CA1042460A - Butanoic acid derivative - Google Patents

Abstract

Abstract The invention relates to 2-amino-4-(2-aminoethoxy)-butanoic acid, to a process for the manufacture of said compound, to compositions containing this compound and to the use of this compound as an abscission agent.

Description

~U4Z~6() The present invention relates to a novel substituted butanoic ~cid and to methods of preparing this material. More particularly, the present invention relates to the new substance

2-amino-4-12-aminoethoxy)-butanoic acid~ i.e, the compound of the formula I

~U2 I

and the biologically acceptable acid addition salts thereof.
The I,antipode of the compound of formula I is preferred.
The process ~r the preparation of compounds of formula I comprises a) reducing a compound of formula II

H2NCH2CH20~ f ~ . ' /C==C\ ' ~ ~
H CH_COOH

in the presence of a catalyst, or b) condensing a compound of the formula III

RlHN2CH2CH2-O--c~-cH2R2 III

: i '. ~

wherein Rl signifies a suitable nitrogen protecting group and R2 signifies chlorine, bromine or iodine, with the alkalimetal derivative of a compound of the formula IV

HF-NHR3 IV ~

COOC2H5 "' ~ " "
wherein R3 signifies a suitable nitrogen protecting group, and removing any nitrogen protecting group present in a convention-al manner, or c) resolving the racemate of a compound of formula I and isolating the L-antipode in a conventional manner, or d) converting a compound of formula I which is basic in nature into a ~ acceptable acid addition salt.
In a specific process aspect, the compound of formula I above can be prepared e.g. by the catalytic reduction o~ the known compound L-trans-2-amino-4-(2-aminoethoxy)-3-butanoic ~ ;
acid, i.e. the L-antipode of the compound of the formula:

' ~.
' ~ ' ,

- 3 -:,., ,, - ; , : ~ . : . , .. ,, .. . , :

~4Z~6~
H2~cH2cH2 \ H

C ---C
H \ ~H-COOH II

The compound of formula II above is known; its preparation is described in United States patent 3,751,459 issued August 7, 1973 in the names of Berger, Pruess and Scannell.
Conversion of the compo~d of formula II above to the desired product of formula I is accomplished by catalytic reduction. Suitable reducing systems for this purpose include hydrogen in the presnece of 5%
palladium on charcoal or hydrogen in the presence of 10% platinum on charcoal. This catalytic reduction is expediently effected in the presence of an inert solvent such as water, lower alkanols such as methanol, e~hanol and the like or mixtures of water and a lower alkanol. Temperature and pressure are not critical to this process aspect and thus the reaction may be performed at room temperature or above~ with room temperature and atmospheric pressure being the preferred conditions.
In a further process aspect the desired compound of formula I
above may be prepared by the resolution of the corresponding racemic compound, D~L-2-amino-4-(2-aminoethoxy)-butanoic acid. This racemic compound is novel and as such forms a part of the present invention. It can be prepared by condensing a compound of the formula ~HN-CH2CH2-0-CH2CH2R2 III

wherein ~ signifies a suitable nitrogen protecting group and R2 signifies chlorine, bromine or iodine with the alkali metal derivative of a compound of the formula f 3 IV
C2H5 ;~

-4--" :

. ;. , . , . . ~ . . : :.

~04246~
wherein R3 signifies a suitable nitrogen protecting group.
The alkali metal derivative of the compound of formula IV above may be prepared following conventional techniques, such as by treating said compound with an alkali metal alko~ide, for example sodium methoxide~
' or an alkali metal hydride such as sodium hydride, me condensation of the compounds of formulae III and IV yields a compound of the formula, fOOC~H5 ~MHCH2CH20CH2CH2~ - NHR3 V
~OOC H '~' wherein ~ and R3 are as described above and can be the same or different protecting groups.

