,~ t,~, t.~l 11 --\ r .¢ ~
o y y C~ y y y y o x 5 ~

O ~ t,~ t.~ t~ tJ~

O
Z;

~ , r~

o~ oo ~ . o .
r~ CO ~r ~ o co ~ a~
O ~ O
O I I I ~ ~D I ~ I
C4 ~ ~ o In O ~ ~r co In CO l` O ~ O
~ ~ ~ ~ ~ ~ f`
,~ ~
rl u~
O ~ ~ Q, ~ 0~ ~ ~ ~ R---~ ~

3~
t~ I ~ V
ll t~ ~ ~ ~ o ll ~) ll ~ ~ ~ ~ N ~`1 t~ ~`I ~ ~I ~`I

) ~ O U O

Z I Z I Z I ~ Z I Z I Z
I Z I Z ~ Z; Z I Z I Z
l l l l l l l l l l l l .
r~
O o ~ ~ ~ ~ o ~
o o ff.~,~r,~J~ 13 ~r~ t~
.,, 3 ~

~ o t, :r; ~ ~') N
N
V V ~

Z~ Z~ Z~ Z,;
~: ~ X ~C ~
V ~ V C~

X ~

O ~ ~
~Z

" ~3 G3 ~

~ 11 ~
It has been found tha-t the tetrahydrophthalimides show a high herbicidal activity against a wide variety of weeds including broad-leaved weeds, Graminacaeous weeds, Commelina-ceous weeds and Cyperaceous weeds in the agricultural plowed field by foliar or soil treatment without producing any material phytotoxicity in various agricultural crops such as corn, wheat, rice, soybean or cotton. Examples o broad-lea~ed weeds are wild buckwheat (Polygonum con~olvulus), pale smartweed (Polygonum lapathifolium), common purslane (PortuIaca oleracea), common chickweed tStellaria media), common lambsquarters (Chenopodium album3, redroot pigweed (Amaranthus retroflexus), radish (Raphanus sativus), wild mustard (Sin~is arvensis), hemp sesbania (Sesbania exaltata)~ sicklepod (Cassia obtusifolia), velvetleaf lAbutilon theophrasti), prickly sida (Sida spinosa), field pansy (Viola arvensis), catchweed bedstraw (Galium aparine) r ivyleaf morningglory (Ipomoea hederacea~, tall morningglory ~Ipomoea purpurea), henbit (Lamium amplexicaure), jimsonweed (Datura stramonium), black nightshade (Solanum niyxum), persian speedwell (Veron_ a persica), common cocklebur (Xanthium pensylvanicum~, common sunflower (Helianthus annuus), etc. Examples of Grami-naceous weeds are Japanese millet (Echinochloa frumentacea), barnyardgrass (Echinochloa crus-galli), green foxtail (Setaria viridis), large crabgrass (Diqitaria sanguinalis) annual bluegrass (Poa annua), blackgrass (Alopecurus myosuroides~, oats IAvena sativa), wild oats ~Avena fatua~, johnsongrass (Sorqhum halepense)~ etc. Examples of Commelinaceous weeds are asiatic dayflower (Commelina communis), etc. Examples of Cyperaceous weeds are yellow nutsedge (Cyperus esculentus), etc.
Further, the tetrahydrophthalimides are effecti~e in exterminating paddy field weeds including Graminaceous weeds such as barnyardgrass (Echinochloa oryzicola), broad-leaved weed such as common falsepimpernel (Lindernia procumbens), indian toothcup (Rotala indica) and waterwort (Elatine triandra), Cype-raceous weeds such as hardstem bulrush (Scirpus juncoides) and needle spikerush ~Eleocharis acicularis) and others such as monochoria (Monochoria vaqinalis) and arrowhead (Saqittaria pyqmaea), without any phytotoxicity to rice plants on flooding treatment.
Specific examples of the tetrahydrophthalimides are 2-[1-(2-propenyl)-2(1~)-quinoxalinon-7-yl]-4,5,6,7-tetrahydro-2H-isoindole-1,3 dione, 2 [3,4-dihydro-1-(2-propynyl)-2(lH)-quinoxalinon-7-yl]-4,5,6,7-tetrahydro-2H-isoindole-1,3-dione, 2-[6-fluoro-1-(2-propenyl)-2(lH)-quinoxalinon-7-yl]-4,5,6 t 7-tetrahydro-2H-isoindole-1,3-dione, 2-[3,4-dihydro-6-fluoro-1-(2-propynyl)-2(lH)-quinoxalinon-7-yl]-4,5,6,7-tetrahydro-2H-isoindole-1,3~dione, etc.

