Title of Invention

NON SYMMETRICAL ETHYLENE DIAMINO HYDROXYPHENYL ACETIC ACID DERIVATIVES FOR THE TREATMENT OF IRON CHLOROSIS

Abstract The present invention consists on the synthesis of new products for the treatment of the iron chlorosis. These products may have improved properties regarding the currently known treatments. The new products are non-symmetrical ethylene diamino hidroxyphenyl acetic acid derivatives possessing only five coordination sites able to chelate metals.
Full Text New products for the treatment of the iron chlorosis
Field of the invention
This invention relates to new non-symmetrical ethylene diamino
hidroxyphenyl acetic acid derivatives. These products are useful for the
treatment of iron chlorosis.
BACKGROUND ART
Iron chlorosis is a nutritional plant disorder which results in a decrease in the
amount of chlorophyll and in the yellowing or whitening of normally green
plant tissue. It is a widespread problem in agriculture that affects the
development of many crops provoking a decrease yield.
Attempts have long been made to correct this iron deficiency by feeding the
plants with iron in assimilable form, originally in the form of ferric salts. Ferric
salts act to a certain extent by foliar penetration, but are substantially
ineffectual when used for soil treatment. It is through the roots that the
penetration of iron is at its most effective in controlling chlorosis. In this
connection, simple iron salts have been replaced by iron chelates which are
hydrosoluble complexes consisting of an iron atom attached to several points
of a single organic molecule known as chelates or co-ordinates. Some of
these products known as hexadentates, such as complexes of iron with
ethylene diamine tetracetic acid (EDTA) or with diethylene triamine pentacetic
acid (DTPA) or with N,N'-ethylene-bis-(hydroxyphenyl)glycines (EDDHA),
have been successfully used against chlorosis.
N,N'-ethylene-bis(2-hydroxyphenyl)glycine (o,o-EDDHA) is often described as
one of the most favorable compounds for complexing metals, and being most
suitable for the use as a plant nutrient or fertilizer because the complexation
affinity to iron is particularly strong. The ferric chelate of o,o-EDDHA shows a
coordination number of 6 and is widely used for agrochemical purposes as a
plant nutrient or plant fertilizer, and for the treatment of chlorosis in crop
plants.
The N,N'-ethylene-(2-hydroxyphenyl)-glycinyl-(4-hydroxyphenyl)glycine (o,p-
EDDHA) is also known in the art. Contrary to o,o-EDDHA, in the o,p-EDDHA


isomer one of the hydroxy groups is in the para- position of the benzene ring.
For this reason, the ferric chelate of o,p-EDDHA shows a coordination
number of 5 and its complexation affinity to iron is weaker than that of 0,0-
EDDHA. This compound has often being regarded as an undesired by-
product being incurred by the manufacturing process of 0,0-EDDHA.
Gomez-Gallego et al, (c.f. Chem.Eur.J. 2005, 77,5997-6005) propose a
model for explaining the reduction of the Fe(lll)-o,o-EDDHA chelate by a
ferric chelate reductase. According to it, the reduction of said chelate does
not take place on the complex in the octahedral closed form, wherein the 6
chelating points of 0,0-EDDHA are coordinated to the Fe(lll), but on a
hexacoordinate open species formed at the acid pH of the rhizosphere. As
showed in Scheme 5 of said report, one of the hydroxy groups in the ortho-
position would not be coordinated with the Fe(lll), thus generating a vacant
coordination site that would be filed with a water molecule. The complex
Fe(lll)-o,p-EDDHA, wherein one of the hydroxy groups is in the para- position,
would already be in the required open form and could be reduced directly by
the enzyme.
WO2005/095305 discloses isomeric mixtures comprising both (0,0-EDDHA)
and (o,p-EDDHA) , wherein the molar ratio of (o,p-EDDHA) to (0,0-EDDHA) is
higher than 0.8 : 1, as nutrients for agricultural crop plants and agents for
treatment of chlorosis in such plants.
SUMMARY OF THE INVENTION
The properties of the commercially available chelating agents currently used
for the treatment of iron deficiency related plant diseases (e.g. iron chlorosis),
such as those based in EDDHA and known derivatives thereof, are still not
completely satisfactory. For instance, it has been observed that current
chlorosis treatments based on 0,0-EDDHA show a delayed effect in plants.
WO2005/095305 proposes to solve this problem by employing isomeric
mixtures of 0,0-EDDHA and o,p-EDDHA, as said above. However, o,p-
EDDHA/Fe3+ shows lower stability than o,o-EDDHA/Fe3+. (Yunta et al. Journal
of Agricultural and Food Chemistry, 2003, 51, 5391-5399) so it is quite
reactive in soils.


Properties that are desirable in a compound useful for the treatment of iron
chlorosis are described in Lucena, J.J. Iron Fertilizers in Correcting Iron
Deficiencies in Plants. Chapter 5, In Iron Nutrition in Plants and Rhizospheric
Microorganism 2006, pp 103-127, Springer-Verlag Academic Publishers.
The problem to be solved by the present invention is to provide alternative
products that may be useful for the treatment of iron deficiency related plant
diseases. These products may have improved properties regarding the
currently known treatments.
The solution is based on the fact that the present inventors have identified
that by eliminating one of the carboxylic groups of EDDHA and maintaining or
modulating the hydroxyphenyl groups, the chelating affinity for polyvalent
metals, particularly for iron, is retained, while some other properties may be
improved, particularly those that make them useful for the treatment of iron
chlorosis. See working examples 1 -7 herein for a further description.
Accordingly, a first aspect of the invention relates to a compound of formula
(I):

wherein
X1 is a C6 or a C10 aromatic system having a hydroxy group in the alpha
position, being optionally substituted by up to four substituents independently
selected from the group consisting of: phospho, sulfo, halo, carboxy, acetoxy,
C1-C4 alkoxy or linear or branched C1-C4 alkyl.
X2 is a C6 or a C10 aromat ic system having a hydroxy group in the alpha
position, or a five or six membered heterocycle having in the alpha position a
heteroatom selected from the group consisting of N, O and S, optionally
comprising other N, O or S atoms in their structure, and having from 0-3
double bonds, said aromatic, or heterocyclic system being optionally


substituted by up to four substituents independently selected from the group
consisting of: phospho, sulfo, halo, carboxy, acetoxy, C1-C4 alkoxy, linear or
branched C1-C4 alkyl.
Y is (CH2)n or is a xylylene group of formula:

n is an integer selected from 2, 3 and 4,
R1, R2 are independently selected from the group consisting of H, linear or
branched C1-C4 alkyl, C6 or C10 aryl.
In a second aspect the invention relates to a process for preparing a
compound of formula (I) as defined in the first aspect of the invention and in
its corresponding embodiments, which process comprises the step of
reducing a compound of formula (II):

wherein X1, X2 and Y are as defined above, in an appropriate solvent system,
in the presence of a reducing agent.
In a third aspect the invention relates to the use of a compound of formula (I),
as defined in the first aspect of the invention and its corresponding
embodiments, as a complex forming agent for polyvalent metals.
In a fourth aspect the invention relates to a chelate of a compound of the
formula (I), as defined in the first aspect of the invention and its
corresponding embodiments, with one or more polyvalent metals.
In a fifth aspect the invention relates to an agrochemical composition
comprising a compound of formula (I), as defined in the first aspect of the
invention and its corresponding embodiments, or a polivalent metal chelate
thereof.