Suitable nitrogen protecting groups for the purposes of the above discussed condensation reaction include acyl groups such as acetyl, sulfonyl groups such as tosyl or mesyl, the carbobenzoxy group or the phthali~ido group. It is understood that if ~ and R3 signifies a phthalimido group, the nitrogen atom does not carry a hydrogen atom.
me condensation of the compounds of formulae III and IV can be conducted without a sol~ent system or in the presence of,an inert organic solvent. Suitable solvents for this purpose include alcohols such as methanol, ethanol and the like,e~ s such as tetrahydrofuran, and dimethylformamide (DMF, with DMF being the preferred solvent. If R2 signifies chlorine, it may be expedient to add potassium iodide to the reaction mixture so that the more reactive iodide ion replaces the chloride ion. ~his reaction is effected at elevated temp,eratures ,~i,t,h a temperature ', in the range of from about 120 to about,l60 C being prefer,red., , The protecting groups, present in ,the resulting comp,ou,nd of .. ... .
, formula V are then removed to yield D,L,2-amino-4-(2-amino-ethoxy)-butanoic

-5-~. .. . . .

~ 4~2460 acid. Removal Of the protecting groups i3 accomplished following conventional techniqucs For example~ the compound of formula V wherein the protecting groups are phthalimido groups can be treated with an aqueous mineral acid, such as hydrochloric acid, to effect acid hydrolysis of the phthalimido groups. If the protecting groups present in the formula V
compound are carbobenzoxy groups, the N-protective group can be removed either by hydrogenolysis or by treatment with hydrogen brom~de in acetic acid. If the N-protective group is a tosyl group, it can be removed~
for example, by reductive cleavage with sodium in liquid ammonia.
In a still further process aspect resolution of the racemic compound, e.g~ obtainad as described above, is accomplished by first preparing the racemic diacylated product. Thus, D~L,2-amino-4_ (2-aminoethoxy)-butanoic acid is treated with a conventional acylating agent, such as ac~tic anhydride, acetyl chloride, chloroacetyl chloride, and the like. me diacylated product thus obtained is then incubated with a suitable acylase, such as hog renal acylase, which resolves the racemic compound into a mixture of D and L compounds. The L-compound of formula I above and the corresponding D-antipode can then be obtained by separating the D and L materials resulting from the acylase incubation, and removing the acyl groups by acid hydrolysis using for example aqueous hydrochlorid acid. In the final crystallization of the L-compound of formula I, this compound can be obtained as a zwitterion or as its mono- or di-acid salt, for example as its mono- or di-hydrochloride.
The novel compound of formula I above ~o~msbiologically acceptable acid addition salts with organic or inorganic acids. Suitable acids for this purpose include the hydrohalic acids such as hydrochloric acid and hydrobromic acid, other mineral acids such as sulfuric acid, phosphoric acid, nitric acid and the like~ and organic acids such as tartaric acid, citric acid, acetic acid, formic acid, maleic acid, succinic acid and the like.

... . . . . .
;~ :

.. : ' `.

~4~4~;0 Thc compound of formula I above either alone or in combination with ascorbic acid enhan~es ethylene production in fruits and therefore is useful as a plant growth regulator, especially as an abscission agent.
The role of ethylene in the ripening of fruits has been recognized in the art for over 30 years. It is known that the production of ethylene in maturing fruits increases while the fruit separates from its pedicel, mis knowledge can be utilized to demonstrate the efficacy of an abscission compound in regard to its influence on fruit to accelerate or increase the production of ethylene. Since oranges can be considered a typical fruit representative of those amenable to treatment by chemical abscission agents, the efficacy of the compound of formula I as an abscission agent ; may be illustrated with respect thereto.
The ability of the compound of formula I above to enhance ethylene production is demonstrated in the following test procedure. Whole fresh gree~ oranges and semi-ripe yellow oranges were sprayed with a 0.1% solution of the compound of formula Io The control oranges were treated with distilled water. All sprays contained 001% Aerosol~ OT (sodium dioctyl sulfosuccinate, SDS) as the wetting agent. SDS in the solutions assured in a thin ~ilm like coverage on the waxy skin of the oranges thereby producing an increased surface area for the absorption of the active mate-rial. me treated fruits were then placed in polyethylene bags, glass jars or aluminum cans and sealed. Air space of the bags or cans was sampled periodically for ethylene with gas tight syringes.
Ethylene production in the reaction vessels was determined by gas chromatography. A Hewlett Packard, Series 5750B~ Dual Fla~e Detector Research Gas Chromatograph was ~itted with lOt x 1/8" stainless ~` steel column packed with alumina (5~ H20 on neutral alumina) to determine ethylene. The instrument was operated at 45 C. The carrier gas was helium with a flow rate of 25 ml per minuteO
.
The ethylene nature of the gas measure was established by ~TRADEMARK

~',-. . ~ . .
. f: .