On the practical usage of the tetrahydrophthal-imides they may be applied in any preparation form such as emulsifiable concentrates, wettable powders, suspensions, ~ranules, etc. in combination with conventional solid or liquid carriers or diluents as well as surface active agents or auxiliary agents. The content of the tetrahydrophthal-imides as the active ingredient in such formulation form is usually within a range of 0.05 to 90 % by weight, pre-ferably of 0.1 to 80 % by weight. Examples of the solid carrier or diluent are fine powders or granules of kaolin clay, attapulgite clay, bentonite, terra alba, pyrophyllite, talc, diatomaceous earth, calcite, walnut powders, urea, ammonium sulfate and synthetic hydrous silicate, etc. As the liquid carrier or diluent, there may be exemplified aromatic hydrocarbons (e.g. xylene, methylnaphthalene), alcohols (e g. isopropanol, ethylene glycol, cellosolve~, ketones (e.g. acetone, cyclohexanone, isophorone), soybean oil, cotton seed oil, dimethylsulfoxide, N,N-dimethylform-amide, acetonitrile, water, etc.
The surface active agent used for emulsification, dispersion or spreading may be any of the anionic and non-ionic type of agents. Examples of the surface active agent include alkylsulfates, alkylarylsulfonates, dialkyl-sulfosuccinates, phosphates of polyoxyethylenealkylaryl ~5 ethers, polyoxyethylene alkyl e~hers, polyoxyethylene C~

alkylaryl ethers, polyoxyethylene ~olyoxypropylene block copolymer, sorbitan fatty acid esters, polyoxyethylene sorbitan fatty acid esters, etc. Examples of the auxiliary agents include ligninsulfonates, sodium alginate, polyvinyl alcohol, gum arabic, CMC (carboxymethyl cellulose3, PAP
(isopropyl acid phosphate), etc.
Practical embodiments of the herbicidal composi-tion according to the invention are illustratively shown in the following examples wherein parts are by weight. The compound number of the active ingredient corresponds to the one in Table 3.
Formulation Exam~le 1 Fifty parts of Compound No. 14, 3 parts of calcium ligninsulfonate, 2 parts of sodium laurylsulfate and 45 parts of synthetic hydrous silicate were thoroughly mixed while being powdered to form a wettable powder.
Formulation Example 2 Five parts of Compound No. 8, 14 parts of poly-oxyethylenestyrylphenyl ether, 6 parts of calcium dodecyl-benzenesu]fonate, 30 parts of xylene and 45 parts of N,N-dimethylformamide were thorou~hly mixed to form an emulsi-fiable concentrate.
Formulation Example 3 Two parts of Compound No. 5, 1 part of synthetic hydrous silicate, 2 parts of calcium ligninsulfonate, 30 parts of bentonite and 65 parts of kaolin clay were thor-oughly mixed ~hile being powdered. The mixture ~as then kneaded with water, granulated and dried to form aranules.

Formulation Example 4 Twenty-five parts of Compound No. 8 were mixed with 3 parts of polyoxyethylene sorbitan monooleate, 3 parts of carboxymethyl cellulose and 69 parts of water and pulveriæed until the particle size of the mixture became less than 5 microns to form a suspension.
The tetrahydrophthalimides thus formulated in any suitable formulation are useful for the pre-emergence or post-emergence control of undesired weeds by soil or foliar treatment as well as flood fallowing treatment. These treatments include the application to the soil surface prior to or after transplanting or incorporation into the soil. The foliar treatment may be effected by spraying the herbicidal composition containing the tetrahydrophthalimides over the top of the plants.
It may also be applied directly to the weeds if care is taken to keep the chemical off the crop foliage.
The tetrahydrophthalimides may be used together with other herbicides to improve their activity as herbicides, and in some cases, a s~nergistic effect can be expected. Further, they may be applied in combination with insecticides, acaricides, nematocides, fungicides, plant growth regulators, fertiliæers, soil improvers, etc.
Furthermore, the tetrahydrophthalimides can be used as herbicides applicable to agricultural plowed field as well as paddy field. They are also useful as herbicides to be employed for orchards, pasture land, lawns, forests, non-3. ~¢~51~3~