In a sixth aspect the invention relates to the use of a compound, as defined in
the first aspect of the invention and its corresponding embodiments, or a
polyvalent metal chelate thereof, for the preparation of a composition for
treating an iron deficiency related plant disease.
In a seventh aspect the invention relates to an intermediate of formula (II):

wherein X1, X2 and Y are as defined above, in solid form.
In a eighth aspect the invention relates to the use of the intermediate of
formula (II) as defined in the seventh aspect of the invention and its
corresponding embodiments, for the preparation of a compound of formula (I),
as defined in the first aspect of the invention and its corresponding
embodiments.
Without whishing to be bound by theory, as reported in Chem. Eur. J. 2005,
11, 5997, the effectiveness of Fe(lll)-o,o-EDDHA to relief iron chlorosis
requires the generation of a vacant coordination site. This fact explains the
high efficiency of o,p-EDDHA a compound in which one of the phenolic
groups is unable to coordinate the metal. Advantageously the new
compounds described in the invention have only five groups able to
coordinate with the metal. This point should be essential for their activity.
Furthermore, most of the derivatives of EDDHA known in the art and
employed for the treatment of iron deficiency related plant diseases are
symmetrical compounds, except for the o,p-EDDHA, which is an isomer of
EDDHA. On the contrary, all the compounds of formula (I) are non-
symmetrical compounds, since they lack one of the two carboxylic groups of
EDDHA. Therefore, the known methods for the preparation of EDDHA
derivatives were not directly applicable to the compounds of the invention.
This has forced the inventors to develop a new method of synthesis for
preparing the said compounds of formula (I).


Throughout the description and claims the word "comprise" and variations of
the word, such as "comprising", is not intended to exclude other technical
features, additives, components, or steps. The content of the application from
which priority is claimed, as well as the contents of the abstracts of the priority
application and the present application, are incorporated herein as reference.
Additional objects, advantages and features of the invention will become
apparent to those skilled in the art upon examination of the description or may
be learned by practice of the invention. The following examples are provided
by way of illustration, and it is not intended to be limiting of the present
invention.
BRIEF DESCRIPTION OF THE DRAWINGS
Figure 1 shows the SPAD index of the fourth level, represented versus the
days of treatment, for plants grown on soil treated with each of the tested
compounds and the control.
Figure 2 shows the dry weight of shoots (expressed in grams) in the soil
experiment, with the tested compounds and the control, at three sampling
times.
Figure 3 shows the iron concentration in leaves of the plants treated with the
tested compounds and the control, at three sampling times.
Definitions
By linear or branched C1-C4 alkyl, is taken to mean herein a linear or
branched alkyl group which contains up to 4 atoms of carbon. Thus it
includes, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-
butyl and tert-butyl.
By C1-C4 alkoxy it is meant herein the alkyl groups mentioned above bound
through oxygen, examples of which include methoxy, ethoxy, isopropoxy, tert-
butoxy, and the like.


The term halo, in this invention, refers to F, CI, Br, I, preferably CI.
A C6 or a C10 aromatic system or a C6 or a C10 aryl group include phenyl and
naphtyl.
DETAILED DESCRIPTION OF PARTICULAR EMBODIMENTS
As defined above, X2 in the compounds of formula (I) is a C6 or a C10 aromatic
system having a hydroxy group in the alpha position, or a five or six
membered heterocycle having in the alpha position a heteroatom selected
from the group consisting of N, O and S, optionally comprising other N, O or S
atoms in their structure, and having from 0-3 double bonds, said aromatic, or
heterocyclic system being optionally substituted by up to four substituents
independently selected from the group consisting of: phospho, sulfo, halo,
carboxy, acetoxy, C1-C4 alkoxy, linear or branched C1-C4 alkyl. Heterocycle as
meant herein includes both non-aromatic heterocycles (e.g. 2-azetidinyl, 2-
pyrrolidyl, 2-piperidinyl), and heteroaromatic rings. Preferably said
heterocycle is heteroaromatic.
Preferred compounds of formula (I) are those wherein X2 is selected from the
group consisting of 2-hydroxyphenyl, 2-hydroxy-naphthyl, 2-furyl, 2-thienyl, 2-
pyrrolyl, 2-pyridyl, 4-pyridimidinyl, 2-pyrazinyl optionally substituted by 2 or 1
substituents independently selected from the group consisting of: phospho,
sulfo, halogen, C1-C4 alkoxy, carboxy, acetoxy, linear or branched C1-C4 alkyl.
Preferred optional substituents include methyl, phenyl, phospho, sulfo,
carboxy, acetyl.
More preferred compounds of formula (I) are those wherein X1 is 2-
hydroxyphenyl or 2-hydroxynaphthyl, optionally substituted by 2 or 1
substituents independently selected from the group consisting of methyl or
methoxy. Yet more preferred are those wherein X1 is 2-hydroxyphenyl.
In the compounds of formula (I), preferably Y is (CH2)n, and more preferably n
is 2. When Y is a xylylene group as defined above, preferably both R1 and R2
are H.
In a preferred embodiment, compounds of formula (I) are those wherein Y is


(CH2)n, and more preferably n is 2, X1 is 2-hydroxyphenyl, X2 is selected from
the group consisting of 2-hydroxyphenyl, 2-hydroxynaphthyl, 2-furyl, 2-thienyl,
2-pyrrolyl, 2-pyridyl, 4-pyridmidinyl, 2-pyrazinyl, optionally substituted by 2 or
1 substituents independently selected from the group consisting of: C1-C4
alkyl, C1-C4 alkoxy, carboxy, sulfo, acetoxy .
The most particularly preferred compounds are selected from the group
consisting of:
2-(2-((2-hydroxybenzyl)amino)ethylamino)-2-(2-hydroxyphenyl)aceticacid,
2-(2-((2-hydroxy-1 -naphtyl)methylamino)ethylamino)-2-(2 -
hydroxyphenyl)acetic acid,
2-(2-((pyridin-2-yl)methylamino)ethylamino)-2-(2-hydroxyphenyl)aceticacid,
2-(2-((1H-pyrrol-2-yl)methylamino)ethylamino)-2-(2-hydroxyphenyl)acetic
acid.
Preferred methods include, but are not limited to, those described below. The
reactions are carried out in the solvents appropriate for the reagents and
materials used and suited for the transformations carried out. An expert in
organic synthesis will understand that the functional groups present in the
molecule must be consistent with the proposed transformations. This may in
some cases require modifying the order of the synthesis steps or selecting
one particular method rather than another, in order to obtain the desired
compound of the invention. Moreover, in some of the procedures described
below it may be desirable or necessary to protect the reagent functional
groups present in the compounds or intermediates of this invention with
conventional protecting groups. Various protecting groups and procedures for
introducing them and removing them are described in Greene and Wuts
(Protective Groups in Organic Synthesis, Wiley and Sons, 1999). All the
references cited herein are incorporated integrally by reference.
The compounds of formula (I) as defined above, can be prepared by a
process which comprises the step of reducing a compound of formula (II):