46(;~
r~tention time in rela~ion to pure ~thylene and it was confirmed by mercuric perchlorate [Hg~C104)~ reaction and mass spectrometry. Mercuric perchlorate absorb~ ethylene while hydrochloric acid (HCl~ raleases the absorbed gas. I'he disappearance and the reappearance of the ethylene component of the gas was noted in sampl~s treat~,d first with 1-2 ml 0.2M Hg(C104)2 and then with 1 ml 2N HCl.
The mass spectrum of pure ethylene gas was found to be comparable to the component measured as such andthe ethylene nature of the gas produced in the reaction vessels was established.
The results for this test procedure for the green oranges are reported in Table 1. These results show that in the control sample a slight amount of ethylene was produced while the rate of éthylene production was greatly enhanced in the oranges treated with the compound of formula I. me amount of ethylene produced is expressed in microliters of e~hylene/ml.

Table 1 Ethylene production by green oranges sprayed 1-1.3 gms/
orange incubated in polyethylene bags at room-temperature for 14 days.

Sam~ /ul E/ml Orange + ~istilled water 000008 Orange ~ 0 1% L-2-amino-4-(Z-aminoethoxy)-butanoic acid 0.0050 ;~

The results for this test proc~dure for the semi-ripe yellow oranges are reported in Table 2. These results shown in Table 2 are similar to those in Table 1 in that again the compound of formula I greatl~
enhanced the rate of ethylene production in the oranges.

. . . .

.:.. :
... . .

~l~4~ iO
Table 2 .
Ethylene production by yellow oranges sprayed 1-1~3 gms/
or,ange incubated in metal cans at room-tem~erature _ _ ~ul E/ml 8 da~s Orange + Distilled water 0.0009 0.0007 Orange ~ 0,1% L-2_amino_4-(2_aminoethoxy)-butanoic acid 0.0015 000044 As indicated by the above test procedures~ the compound of formula I above is useful as a ripening agent or as an abscission agent in fruit. The results discussed above show that the compound of formula I
when administered as the sole abscission agent enhances ethylene production.
In addition, it has been found that a synergistic effect is obtained from ' combinati~ns of the compound of formula I and ascorbic acid for abscission of fruit. This synergistic effect is demonstrated by repeating the same ,~
,- test procedures described above using green oranges~ spraying the oranges ^` 10 with Treatment l-distilled water Treatment 2-0.1% L,2-amino-4-(2-aminoethoxy)-butanoic acid , Treatment 3-Formulation A (ascorbic acid-58.9%~ Disodium-phosphate 4.1%~,monosodium phosphate-33.9%~ copper sul~ate -0.1% and aerosol OT-3.0~percentages in weight by weight) at 4% ascorbic acid Treatment 4-Formulation A at 4% ascorbic a~id and 0.1% L,2-amino_4_(2~am,inoethoxy)~butano,ic acid. , , , The result for this test procedure is set forth in Table 3 be-' 20 low. From these results, it can be,seen ~that a synergis,tic effect is ob-tained from the,combination of the compound of formula I and ascorbic acid for abscission of Pruit.