agricultural fields, etc.
The dosage rate of the tetrahydrophthalimides may vary depending on the prevailing weather conditions, the formulation used, the prevailing season, the mode of appli-cation, the soil involved, the crop and weed species, etc.
Generally, however r the dosage rate is from 0.02 to 100 grams, preferably from 0~05 to 50 grams, of the active in-gredient per are. The herbicidal composition formulated in the form of an emulsifiable concentrate, a wettable powder or a suspension may ordinarily be employed by diluting it with water at a volume of 1 to 10 liters per are, iE necessary, with the addition of an auxiliary agent such as a spreading agent. Examples of the spreading agent include, in addition to the surface active agents as noted above, polyoxyethylene resin acid (ester), ligninsulfon-ate, abietylenic acid salt, dinaphthylmethane~disulfonate, paraffin, etc. The composition formulated in the form of granules may normally be applied as such without dilution.
The biological data of the tetrahydrophthalimides as herbicides is illustratively shown in the following Examples wherein the phytotoxicity to crop plants and the herbicidal activity on weeds were observed visually as to the degree of germination as well as the growth inhibition and rated with an index 0, 1, 2, 3, ~ or 5, in which the nu-meral "0" indicates that no material difference is seen in comparison with the untreated plant and tlle numeral "5" which indicates complete inhibition or death of the test plants.

~ f~

The compounds shown in Table 4 below were used for comparison.
Table 4 .
No. Chemical structure ¦ Remarks A Cl Commercially ~ ~-~ available herbi-Cl~/ \ ~ ~/ \~NO2 cide; "chloro-~ Cl nitrofen"

Test Example 1 Cylindrical plastic pots (diameter, 10 cm; heignt, 10 cm) were filled with upland field soil, and the seeds of Japanese millet, tall morningglory and velvetleaf were sowed therein and covered with soil. A designated amount of the test compound formulated into an emulsifiable concentrate according to Formulation Example 2 was diluted with water, and the dilution was sprayed onto the soil surface by means of a small hand sprayer at a spray volume of 10 liters per are. The test plants were further grown in a greenhouse for 20 days, and the herbicidal activity was examined.
The results are shown in Table 5.

Table 5 Compound Dosage Herbicidal activity No. (g/are) Japanese Tall morning- Velvet-millet glory leaf ~ ~ ~ 5 / l O

Test Example 2 Cylindrical plastic pots (diameter, 10 cm; height, 10 cm) were filled with upland field soil, and the seeds of Japanese millet, radish and velvetleaf were sowed therein and cultivated in a greenhouse for 10 days. A designated amount of the test compound formulatedinto an emulsifiable concentrate according to Formulation Example 2 was diluted with water containing a spreading agent, and the dilution was sprayed over the foliage of the test plants by means of a small hand sprayer at a spray volume of 10 liters per are.

The test plants were further grown in the greenhouse for 20 days, and the herbicidal activity was examined.

The results are shown in Table 6.

? r~

Table 6 Compound Dosage ¦ Herbicidal activity No. (g/are) Japanese ¦ Radish ¦ Velvetleaf ¦
10 ~ ~ ~ ~

I~ ~.5 l l 2.5 1 0 ¦ 0 _ Test Example 3 Cylindrical plastic pots (diameter, 8 cm; height, 12 cm) were filled with paddy field soil r and the seeds of barnyardgrass (Echinochloa oryzicola3 and broad-leaved weeds (e.g. common falsepimpernel, indian toothcup, waterwort) were sowed in 1 to 2 cm depth. Water was poured therein to make a flooded condition, and rice seedlings at the 2-leaf skage were transplanted therein and grown in a greenhouse.
Six days ~at that time the weeds began to germinate) there-after, a designated amount of the test compound formulated in an emulsifiable concentrate according to Formulation Example 2 and diluted with water (5 ml) was applied to the pots by q~ 3~

perfusion. The test plants were grown for further 20 days in the greenhouse, and the herbicidal activity was examined.
The results are shown in Table 7.
Table 7 Compound Dosage Herbicidal activity No. (g/are) Rice plant Barnyard- Broad-leaved grass weed _ ¦ 20 Test Example 4 Vats (33 cm x 23 cm x 11 cm) were filled with upland field soil, and the seeds of soybean, cotton, corn, common cocklebur, tall morningglory, velvetleaf, redroot pigweed, black nightshade, barnyardgrass and green foxtail were sowed therein to 1 to 2 cm depth. A designated amount of the test compound formulated in an emulsifiable concentrate according to Formulation Example 2 was diluted with water, and the dilution was sprayed onto the soil surface by means of a small hand sprayer at a spray volume of 10 liters per are. The test plants were further grown in a greenhouse for 20 days, and the herbicidal activity was examined.
The results are shown in Table 80 3 ~ ~