wherein X1, X2 and Y are as defined above, in an appropriate solvent system,
in the presence of a reducing agent.
The reaction may be carried out in different solvent systems. Suitable solvent
systems include C1-C4 alcohols such as methanol and ethanol, acetic acid,
water and mixtures thereof. Preferably the reaction is carried out in methanol.
Suitable reducing agents are hydrides and hydrogen with a metal catalyst.
Preferably, the reducing agent is selected from the group consisting of
borohydrides, such as sodium cyanoborohydride, sodium
triacetoxyborohydride, sodium borohydride. Better results are obtained when
the reducing agent used is sodium borohydride or Pd hydrogenation.
The reaction is preferably carried out at temperature ranging from 15°C to
40°C. Better results are obtained when carried out from 18°C to 25°C.
In a preferred embodiment, the process for preparing a compound of formula
(I) according to the second aspect of the invention, further previously
comprises the step of preparing said compound of formula (II) by reacting a
compound of formula (III) with a compound of formula (IV):

wherein X1, X2 and Y are as defined above, in an appropriate solvent system.
The reaction between a compound of formula (III) with a compound of formula
(IV) may be carried out in different solvent systems. Suitable solvent systems
include C1-C4 alcohols such as methanol and ethanol,-water; nitriles such as
acetonitrile; ketones such as 2-butanone; and mixtures thereof. Preferably the
reaction is carried out in methanol, ethanol, water or mixtures thereof.
In a preferred embodiment, the reaction between a compound of formula (III)
with a compound of formula (IV), and the subsequent reduction of the


compound of formula (II) obtained to prepare a compound of formula (I) is
carried out as a one pot reaction.
The best conditions to carry out the process vary according to the parameters
considered by the person skilled in the art, such as the starting materials,
temperature and similar. Such reaction conditions may be easily determined
by the person skilled in the art by routine tests, and with the teaching of the
examples included in this document.
Compounds of formula (III) are described in the literature and/or can be
prepared by methods analogous to those known in the state of the art (e.g. in
US 5,679,704, DE3329028 A1 and WO-2006045852 A1) from products
commercially available.
A compound of formula (I) as defined above may be used as a complex
forming agent for polyvalent metals. Preferably, said polyvalent metal is at
least one polyvalent metal selected from the group consisting of iron, nickel,
zinc, manganese, yterbium, gadolinium, cobalt and copper. More preferably,
said metal is iron.
A compound of the formula (I) as defined above may form chelates with one
or more polyvalent metals. Preferably, said polyvalent metal is at least one
polyvalent metal selected from the group consisting of iron, nickel, zinc,
manganese, yterbium, gadolinium, cobalt, copper, palladium, platinum and,
gold. More preferably, said metal is iron. Such iron chelates may further
contain e.g. an alkali-or alkaline earth metal, like sodium, potassium, calcium
or magnesium, particularly sodium.
Chelates according to the invention may be used as active component in
agriculturally acceptable compositions, as sole active component or in
combination with other agriculturally active components, such as plant
nutrients or plant fertilizers. Thus, agrochemical compositions according to
the invention comprise a compound of formula (I) as defined above, or a
metal chelate thereof. Said compositions may further comprise agriculturally
acceptable carriers. The composition is preferably applied in the form of a
solution or suspension by injecting into the soil.


The other agriculturally acceptable active ingredients may be additional
fertilizers, micronutrient donors or other preparations that influence plant
growth and development or plant protection products like selective herbicides
or insecticides, fungicides, bactericides, nematicides, molluscicides, or
mixtures of several of such preparations, if desired.
Agriculturally acceptable active ingredients also include other chelating
agents. Said chelating agents include ethylene diamine tetracetic acid
(EDTA), diethylene triamine pentacetic acid (DTPA), o,o-EDDHA and o,p-
EDDHA. In one embodiment, the agrochemical compositions of the invention
also comprise o,o-EDDHA.
Agriculturally acceptable carriers may be natural or regenerated mineral
substances, solvents, dispersants, wetting agents, tackifiers, thickeners or
binders. Such carriers and additives are described, for example, in WO
95/30651.
The compounds of formula (I) according to the invention are useful for
treating an iron deficiency related plant disease. Preferably, said disease is
iron chlorosis.
Preferred intermediates of formula (II) are those wherein X1 is 2-
hydroxyphenyl.
EXAMPLES
Example 1: 2-(2-((2-hydroxybenzyl)amino)ethylamino)-2-(2-
hydroxyphenyl)acetic acid
Step 1. Intermediate of formula (II) (X1= 2-hydroxyphenyl, Y=(CH2)2, X2= 2-
hydroxybenzyl)
To a solution of the 2-(2-aminoethylamino)-2-(2-hydroxyphenyl)acetic acid
hydrochloride in water at pH 7.3, was added an equimolar amount of
salicylaldehyde in ethanol. After stirring for 1 h at room temperature, the title
Schiff base was filtered and obtained as a solid in 80% yield.
1H-NMR (300 MHz, DMSO-d6, 2.5, ppm): δ = 8.54 (s, 1H, CH=N), 7.48 (d, 1H,
J= 7.5 Hz, Ar), 7.34 (t, 1H, J= 7.62 Hz, Ar), 7.30 (d, 1H, J =7.32 Hz, Ar), 7.18


(m, 1H, Ar), 6.92-6.70 (m, 4H, Ar), 4.62 (s, 1H, CH), 3.83 (m, 4H, CH2), 3.15
(m, 1H, CH2), 3.02 (m, 1H,CH2).
Step 2. 2-(2-((2-hydroxybenzyl)amino)ethylamino)-2-(2-hydroxyphenyl)acetic
acid
The hydrogenation of the of the Schiff base obtained in Step 1 in MeOH (10
% Pd/C) at room temperature yielded the title product as brown solid (80%).
1H-NMR (500 MHz, D2O, 4.8(HDO), ppm): δ = 7.20-7 (m, 4H, Ar), 6.79-6.66
(m, 4H, Ar), 4.36 (s, CH), 3.87 (s, 2H, CH2), 2.84-2.69 (m, 4H, CH2).
Example 2: 2-(2-((2-hydroxy-1 -naphtyl)methylamino)ethylamino)-2-(2-
hydroxyphenyl)acetic acid.
Step 1. Intermediate of formula (II) (X1= 2-hydroxyphenyl, Y=(CH2)2, X2=2-
hydroxy-1-naphtyl)
Following Example 1, but starting from equimolar amounts of 2-(2-
aminoethylamino)-2-(2-hydroxyphenyl)acetic acid hydrochloride and 1-
formyl-B-naphtol the the Schiff base of the title was obtained as yellow solid in
70% yield.
1H-NMR (300 MHz.DMSO, 2.5, ppm): δ = 9.11 (s, 1H, CH-N), 8.055 (d, 1H, J
= 8.35 Hz, Ar), 7.72 (d, 1H, J = 9.44 Hz, Ar), 7.63 (d, 1H, J = 7.10 Hz, Ar),
7.42 (d, 2H, J = 7.07 Hz, Ar), 7.25 (d, 1H, J = 9.44 Hz, Ar), 7.17 (d, 2H, J =
7.11 Hz, Ar), 6.75-6.67 (m, 2H, Ar), 4.43 (s, 1H), 3.86-3.78 (m, 2H, CH2), 3.2-
3.02 ( m, 1H CH2), 2.92-2.8 (m, 1H, CH2).
Step 2. 2-(2-((2-hydroxy-1-naphtyl)methylamino)ethylamino)-2-(2-
hydroxyphenyl)acetic acid
A mixture of equimolar amounts of the Schiff base obtained in Step 1,
NaBH3CN and a catalytic amount of Zn2CI in MeOH was stirred at room
temperature for 3 h. The solvent was removed by evaporation and the title
product was obtained as brown solid (85% yield).
1H-NMR (500 MHz, D2O, 4.8 (HDO), ppm): δ = 7.7-7.55 (m, 3H, Ar), 7.45-7.37
(m, 1H, Ar), 7.3-7.15 (m, 2H, Ar), 7.06 (d, 1H, J = 5.67 Hz, Ar), 6.95 (d, 1H, J
= 9.17 Hz, Ar), 6.8-7.2 (m, 2H, Ar), 5.02 (s, 1H), 4.23(s, 2H), 3.22-3.073 (m,
4H).