_g_ 2~60 Table 3 Ethylene production by green oranges sprayed 1-1.3 gms/

Sample Treatment 1 0.0008 Treatment 2 0.0050 Treatment 3 0.0032 Treatment 4 0.0225 The synergistic effect between the compound of formula I above and ascorbic acid for abscission of citrus is also demonstrated in the following field trials. These trials were conducted at Vero Beach, Florida and the applications of the test materials were made in early May. Selected branches of ~alencia orange trees were sprayed~ each treat-ment was replicated twice using branches on different trees. Treatments were applied to run-off using a one quart carbon dioxide sprayer equipped with a single 800~ Tee Jet nozzle and a pressure of 2,3 atm. The non-toxic surfactant X-77 spreader (Colloidol Products Corp., Saulsalito, California) was added to all spray solutions at 0.5%~ me composition of the sprays applied to the branches were as follows:
Treatment 1~0.4%-L,2-amino-4-~2 aminoethoxy)-butanoic acid Treatment 2-l~O~o ascor~ic acid Treatment 3-0.1%-L,2-amino-4-(2-aminoethoxy)-butanoic acid ~ O~l~o ascorbic acid Treatment 4-0.2%-L,2-amino-4-(2 aminoethoxy)-butanoic acid ~ 0.2%o ascorbic acid The only rainfall that occurred during the 14 day treatment period feel on the ninth day and amounted to 1,96 cmO me ma~imum and minimum temperatures for the test period were as follows:

-10_ : .: .: .

:
1 7~ ~ 73 ; 2 79 75 ~ 5 79 73 ; 6 77 60 '9 86 7~7~

i 12 90 75 14 90 76 .

me number of fruit was counted on each branch at time of treatment and at 7 and 14 days after treatmentO The data on the amount of fruit abscission 7 and 14 days after treatment are presented in Table 4.

Table 4 Average percent ~) F _ t abscission of Valencia oran~s Sample ~ ys Untreated 0 0 Treatment 1 Treatment 2 11 22 Treatment 3 '0 25 Treatment 4 43 57 (a) average of two replications 4~46~
Composi-tions containing th0 compound of formula I and ascorbic acid can be applied to the fruit-bearing trees in liquid or powder formu~
lations. Application may be made to the roots, trunks, limbs, leaves or fruit. For example, the abscission compositions can be dusted on the trees fro~ airplanes or applied to the base of the trees in order to be absorbed by the roots. The preferred method of application and ths most efficient is to apply the compositions to the trees rom abo~e in the form of an aqueous spray. If desired, an oily spray may be used.
In order to achieve the most efficient use of the abscission compositions~ it is preferred to apply them from about 2 to 7 days prior to harvesting of the mature fruit. It is preferred to incorporate a conventional adhesive agent into the abscission compositions of the invention as a precaution against a rainfall occurring after application and washing the abscission composition from the fruit. Examples of such adhesive agents include glue~ casein, salts of alginic acids~ cellu-lo~e ~ums and their derivatives, polyvinyl pyrrolidone, vegetable gums~
propylene glycol, invert syrup, corn syrup and the like.
These abscission compositions can contain, in addition to the compound of formula I and ascorbic acid, a water-soluble cupric salt such as cupric sulfate, cupric chloride and the like, a buffer and a surfactant. If desired, inert materials conventionally used in agriculture for applications to trees may be utilized.
In order to form the liquid spray formulations for the abscission compositions the active ingredients are dispersed in a carrier such as, for example, water or other suitable liquids. In liquid spray compositions, it is preferred to include from about 0.1% to about 0.5% by weight, based on the weight of the carrier, of a surface active agent The surface active agents may be anionic, cationic or non-ionic in character~ ~pical classes of surface active agents include alk3~lsulfonates, alklarylsulfonates, alk~lsulfates, alkylamidesulfonates~ alkylaryl polyether alcohols, fatty -12_ . ' ' ' '.' . " . .` .. ': `' ' . '.