~ 21 -~o~ u~ n31u~u) o a ~, ~ ~ ~ 3 ~ _ Vl~D
~/ ~ 3u~1n _ o~ ~ 3u~u~

? ~1: ~ _ u~ ~ u~ .3.3u~u~ _1 D _l _ U ~
~I C ~ .3.3.3u~ I o :~ a ~ I `3 u) 1 ~3 n I o a o I oOoo I I O

a o _ I I I I o o D O --~ I I I I O O
U~_ 'I ~ ~ u~ u~
D O t~O
E~ ~::
~ o ~ o ~ ~

~ r~ . 3 ~ ~

Test Example 5 Vats (33 cm x 23 cm x 11 cm~ were filled with upland field soil, and the seeds of wheat, catchweed bedstraw, persian speedwell, common chickweed, cornmon lambsquarters, pale smartweed, wild buckwheat and annual bluegrass were sowed therein to 1 to 2 cm depth. A designated amount of the test compound forrnulated into an emulsifiable concentrate according to Formulation Example 2 was diluted with water, and the dilution was sprayed onto the soil surface by means of a small hand sprayer at a spray volume of 10 liters per are. The test plants were further grown in 2 greenhouse for 27 days, and the herbicidal activity was examined.
The results are shown in Table 9.

C ~ ~ U~ o :~ ~ s U~ U) o G ~q 3 I `5 ~ ~ O
:~

,G -~ a ~O S o~ O

U~ U~ O
Q.3 ~:~3 U~I~ O
__00 O
cr~ Y ~` u~ _ E~ ~ C~C`J c~l ~ Ul~ $ ¢

~ r~7 ~D'~ .3 '~ ~
- 2~ -Test Example 6 Vats (33 cm x 23 cm x 11 cm) were filled with upland field soil, and the seeds of corn, wheat, sugar beet, common cocklebur, velvetleaf, black nightshade, tall morning-glory, common lambsquarters and green foxtail were sowedtherein and cultivated for 18 days in a greenhouse. A
designated amount of the test compound formulated in an emulsifiable concentrate according to Formulation Example 2 was diluted with water containing a spreading agent, and the dilution was sprayed over the foliage of the test plants by means of a small hand sprayer at a spxay volume of 5 liters per are. The test plants were further grown in the green-house for ZO days, and the herbicidal activity was examined.
At the time of application, the test plants were generally at the 1 to 4 leaf staqe and 2 to 12 cm in height, although the growth stage of the test plants varied depending on their species.
Th~ results are shown in Table 10.

c~ oo cl~
a ~, u~ _ O

e u ~ u~ o O

,v ~ u~ O O
:~ ~4C~

"' U _ _ _O
:~: a ~ 4 u~ ~, o ~O ~ 00 ~ I O ~ O O
C _ I I 0~ 0 1 00 .

l ~ ~ ~ ~_ E~l 4 ~ oo ooo O 000 0 o O

~ _ ~ ~

Claims (7)

Claims:

1. A compound of the formula:

wherein X is a hydrogen atom, a fluorine atom or a chlorine atom, R2 is a hydrogen atom or a methyl group, R3 is a hydrogen atom or a methyl group and R4 is a C1-C4 alkyl group.

2 . A compound as claimed in claim 1 wherein X is a fluorine atom.

3. A process for preparing a compound of the formula:

wherein X is a hydrogen atom, a fluorine atom or a chlorine atom, R2 is a hydrogen atom or a methyl group, R3 is a hydrogen atom or a methyl group and R4 is a C1-4 alkyl group which process comprises reacting an N-nitrophenyl-phthalimide of the formula:

wherein X is as defined above, with an amino acid ester of the formula:

wherein R2, R3 and R4 are each as defined above.

4. A process as claimed in claim 3 wherein the amino acid ester is reacted in an amount of 2.5 to 4 equivalents to one equivalent of the N-nitrophenylphthalimide.

5. A process as claimed in claim 3 wherein the reaction is conducted in a solvent.

6. A process as claimed in claim 5 wherein the solvent is dioxane, dimethylformamide or dimethylsulfoxide.

7. A process as claimed in claim 3, 4 or 5 wherein the reaction is conducted at a temperature of 50 to 200°C.