Example 3: 2-(2-((pyridin-2-yl)methylamino)ethylamino)-2-(2-
hydroxyphenyl)acetic acid
Step 1. Intermediate of formula (II) (X1= 2-hydroxyphenyl, Y=(CH2)2, X2-
pyridin-2-yl)
The procedure of Example 1 is followed, but starting from equimolar amounts
of 2-(2-aminoethylamino)-2-(2-hydroxyphenyl)acetic acid hydrochloride and
2-pyridinecarboxaldehyde at pH 7. After 20 h at room temperature the solvent
was removed and the title Schiff base was obtained as yellow solid in 90%
yield.
1H-NMR (300 MHz,DMSO, 2.5, ppm): δ = 8.63 (bs, 1H, J = 4.77 Hz, CH=N),
8.5-8.1 (m, 1H, Ar), 8.0-7.84 (m, 2H, Ar), 7.46 (t, 1H, Ar J = 6.58 Hz,), 7.21-
7.1 (m, 1H, Ar), 7.05-6.95 (m, 1H, Ar), 6.88-6.73 (m, 2H, Ar), 4.59 (s, 1H,
CH), 3.9 (m, 2H, CH2), 3.1-3.0 (m, 2H, CH2).
Step 2. 2-(2-((pyridin-2-yl)methylamino)ethylamino)-2-(2-hydroxyphenyl)acetic
acid
A mixture of equimolar amounts of the Schiff base obtained in Step 1 and
NaBH4 in MeOH was stirred at room temperature for 20 h. The solvent was
removed by evaporation and the title product was obtained as white solid
(95% yield).
1H-NMR (300 MHz, D2O, 4.8 (HDO) ppm): δ = 8.4-8.36 (m, 1H, Ar), 7.82 (td, 1
H, J, = 7.65 Hz, J2 = 1.38 Hz, Ar), 7.77-7.72 (m, 2H, Ar), 7.36-7.25 (m, 2H,
Ar), 7.2-7.0 (m, 1H, Ar), 6.74-6.65 (m, 1H, Ar), 4.38 (s, CH), 3.76 (s, 2H, CH2),
2.78-2.6 (m, 4H, CH2).
Example 4: 2-(2-((1H-pyrrol-2-yl)methylamino)ethylamino)-2-(2-
hydroxyphenyl)acetic acid
Step 1. Intermediate of formula (II) (X1= 2-hydroxyphenyl, Y=(CH2)2, X2=1H-
pyrrol-2-yl)
Following the procedure of Example 1, but starting from equimolar amounts of
2-(2-aminoethylamino)-2-(2-hydroxyphenyl)acetic acid hydrochloride and
pyrrole-2-carboxaldehyde, the title Schiff base was obtained after stirring at
room temperature for 20 h as orange solid in 90% yield.


1H-NMR (300 MHz.DMSO, 2.5, ppm): δ = 8.09 (s, 1H, CH=N), 7.35-7.20 (m,
1H, Ar), 7.0-6.95 (m, 1H, Ar), 6.87 (s, 1H, Ar), 6.75-6.65 (m, 1H, Ar), 6.5-6.4
(m, 1H, Ar), 6.3-6.2 (m, 1H, Ar), 6.115-6.05 (m, 1H, Ar), 4.11 (s, 1H , CH),
3.65-3.5 (m, 2H, CH2), 2.9-2.6 (m, 2H, CH2).
Step 2. 2-(2-((1H-pyrrol-2-yl)methylamino)ethylamino)-2-(2-
hydroxyphenyl)acetic acid
A mixture of equimolar amounts of the Schiff base obtained in Step 1 and
NaBH4 in MeOH was stirred at room temperature for 20 h. The solvent was
removed by evaporation and the title product was obtained as orange solid
(94% yield).
1H-NMR (500 MHz, D2O, 4.8(HDO), ppm): δ = 7.2-7.1. (m, 2H, Ar), 6.80-6.69
(m, 3H, Ar), 6.15-6.25 (m, 2H, Ar), 4.44 (s, 1H), 3.70 (s, 2H, CH2), 2.85-2.6
(m,4H,CH2).
Example 5: 2-(2-((imidazol-4(5)-yl)methylamino)ethylamino)-2-(2-
hydroxyphenyl)acetic acid
Step 1. Intermediate of formula (II) (X1= 2-hydroxyphenyl, V=(CH2J2,
X2=imidazol-4(5)-yl)
To a solution of the 2-(2-aminoethylamino)-2-(2-hydroxyphenyl)acetic acid
hydrochloride in water at pH 7.2, was added an equimolar amount of 4(5)-
formylimidazole in methanol. After stirring for 24 h at room temperature, the
title Schiff base was filtered and obtained as a solid in quantitative yield.
1H-NMR (300 MHz, CD3OD, 3.31 ppm): δ = 8.21 (broad s, 1H, CH=N), 7.76 (s,
1H, CH=N), 7.49 (s, 1H, CH=N), 7.23 (dt, 1H, J, = 7.56 Hz, J2 = 1.35 Hz, Ar),
7.10 (td, 1H, J, = 1.38 Hz, J2 = 7.56 Hz, Ar), 6.77 (m, 2H, Ar), 5.74 (1H, NH),
4.44 (s, 1H, CH), 3.72-3.70 (m, 2H, CH2), 3.08-3.0 (m, 1H, CH2), 2.95-2.34
(m, 1H, CH2).
Step 2. 2-(2-((imidazol-4(5)-yl)methylamino)ethylamino)-2-(2-
hydroxyphenyl)acetic acid
The hydrogenation of the Schiff base obtained in Step 1 in MeOH (10 %
Pd/C) at room temperature yielded the title product as a solid (35%).
1H-NMR (500 MHz, D2O, 4.8 (HDO) ppm): δ = 7.55 (s, 1H, C=N), 7.06-7.0.3
(m, 2H, Ar), 6.88 (s, 1H, C=N), 6.68-6.64 (m, 2H, Ar), 4.33 (s, 1H, CH), 3.59
(s, 2H, CH2), 2.76-2.56 (m, 4H, CH2).