~4;~6~) acid esters of polyhydric alcohols, ethylene oxide addition products of such esters; addition products of long chain mercaptans and ethylene oxide; sodium alkyl benæene sulfonates having from 14 to 18 carbon atoms, alkylphenylethylene oxides, e.g. paranonylphenol condensed with lO ethylene oxide l~ts or parais~octyl phenol condensed with 10 ethylene oxide units or with two ethylene oxide units or with 16 ethylene oxide units, and soaps, e.g. sodium stearate and sodium maleate~ Typical surface active agents are:
sodium salt of propylated naphthalenesulfonic acids; Aeroso~ OT manufactured by American Cyanamide Co. New York, New ~ork; X-77 Spreader manufactured by Colloidal Products Corp~, Saulsalito, California; the sodium salt of modified alcohol sulfate from coconut fatty acids; the sodium salt of sulfonated monoglyceride of coconut fatty acids; the sodium sulfonate of butylbisphenyl sorbitan sesquiolate; lauryltrimethyl ammonium chloride; octadecyltrimethyl ammonium chloride; polyethyleneglycol laurylether; Daxad~ No. 11 manufactured by Dewey and Almy Chemical Co., Cambridge, Mass. (sodium salt of polymerized aIkyl aryl sulfonic acid3; sodium oleate sulfate; sodium lauryl sulfateg Ethofats~ manufactured by Ar~our ~ Co. Chicago, ILl~ ~polyethylene esters ~;
of fatty acids or rosin acids); Ethomeens~ manufactured by Armour ~ Co., Chicago~,Ill. (polyethylene glycol derivatives of long chain alkylamines)g 20 Tritons* manufacture~d by Rohm ~ Hass Co., Philadelphia, Pa. (alkylaryl ~-polyether alcohols, sulfonates, and sulfates of the non-ionic, cationic and anionic types) and the likeO
These abscission compositions can be used to abscind a variety of fruits from trees. Typical fruits with which these compositions are efficacious include oranges, olives, apples, cherries and the like. The compositions of the invention are most efficacious in the abscission of citrus fruits, e.g., oranges, grapefruit and the like.
If, under particular application conditions, it is desirable to adjust the pH of the abscission compositions, th~s can be done following conventional techniques. For example, buffers such as disodium phosphate, *TRADEMARK

: : :

~04~9~6~
monosodi~ phosphate, sodium dibasic phosphate monohydrate and the like or mixtures of these can be incorpo~ated into -the abscission compositions to adjust the pH to the desired range.
The nature and objects of the present invention can be more fully understood by making reference to the following examples~ Unless otherwise indicated, all temperatures are given in degrees Centigrade.

Example 1 Prepa,ration of LvZ-a~ino-4-~2-a noe,tho ~ u,tan,,oic acid 10 ~a~
A solution of 125 mg of L,trans-2-amino-4-(2-aminoethoxy)-3-butenoic acid in S0 ml 90% methanol-water was reduced with H2 at 1 atmosphere and 25 in the presence of 150 mg 5% Pd on charcoal~ me catalyst was removed by filtration, the filtrate partially evaporated under reduced pressure and the concentrate applied to 5 ml Biorad~'~ AG50X4 (100-200 mesh) cation exchange resin in the H+ form. The resin was then eluted successivel~ with 10% pyridine solution and 1 M NH40H solution.
The eluates were evaporated to dryness under reduced pressure.
Thin layer chromatography of the pyridine e-luate indicated that the major ninhydrin positive component was 2-aminobutanoic acid. The ammonia eluate residue was taken up in a small volume of H20~ the pH was adjusted to 3.8 with 1 N HCl the residue concentrated to dryness and the above-identified product was crystallized from 2 ml methanol, ~pO 205-207 .

Example 2 ,` ~_=
~ydrochloride.
A solution of 125 mg. of L-trans-2-amino-4-(2-aminoethox~t3 butenoic acid in 50 ml 90% methanol-water was reduced with H2 at 1 atmosphere and 25 in the presence of 75 mg 10% platinum on charcoal.
*TRADEMARK -14-, 4~iO
The catalyst was removed by filtration, the filtrate partially evaporated under reduced pressure and the concentrate applied to 5 ml. Biora~
A~SOX4 ~100-200 mesh~ cation exchange resin in the H~ form. The resin was then eluted successively with 10% pyridine solution and lM NH40H
solution. The eluates were evaporated to dryness under reduced pressure.
Thin layer chromatography of ~he pyridine eluate indicated that the major ninhyd~in positive component was 2-aminobutanoic acid. me ammonia eluate residue were taken up in a small volume of water, the pH was adjusted to 3.8 with lN HCl, the residue concentrated to dryness and the above_ identified product was crystalli~ed from 2 ml of methanolJ m.p. 205-207 .