Example 6: 2-(2-((1 H-imidazol-2-yl)methylamino)ethylamino)-2-(2-
hydroxyphenyl)acetic acid
Step 1. Intermediate of formula (II) (X1= 2-hydroxyphenyl, Y=(CH2)2, X2=1H-
imidazol-2-yl)
To a solution of the 2-(2-aminoethylamino)-2-(2-hydroxyphenyl)acetic acid
hydrochloride in water at pH 7.2, was added an equimolar amount of 2-
formylimidazole in methanol. After stirring for 24 h at room temperature, the
title Schiff base was filtered and obtained as a solid in quantitative yield.
1H-RMN (500 MHz, CD3OD, 3.31 ppm) δ = 8.24 (broad s, 1H, CH=N), 7.18 (s,
2H, CH=N), 7.10-6.97 (m, 2H, Ar), 6.79-6.73 (m, 2H, Ar), 5.72 (broad s, 1H,
NH), 4.36 (s, 1H, CH), 3.79-3.75 (m, 2H, CH2), 3.03-2.94 (m, 1H, CH2), 2.89-
2.84 (m, 1H,CH2).
Step 2. 2-(2-((1H-imidazol-2-yl)methylamino)ethylamino)-2-(2-
hydroxyphenyl)acetic acid
The hydrogenation of the of the Schiff base obtained in Step 1 in MeOH (10
% Pd/C) at room temperature yielded the title product as a solid (34%).
1H-RMN (500 MHz, D2O, 4.8 (HDO) ppm) δ = 7.55 (s, 1H, C=N), 7.06-7.03 (m,
2H, Ar), 6.88 (s, 1H, C=N), 6.68-6.64 (m, 2H, Ar), 4.33 (s, 1H, CH), 3.59 (s,
2H, CH2), 2.76-2.56 (m, 4H, CH2).
Example 7: 2-(2-((piperidin-2-yl)methylamino)ethylamino)-2-(2-
hydroxyphenyl)acetic acid
Step 1. Intermediate of formula (II) (X1= 2-hydroxyphenyl, Y=(CH2)2, X2-
piperidin-2-yl)
To a solution of the 2-(2-aminoethylamino)-2-(2-hydroxyphenyl)acetic acid
hydrochloride in water at pH 7.2, was added an equimolar amount of 2-formyl-
N-terbutoxycarbonyl-piperidine in methanol. After stirring for 24 h at room
temperature, the title Schiff base was filtered and obtained as a solid in
quantitative yield.
1H-NMR (300 MHz, DMSO-d6, 2.5, ppm): δ = 7.57 (s, 1H, C=N), 7.28-7.26 (m,
2H, Ar), 7.0- 6.96 (m, 2H, Ar), 4.5 (s, 1H, CH), 4.14-4.05 (m, 1H, CH), 3.3-
2.80 (m, 6H, CH2), 1.49-1.36 (m, 6H, CH2), 1.36 (s, 9H, CH3).

Step 2. 2-(2-((piperidin-2-yl)methylamino)ethylamino)-2-(2-
hydroxyphenyl)acetic acid
The hydrogenation of the of the Schiff base obtained in Step 1 in MeOH (10
% Pd/C) at room temperature, followed by removal of the terbutoxycarbonyl
(BOC) group with 1 mL of 10% H2SO4 in 10 mL dioxane, 24 h at room
temperature, yielded the title product as a solid (60%).
1H-RMN (500 MHz, D2O, 4.8 (HDO) ppm): δ = 7.21-7.16 (m, 2H, Ar), 6.72-
6.67 (m, 2H, Ar), 4.35 (s,1H, CH), 3.56-3.51 (m, 1H, CH), 3.1-2.52 (m, 8H,
CH2), 1.49-1.45 (m, 2H, CH2), 1.13-1.03 (m, 4H, CH2).
Example 8: 2-(2-((pyrrolidin-2-yl)methylamino)ethylamino)-2-(2-
hydroxyphenyl)acetic acid
Step 1. Intermediate of formula (II) (X1= 2-hydroxyphenyl, Y=(CH2)2, X2=
pyrrolidin-2-yl)
To a solution of the 2-(2-aminoethylamino)-2-(2-hydroxyphenyl)acetic acid
hydrochloride in water at pH 7.2, was added an equimolar amount of 2-formyl-
N-terbutoxycarbonyl-pyrrolidine in methanol. After stirring for 24 h at room
temperature, the title Schiff base was filtered and obtained as a solid in
quantitative yield.
1H-RMN (500 MHz, DMSO-d6, 2.5, ppm): δ = 7.57 (broad s, 1H, C=N), 7.27
(d, 1H, J = 7.35 Hz, Ar), 7.01 - 6.91 (m, 1H, Ar), 6.66- 6.59 (m, 2H, Ar), 4.6 (m,
1H, CH), 3.92 (s, 1H, CH), 2.71-2.6 (m, 1H, CH2), 2.59-2.45 (m, 1H, CH2),
1.99-1.75 (m, 4H, CH2), 1.38-1.37 (m, 2H, CH2), 1.37 (s, 9H, CH3).
Step 2. 2-(2-((pyrrolidin-2-yl)methylamino) ethylamino) -2-{2-
hydroxyphenyl)acetic acid
The hydrogenation of the of the Schiff base obtained in Step 1 in MeOH (10
% Pd/C) at room temperature, followed by removal of the BOC group with 1
mL of 10% H2SO4 in 10 mL dioxane, 24 h at room temperature, yielded the
title product as a solid (50%).
1H-RMN (500 MHz, D2O, 4.8 (HDO) ppm): δ = 7.31-7.26 (m, 2H, Ar), 6.91-
6.87 (m, 2H, Ar), 5.1 (s, 1H, CH), 3.9-3.83 (m, 1H, CH), 3.44-3.20 (m, 8 H,
CH2), 1.96-1.65 (m, 4 H, CH2).

Example 9: 2-(2-((2-hydroxybenzyl)amino)ethylamino)-2-(2-hydroxy-4-
methylphenyl)acetic acid
Step 1. Intermediate of formula (II) (X1= 2-hydroxy-4-methylphenyl, Y=(CH2)2,
X2= 2-hydroxybenzyl)
To a solution of the 2-(2-aminoethylamino)-2-(2-hydroxy-4-
methylphenyl)acetic acid hydrochloride in water at pH 7.2, was added an
equimolar amount of salicylaldehyde in ethanol. After stirring for 1 h at room
temperature, the title Schiff base was filtered and obtained as yellow solid in
65% yield.
1H-NMR (300 MHz, DMSO-d6, 2.5, ppm): δ = 8.54 (s, 1H, CH=N), 7.45 (d, 1H,
J = 7.78 Hz, Ar), 7.33 (td, 1H, J, = 1.63 Hz, J2 = 8.2 Hz, Ar), 7.08 (d, 1H, J
=7.7 Hz, Ar), 6.9 (t, 2H J = 7.27 Hz Ar), 6.61-6.58 (m, 2H, Ar), 4.56 (s, 1H,
CH), 3.85-3.81 (m, 2H, CH2), 3.17-3.09 (m, 1H, CH2), 3.09-2.95 (m, 1H, CH2),
2.18 (s, 3H,CH3).
Step 2. 2-(2-((2-hydroxybenzyl)amino)ethylamino)-2-(2-hydroxy-4-
methylphenyl)acetic acid
The hydrogenation of the of the Schiff base obtained in Step 1 in MeOH (10
% Pd/C) at room temperature yielded the title product as brown solid (75%).
1H-NMR (500 MHz, D2O, 4.8 (HDO), ppm): δ = 7.22-7.1 (m, 3H, Ar), 6.72-6.64
(m, 4H, Ar), 4.37 (s, 1H, CH), 3.92 (s, 2H, CH2), 2.59-2.81 (m, 4H, CH2), 2.23
(s, 3H, CH3).
Example 10: 2-(2-((2-hydroxybenzyl)amlno)ethylamino)-2-(2-hydroxy-5-
methylphenyl)acetic acid
Step 1. Intermediate of formula (II) (X1= 2-hydroxy-5-methylphenyl, Y=(CH2)2,
X2= 2-hydroxybenzyl)
To a solution of the 2-(2-aminoethylarnino)-2-(2-hydroxy-5-
methylphenyl)acetic acid hydrochloride in water at pH 7.2, was added an
equimolar amount of salicylaldehyde in ethanol. After stirring for 1 h at room
temperature, the title Schiff base was filtered and obtained as yellow solid in
52% yield.


1H-NMR (300 MHz, DMSO-d6, 2.5, ppm): δ = 8.55 (s, 1H, C=N), 7.45 (d, 1H, J
= 7.6 Hz, Ar), 7.32 (t, 1H, J = 8.81 Hz, Ar), 7.02 (s, 1H, Ar), 6.90 (t, 3H, J =
7.56 Hz, Ar), 6.68 (d, 1H, J = 8.13, Ar), 4.52 (s, 1H, CH), 3.85-3.80 (m, 2H,
CH2), 3.2.-3.12 (m, 1H, CH2), 3.01-2.94 (s, 1H, CH2), 2.17 (s, 3H, CH3).
Step 2. 2-(2-((2-hydroxybenzyl)amino)ethylamino)-2-(2-hydroxy-5-
methylphenyl)acetic acid
The hydrogenation of the of the Schiff base obtained in Step 1 in MeOH (10
% Pd/C) at room temperature yielded the title product as brown solid (70%).
1H-NMR (500 MHz, D2O, 4.8 (HDO), ppm): δ = 7.18 (t, 1H, J = 6.14 Hz, Ar),
7.2-7.15 (m, 2H, Ar), 6.92-6.89 (s, 1H, Ar), 6.89-6.68 (m, 3H, Ar), 5.15 (s, 1H,
CH), 4.16 (s, 2H, CH2), 3.36-3.19 (m, 4H, CH2), 2.19 (s, 3H, CH3).
Example 11: Preparation of ferric chelates
The general procedure used for preparing the ferric chelates of the
invention is the following:
To a solution of the ligand of formula (I) in NaOH (1:3 ligand:NaOH molar
ratio), is added a solution of the equimolar amount of FeCI3-6H2O in water.
During the addition, the pH of the solution should be maintained between 6.0-
8.0 by addition of NaOH or HCI, and finally adjusted to 7. The final solution is
filtered through 0.45 urn cellulose membranes before use.
Example 12: Determination of Titrimetric purity of the chelating agent
Photometric titration
Chelating agent solution was prepared by dissolving an amount of chelating
agent in the necessary amount of NaOH solution. Then pH is adjusted to 6 by
the addition of MES biological buffer [2-(N-morpholino) ethanesulfonic acid]
and maintaining at this pH with NaOH solution during the titration. Ionic
strength is fixed at 0.1 M with NaCI and upper atmosphere was N2free of C02
The test solution was placed in a thermostated jacketed reaction vessel
(i.e.100 ml or 150 ml capacity) with an airtight cap fitted with gas inlet and
outlet tubes, the combined pH glass electrode, the photometric detector and
two piston burettes, tip extending below the surface of the solution, and a


magnetic stirrer. The photometric titration consisted of the addition of a Fe(lll)
standard solution, previously standardized by Atomic Absorption
Spectroscopy, to the chelating agent until the absorbance at 480 nm presents
no changes. End-point titration could be calculated for two linear segments'
intersection and also using smoothed second derivative method.
Potentiometric titration
The chelating agent purities could also be determined by potentiometric
titrations with a Cu2+ ion selective electrode in the same conditions as before.
The chelating agent solution is titrated with Cu(ll) solution using selective
Cu(ll) electrode and reference electrode, Cu2+ free cation is measured with
the selective electrode. The end-point of the potentiometric titrations could be
determined by Gran equation method or using the first derivative method.
Previously, the Cu(ll) solution used as titrant solution is standardize with
EDTA-Na2 solution and the selective electrode slope is determined by titration
of NaCI solution fixed at pH=6 with Cu(ll) as titrant solution.
Example 13: Determination of agrochemical activity
Efficacy of Fe chelates to provide Fe to soybean plants in hydroponics.
Soybean seeds (Glycine max L. cv. Stine 0480) were germinated at 30
°C and 60% RH on paper moistened with 1 M CaSO4 in dark for 2 days.
Afterwards, seedlings were placed in 10 L containers (50 seedlings per
container) filled with a 1/5 diluted EDTA buffered nutrient solution
(macronutrients (mM)- 1.0 Ca(NO3)2j 0.9 KNO3, 0.3 MgSO4> 0.1 KH2PO4;
cationic micronutrients (uM)- 5.0 EDTA/Fe3+, 2.5 MnSO4, 1.0 CuSO4, 10
ZnSO4, 1.0 CoSO4, 1.0 NiCI2, 11.5.5 Na2EDTA; anionic micronutrients (μM)-
35 NaCI, 10 H3B03, 0.05 Na2Mo04; 0.1 mM HEPES) for 6 days. On the 7th
day, in order to induce Fe chlorosis, seedlings were transferred to 12 L
polypropylene buckets containing aerated full strength EDTA buffered
nutrient solution but without Fe3+-chelate. Plants were grown under these
conditions until clear symptoms of Fe deficiency were observed (7 days) and
then plants were placed in 2 L pots (6 plants per pot) covered with black
plastic to avoid light exposure. The effect of different Fe chelates and doses


were compared as Fe sources. Chelates used in the treatments were 0,0-
EDDHA/Fe3+, o,p-EDDHA/Fe3\ EDTA/Fe3+ and Example 1/Fe3+. The last one
is the Fe chelate of the compound of the example 1: 2-(2-((2-
hydroxybenzyl)amino)ethylamino)-2-(2-hydroxyphenyl)acetic acid (DCHA).
Nutrient solution contained macronutrients and anionic imicronutrients as for
the seedling period and the following cationic micronutrients composition:
OiM) 1.0 MnSO4, 0.5 CuSO4, 0.5 ZnSO4l 0.1 NiCI2 and 0.1 CoSO4. Also, 1g-L"
1 of CaC03 was added to the nutrient solution to buffer pH at 7.5 and to
simulate conditions of a calcareous soil. Plants were grown for 21 days in this
nutrient solution in a growth chamber provided with fluorescent and sodium
vapour lamps with a 16 h/30 °C and 50% humidity day and 8 h/25 °C and
70% humidity night regime. Water was added every 2 days and the nutrient
solution was renewed every 7 days. Treatments were replicated four times in
a completely randomised design. Plants were harvested after 7, 14 and 21
days.
During the experiment, SPAD readings with a chlorophyll-meter (Minolta
SPAD-502) were taken for all leaf stages (average of two or three readings
per stage) every second day. Only values measured for the youngest fully
open leaves (the 2nd stage at the 2nd day, the third at the 10th day and the
fourth at the 20th day) are here presented (Table 1)
Table 1. Effects of Fe chelates treatments on the SPAD index measured.