Example 3 Preparation of L-2-a } ~ oethoxy)-butan~oic acid h~drochloride.
A solution of 7.85 g of L,trans-2-amino-4-(2-aminoethoxy)-3-butenoic acid (40 mmoles) in 200 ml H20 was treated in a Parr apparatus at 1 atmosphere pressure and 25 for 2 hours with hydrogen in the presence of 1 g 5% Pd on charcoal. The solution was then filtered and the product was adsorbed on 70 ml AG50WX-4 cation exchange resin (100-200 mesh in the H~ form~3 The resin was eluted with 10% aqueous pyridine solution and the eluate was evaporated under reduced pressure to a 24 mg residue. The resin was then eluted with lM NH~OH, the eluate partially evaporated under reduced pressure, the concentrate adjusted to pH 5.0 with 18 ml 2N HCl and the remaining solvent evaporated under reduced pressure. The residue was taken up in hot methanol and the above-identified product crystallized after addition of ethanol m.p. 208-211 .

;

~TRADE~RK

~0~;~4~
Example 4 Preparation of D,L-2 amino-4-(2-aminoethoxy~-bltanoic .,~9~
2-Chloroethyl-2~-phthalimidoethyl ether, (37,5 mmole, 9.4 g), sodium diethyl phthalimidomalonate, (25 ~ole, 8.2 g) and potassium iodide (2.5 mmoles, 0.4 g) were dissolved in 10 ml dimethylforlllamide and the solution was maintained at 153 for 4 hours by which time titration of a small portion indicated that 99% of the malonate reagent had reacted. The product, diethyl 2-phthalimido-2-(phthalimidoethoxyethyl)-malonate could be crystallized from ethanol, m.pO 96-98 , However it was more efficient to proceed by precipitating the c~de condensation product by addition oP
4 volumes of water and triturating the precipitate 2 times with 40 ml waterO
The crude condensation product from 4/5 of the original reaction mixture was dissolved in 20 ml ethanol, 40 ml of an aqueous solution of 5 N NaOH was added and the solution was refluxed for 1 hour. The ethanol was then allowed to boil off and the cooled solution was adjusted to pH l with 6 N HCl. The aqueous phase was decanted from the oil which formed, and the oilw~s~r~luxed in 120 ml 6 N HCl for 90 minutes. After cooling~-and filtering~ the solvent was removed by evaporation under reduced pressure and the residue was dissolved in water and appl;ed to 100 ml Bio-Rad AG50X4 (50-100 mesh) cation exchange resin in the ~rform. The resin was eluted first with 100 ml 20% aqueous pyridine solution and then with 200 ml aqueous 1 N NH40H. The latter eluate was partially evaporated under reduced pressure and the pH was then adjusted to 305 with 22 meq HCl. The water was removed by evaporation under reduced pressure, the residue dissolved!,iin a small amount of methanol, and after addition of ethanol to a total volume of 50 ml7 the above-identified product crystallized during storage at 0~ miPo 175-177o l.