Different letters in the columns denote significant differences (α=0.05) among
treatments according to the Duncan Test
The chlorophyll and the recovery of plants after the treatments application
were estimated by the SPAD index. Table 1 shows the time course of this
parameter. Two days after the treatment application, plants treated with
10 uM o,p-EDDHA/Fe3+ showed the highest SPAD index values but it only
showed significant differences with 5 uM o,o-EDDHA/Fe3+, 5 uM EDTA/Fe3+
and -Fe treatments. Ten days after, plants treated with 5 uM and 10 uM
Example 1/Fe3+ and 10uM o,p-EDDHA/Fe3+ had significantly regreened in
relation to 5 uM o,o-EDDHA/Fe3+, 5 uM and 10uM EDTA/Fe3+and -Fe
treatments. At the end of the experiment (20 days after the treatments
application), regardless of the doses, plants treated with Example 1, o,o-
EDDHA and o,p-EDDHA Fe chelates (T1, T2, T3, T4, T5 and T6) had
completely regreened showing significant SPAD index values concerning 5
μM and 10 uM doses of EDTA/Fe3+ and -Fe treatments.
Considering the low doses applied and the trend observed, we can conclude
that the product obtained in Example 1 presents a fast action to correct iron
chlorosis, similar to o,p-EDDHA, but higher than o,o-EDDHA.
Root and shoot were separated and washed using Tween 80 (Merck) and HCI
solution and fresh and dry (after oven dry procedure) weights were
determined. Samples were ground and after dry digestion in a muffle furnace
(480 °C), ashes are dissolved in HCI. Fe, Mn, Cu and Zn were analysed by
atomic absorption spectrometry.
In Table 2 the Fe content in the plants in each sampling time for the
treatments with the lower Fe application is presented. It can be observed that


the novel compound Example 1/Fe3+ is able to provide significantly higher
amounts of iron and faster in this experimental conditions than the other
treatments, even more than o,p-EDDHA in the third sampling time. However,
when a large doses of Fe is used (10 uM, table 3) differences are only
significant respect the treatment with EDTA/Fe3+. It can be concluded that
Example 1/Fe3+ can be used in lower concentration than other chelates to
correct the iron chlorosis.
Table 2 Fe content (ug Fe per plant) in plants treated with the low doses of
chelates

Different letters in the columns denote significant differences (a =0.05) among
treatments according to the Duncan Test.
Table 3 Fe content (ug Fe per plant) in plants treated with the high doses of
chelates


Different letters in the columns denote significant differences (a =0,.05)
among treatments according to the Duncan Test.
Efficacy of Fe chelates to provide Fe to soybean plants in soil conditions
Soybean seeds (Glycine max L. cv. Stine 0480) were germinated at 30 °C
and 60% RH on paper moistened with 1 M CaSO4 in dark for 2 days.
Afterwards, seedlings were placed in 10 L containers (50 seedlings per
container) filled with a 1/5 diluted EDTA buffered nutrient solution
(macronutrients (mM)- 1.0 Ca(NO3)2, 0.9 KNO3, 0.3 MgSO4, 0.1 KH2PO4;
cationic micronutrients (μM)- 5.0 EDTA/Fe3+, 2.5 MnSO4, 1.0 CuSO4, 10
ZnSO4, 1.0 CoSO4> 1.0 NiCI2, '115.5 Na2EDTA; anionic micronutrients (uM)-
35 NaCI, 10 H3BO3, 0.05 Na2MoO4; 0.1 mM HEPES) for 4 days. Then, in
order to induce Fe chlorosis, nutrient solution without iron was used for two
more days and then plants were transplanted in 1 L pots (3 plants per pot)
containing 700 g of a calcareous soil (380 mg-Kg-1 calcium carbonate, 89 g
Kg-1 CaCO 3 active, pH 7.70) and 300 g of lime sand covered with black
plastic to avoid light exposure. The effect of different Fe chelates were
compared as Fe sources: o,o-EDDHA/Fe3+, o,p-EDDHA/Fe3+, EDTA/Fe3+ and
Example 1/Fe3+. The last one is the Fe chelate of the compound of the
example 1: 2-(2-((2-hydroxybenzyl)amino)ethylamino)-2-(2-


hydroxyphenyl)acetic acid. Plants were grown for 21 days in this soil
conditions in a growth chamber provided with fluorescent and sodium vapour
lamps with a 16 h/30 °C and 50% humidity day and 8 h/25 °C and 70%
humidity night regime. Treatments were replicated five times in a completely
randomised design. Single plants were harvested after 2, 7 and 21 days.
During the experiment, SPAD readings with a chlorophyll-meter (Minolta
SPAD-502) were taken for all leaf stages (average of two or three readings
per stage) every second day. Values measured for the 2nd stage at the 2nd
day, the third at the 12th day and the fourth and fifth at the 22th day) are here
presented (Table 4).
Table 4. Effects of Fe chelates treatments on the SPAD index measured in
the soil experiment

Different letters in the columns denote significant differences (a=0.05) among
treatments according to the Duncan Test.
All chelate treatments present higher SPAD indexes than control, as shown in
Figure 1. This and the visual symptoms indicate that the recovery from
chlorosis using these chelates was complete. Two days after the treatment
application, plants treated with o,p-EDDHA/Fe3+ and Example 1/Fe3+
presented the better recovery, due to the fast action of these compounds, and


after that it is the treatment with the o,o-EDDHA/Fe3+ the one which gives the
highest values but similar to Example 1/Fe3+.
In each sampling time shoots were separated and washed using Tween 80
(Merck) and HCI solution and fresh and dry (after oven dry procedure)
weights were determined. Samples were ground and after dry digestion in a
muffle furnace (480 °C), ashes were dissolved in HCI. Fe, Mn, Cu and Zn
were analysed by atomic absorption spectrometry.
In Figure 2 the dry weight obtained for the shoots is presented. Again the
Example 1/Fe3+ revealed as an efficient Fe chlorosis corrector. Also in Figure
3 the iron concentration in leaves is shown for the three sampling times. The
three iron chelates considerably increase the Fe concentration with respect to
the control.
From this experiment, with only one treatment application, we can conclude
that the product obtained in Example 1 is efficient to solve iron chlorosis in
highly calcareous conditions. Its efficacy is related with its fast action
mechanism.


CLAIMS
1. A compound of formula (I):

wherein
X1 is a C6 or a C10 aromatic system having a hydroxy group in the alpha
position, being optionally substituted by up to four substituents independently
selected from the group consisting of: phospho, sulfo, halo, carboxy, acetoxy,
C1-C4 alkoxy, linear or branched C1-C4 alkyl.
X2 is a C6 or a C10 aromatic system having a hydroxy group in the alpha
position, or a five or six membered heterocycle having in the alpha position a
heteroatom selected from the group consisting of N, O and S, optionally
comprising other N, O or S atoms in their structure, and having from 0-3
double bonds, said aromatic, or heterocyclic system being optionally
substituted by up to four substituents independently selected from the group
consisting of: phospho, sulfo, halo, carboxy, acetoxy, C1-C4 alkoxy, linear or
branched C1-C4 alkyl.
Y is (CH2)n or is a xylylene group of formula:

n is an integer selected from 2, 3 and 4,
R1, R2 are independently selected from the group consisting of H, linear or
branched C1-C4 alkyl, C6 or C10 aryl.
2. The compound according to claim 1, wherein X2 is selected from the group
consisting of 2-hydroxyphenyl, 2-hydroxy-naphthyl, 2-furyl, 2-thienyl, 2-
pyrrolyl, 2-pyridyl, 4-pyridimidinyl, 2-pyrazinyl optionally substituted by 2 or 1
substituents independently selected from the group consisting of: phospho,


sulfo, halogen, C1-C4 alcoxy carboxy, acetoxy, linear or branched C1-C4 alkyl.
3. The compound according to claim 2, wherein X1 is 2-hydroxyphenyl or 2-
hydroxynaphthyl, optionally substituted by 1 or 2 substituents independently
selected from the group consisting of methyl or methoxy.
4. The compound according to claim 3, wherein X1 is 2-hydroxyphenyl.
5. The compound according to any one of claims 1 to 4, wherein Y is (CH2)n
6. The compound according to claim 5, wherein n is 2.
7. A process for preparing a compound of formula (I) as defined in claims 1 to
6, which process comprises the step of reducing a compound of formula (II):

wherein X1, X2 and Y are as defined above, in an appropriate solvent system,
in the presence of a reducing agent.
8. The process according to claim 7, further previously comprising the step of
preparing said compound of formula (II) by reacting a compound of formula
(III) with a compound of formula (IV):

wherein X1, X2 and Y are as defined above, in an appropriate solvent system.
9. Use of a compound of formula (I) as defined in claims 1 to 6 as a complex
forming agent for polyvalent metals.


10. A chelate of a compound of the formula (I) as defined in any of claims 1 to
6 with one or more polyvalent metals.
11. A chelate according to claim 10, wherein said polyvalent metal is at least
one polyvalent metal from the group consisting of iron, nickel, zinc,
manganese, yterbium, gadolinium, cobalt, copper, palladium, platinum and,
gold.
12. The chelate according to claim 11, wherein said polyvalent metal is iron.
13. An agrochemical composition comprising a compound of formula (I) as
defined in any of claims 1 to 6 or a polyvalent metal chelate thereof.
14. The agrochemical composition according to claim 13, further comprising a
chelating agent selected from the group consisting of ethylene diamine
tetracetic acid (EDTA), diethylene triamine pentacetic acid (DTPA), N,N'-
ethylene-bis(2-hydroxyphenyl)glycine (o,o-EDDHA) and N,N'-ethylene-(2-
hydroxyphenyl)-glycinyl-(4-hydroxyphenyl)glycine (o,p-EDDHA).
15. Use of a compound as defined in claims 1 to 6 or a polyvalent metal
chelate thereof for the preparation of a composition for treating an iron
deficiency related plant disease.
16. The use according to claim 15, wherein said disease is iron chlorosis.
17. An intermediate of formula (II):
>
wherein X1, X2 and Y are as defined above, in solid form.
18. The intermediate of formula (II) according to claim 17, wherein X1 is 2-
hydroxyphenyl.


19. The intermediate of formula (II) according to claim 18, wherein Y is (CH2)2-
20. Use of the intermediate of formula (II) as defined in any of claims 17 to 19,
for the preparation of a compound of formula (I), as defined in any of claims 1
to 6.

The present invention consists on the synthesis of new products for the treatment of the iron chlorosis. These products may have improved properties regarding the currently known treatments. The new products are non-symmetrical ethylene diamino hidroxyphenyl acetic acid derivatives possessing only five coordination sites able to chelate metals.

Documents:

2067-KOLNP-2009-(01-01-2015)-ABSTRACT.pdf

2067-KOLNP-2009-(01-01-2015)-ANNEXURE TO FORM 3.pdf

2067-KOLNP-2009-(01-01-2015)-CLAIMS.pdf

2067-KOLNP-2009-(01-01-2015)-CORRESPONDENCE.pdf

2067-KOLNP-2009-(01-01-2015)-DESCRIPTION (COMPLETE).pdf

2067-KOLNP-2009-(01-01-2015)-FORM-1.pdf

2067-KOLNP-2009-(01-01-2015)-FORM-2.pdf

2067-KOLNP-2009-(01-01-2015)-FORM-3.pdf

2067-KOLNP-2009-(01-01-2015)-FORM-5.pdf

2067-KOLNP-2009-(01-01-2015)-OTHERS.pdf

2067-KOLNP-2009-(01-01-2015)-PA.pdf

2067-KOLNP-2009-(02-07-2014)-ANNEXURE TO FORM 3.pdf

2067-KOLNP-2009-(02-07-2014)-CORRESPONDENCE.pdf

2067-KOLNP-2009-(02-07-2014)-OTHERS-1.pdf

2067-KOLNP-2009-(02-07-2014)-OTHERS.pdf

2067-KOLNP-2009-(27-08-2014)-ABSTRACT.pdf

2067-KOLNP-2009-(27-08-2014)-AMANDED PAGES OF SPECIFICATION.pdf

2067-KOLNP-2009-(27-08-2014)-CLAIMS.pdf

2067-KOLNP-2009-(27-08-2014)-CORRESPONDENCE.pdf

2067-KOLNP-2009-(27-08-2014)-DRAWINGS.pdf

2067-KOLNP-2009-(27-08-2014)-FORM-2.pdf

2067-KOLNP-2009-(27-08-2014)-OTHERS.pdf

2067-KOLNP-2009-(27-08-2014)-PETITION UNDER RULE 137.pdf

2067-kolnp-2009-abstract.pdf

2067-KOLNP-2009-ASSIGNMENT.pdf

2067-kolnp-2009-claims.pdf

2067-kolnp-2009-correspondence-1.1.pdf

2067-kolnp-2009-correspondence.pdf

2067-kolnp-2009-description (complete).pdf

2067-kolnp-2009-drawings.pdf

2067-kolnp-2009-form 1.pdf

2067-KOLNP-2009-FORM 18.pdf

2067-kolnp-2009-form 3.pdf

2067-kolnp-2009-form 5.pdf

2067-KOLNP-2009-GPA.pdf

2067-kolnp-2009-international publication.pdf

2067-kolnp-2009-pct priority document notification.pdf

2067-kolnp-2009-pct request form.pdf

2067-kolnp-2009-specification.pdf

abstract-2067-kolnp-2009.jpg


Patent Number 265674
Indian Patent Application Number 2067/KOLNP/2009
PG Journal Number 11/2015
Publication Date 13-Mar-2015
Grant Date 04-Mar-2015
Date of Filing 01-Jun-2009
Name of Patentee TRADECORP, S.A.
Applicant Address C/. ALCALÁ, 498, 2A PLANTA, E-28027 MADRID
Inventors:
# Inventor's Name Inventor's Address
1 SIERRA, MIGUEL A. UNIVERSIDAD COMPLUTENSE, DEPARTAMENTO DE QUÍMICA ORGÁNICA, FACULTAD DE QUÍMICA, E-28040 MADRID
2 ESCUDERO, ROSA UNIVERSIDAD COMPLUTENSE, DEPARTAMENTO DE QUÍMICA ORGÁNICA, FACULTAD DE QUÍMICA, E-28040 MADRID
3 LUCENA, JUAN J. UNIVERSIDAD AUTÓNOMA, DEPARTAMENTO DE QUÍMICA AGRÍCOLA, FACULTAD DE CIENCIAS, CVII, E-28049 MADRID
4 GARCÍA-MARCO, SONIA UNIVERSIDAD AUTÓNOMA, DEPARTAMENTO DE QUÍMICA AGRÍCOLA, FACULTAD DE CIENCIAS, CVII, E-28049 MADRID
5 GÓMEZ-GALLEGO, MAR UNIVERSIDAD COMPLUTENSE, DEPARTAMENTO DE QUÍMICA ORGÁNICA, FACULTAD DE QUÍMICA, E-28040 MADRID
PCT International Classification Number C05D 9/02
PCT International Application Number PCT/EP2007/064370
PCT International Filing date 2007-12-20
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 06127041.9 2006-12-22 EUROPEAN UNION