:`

:~V~6~) Example 5 Resolution ~ ~
A solution of D,L-2-amino-4-(2-aminoethoxy)butanoic acid, lg (5 mmole) in 5 ~l 2 N NaOH, was treate~ with 1.25 ml, 11 mmoles~
chloroac0tylchloride and the pH was maintained at 10.2 by the ad~ition of 2 N NaOH while the temperature was kept at 5 . After 45 minutes the pH was adjusted to 1.0 with 2 N ~Clo The product did not precipitate but was extracted with 5 X 10 ml ethyl ether. The combined extracts were back extracted with lO ml H20 and the organic phase evaporated at reduced pres-; 10 sure to 1.6 g syrup. The syrup was taken up in ethanol and a saturated solution of LiOH was added to an apparent pH of 7. The solvent was evaporated under reduced pressure to yield the lithi~ salt of D,L-2-chloroacetylamino-4-(2~chloroacetyl-aminoethoxy)-butanoic acid, which was crystallized from 5 ml 50% ether-ethanol, m.p. 201-203 .
solution of 642 mg of the so-obtained di-acylated product in 20 ml deionized water was treat~d with 30 mg hog renal acylase at 37 and pH 7.2 for 21 hours. The solution was then applied to a column containing 10 ml Biorad AG5~WX4 cation exchange resin l50-loo mesh in the H+ form~. -The colu~n effluent plus a 50 ml water wash was concentrated to 20 ml, the pH readjusted to 7.2 with LiOH solution, and additional 30 mg acylase added and another incubation carried out for 8 hours. The solution was then reapplied to the same column and the column effluent and watar wash were again put through the same procedure. From the final column effluent and wash, the lithium salt was made and ~-2-chloroacetylamino-4 (2-chloro-acetylaminoethoxy)butanoic acid crystallized from ethanol after removing the acylase by filtration from an aqueous ethanol suspension. After recrystallization the product showed a m.p. of 210 .
The above described resin was then eluted with 100 ml 10%
aqueous pyridine solution. The eluate was concentrated under reduced pressure and L_2-amino 4-~2-chloroacetylaminoethoxy)-butanoic acid was .: . - . . . : , :
.. . . .

~04~46iO
crystallized from ethanol water, m.p~ after recrystallization 139-141 .
The chloroacetyl groups were removed from 'both D-2~chloro-acetylamino-4-(chloroacetylaminoethoxy)butanoic acid and L_2-amino-4-~2-chloroacetylam1noethoxy)butanoic acid by refluxing 0.~ mmole of each for 2 hours in 10 ml 2N HCl~ After evaporation at reduced pressure ea'ch preparation was taken up in water and applied to a 5 ml column of Biorad AG50WX4 (50-100 mesh) cation exchange resin in the H f'~orm. After washing the columns with aqueous pyridine solution, the products were eluted with 50 ml 1 N NH40~. The solvent was partially evaporated under reduced pres-sure, the pH adjusted to 4.5 with 1 N HCl and the products crystalli~.edfrom ethanol-water. Thus, from D-2~chloroacetylamino-4-(2-chloroacetyl-aminoethoxy)-butanoic acid there was obtained D-2-amino-4-(2-aminoethox~) butanoic acid hydrochloride, m.p. 206 and from L_2-amino-4-(2-chloro-acetylaminoethoxy)-butanoic acid there was obtained L,2-amino-4-(2-aminoethoxy)-butanoic acid hydrochloride, m,p, 204-Z06 .

~.`
. .

': ' . . . . . . ' ' ' ., ' ': ~:

Claims (7)

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:

1. A process for the manufacture of a compound of formula I
and biologically acceptable acid addition salts thereof, which process comprises a) reducing a compound of formula II

II

in the presence of a catalyst, or b) condensing a compound of the formula wherein R1 signifies a suitable nitrogen protecting group and R2, signifies chlorine, bromine or iodine, with the alkali metal derivative of a compound of the formula IV

wherein R3 signifies a suitable nitrogen protecting group, and removing any nitrogen protecting group present in a conventional manner, or (c) resolving the racemate of a compound of formula I and isolating the L-antipode in a conventional manner, or (d) converting a compound of formula I which is basic in nature into a biologically acceptable acid addition salt.

2. A process according to claim 1a, wherein palladium on charcoal is used as the catalyst.

3. The compound of the formula:
I
and the biologically acceptable acid addition salts thereof.

4. The compound of claim 3 which is L-2-amino-4-(2-amino-ethoxy)-butanoic acid.

5. D,L-2-amino-4-(2-aminoethoxy)-butanoic acid.

6. A process for regulating plant growth and inducing abscission which comprises applying, to the site to be controlled, an effective quantity of a compound as claimed in claim 3.

7. A process for regulating plant growth and inducing abscission which comprises applying, to the site to be controlled, an effective amount of the compound of claim 4.