The complex compound containing macrocyclic tetradentate ligand, chelate complex and an intermediate connection to obtain macrocyclic tetradentate connections

 

(57) Abstract:

The invention relates to a new stable complex compound containing macrocyclic tetradentate ligand having the structure of formula I, where R1and R2have the same or different values are related or unrelated, and each is selected from the group consisting of hydrogen, halogen, methyl, CF3and, if they are connected, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, are spatial and confirmation difficult, so that the oxidative degradation of complex metal compound is limited, when the complex is in the presence of an oxidizing environment, Z represents a stable to oxidation atom, which metallocomplexes selected from nitrogen and oxygen, X represents an oxidation resistant functional group selected from O or NRswhere Rsrepresents a methyl, phenyl, hydroxyl, auxillou group, CF3or CH2CF3, R3, R4, R5represent fragments of connecting adjacent Z atoms containing structure described in the claims. Also disclosed chelate complex and intermediate sedimentational to get a stable durable oxidation catalyst or promoter catalyst, used in chemical or biological processes. 3 S. and 8 C.p. f-crystals, 10 ill., 7 table.

This work has been supported by the National Institute of health, the program GM-44867 and the National science Foundation, the program CHE9319505. The U.S. government has rights to this invention.

Justification of the invention

The scope of the invention

The present invention relates to a chelate complex compounds of metals, intended for the production of oxidation catalysts, and more specifically, to a durable macrocyclic compounds, officials oxidation catalysts, which are capable of participating in reactions of oxidation by peroxides and other primary oxidants.

Description of the prior art

Although the major source of oxidants in the chemical and biological processes are substances based on transition metals, the oxidation process is much better understood in biology, i.e., many complex selective oxidation reaction, which is carried out in biological processes that cannot be accomplished with the use of a homogeneous synthetic systems. This difference is more noticeable in the field of chemistry of oxidation than in any other is receiving links "carbon-carbon", chemistry oxidation uses a very limited number of technologies of low quality for the implementation of stoichiometric or catalytic processes.

The relatively high cost of a good homogeneous oxidation systems and catalysts due to oxidative degradation of the catalysts. Having high oxidizing ability of complex compounds of transition metals in the middle of a number of transition metals and at the end of it, the same compounds that function as active intermediates in numerous enzymatic reactions of oxidation, and these compounds are difficult to synthesize because such compounds tend to rapid decomposition of the ligands.

In the work of Collins, T. J., "Designing Ligands for Oxidizing Complexes," Accounts of Chemical Research, 279, Vol. 27, No. 9 (1994), based on synthetic metals oxidizing agents are divided into two basic classes - compounds with redox activity against metals and oxidizing agents metals matrix type. In systems with redox activity with respect to metals, oxidizing component contains a metal ion, which is in the directly the townsman tima with oxidizing metal ions. Oxidants matrix type not subject to such restrictions, as the oxidizing component is further away from the metal ion, but the matrix system is only suitable for mild oxidation, in contrast to simple oxidation that requires highly metallookandfeel. Oxidants in the form of metal ions in oxygenating enzymes are often the catalysts strict oxidation, such as the interaction of methane-monooxygenase, i.e., the oxidation of methane to methanol with oxygen as the primary oxidant. The role of metallookandfeel these enzymes belong to the type of oxidizing agents reducing agents. The main problem with the transference of this proposed enzymatic mechanism in artificial systems is to develop a sustainable system of ligands that can withstand extremely strong oxidizing agents - metal ions, causing cleavage of the atom.

In the article "Accounts" Collins describes the construction-oriented" approach to obtaining ligand and chelate complex compounds of metals which are resistant to oxidative degradation. In the article "Accounts" also described several diamino-N-diperoxide acyclic, tetraamido-N - macrocycle and transition metals, situated in the middle of a number of transition metals and at the end of it, and the metal ions are located in this state that offer unparalleled high oxidizing ability, which was achieved by using macrocyclic ligands.

Although it is enough to obtain the above ions with very high valency in a stable form, including strong oxidizing agents engaged in the transfer of electrons, however, see "Accounts" set of rules is insufficient for solving the problem of encapsulating especially powerful metallokarkas, similarly as it happens in monooxygenase enzymes, so that the oxidant had enough life in order to carry out the processes bimolecular oxidation. The solution to this problem lies in the structure of the ligand described in this application.

Brief description of the invention

The required stability of the ligand and the derived complex compounds was achieved by using compounds with macrocyclic tetradentate ligand of the present invention. Compounds according to the invention have the General formula:

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where R1and R2have the same or different values are vasanthakumari form strong links with R1and R2and with the cyclic carbon are spatial dull and conformationally difficult, so that the oxidative degradation of the metal complex compounds is limited, when the metal complex is in the presence of an oxidizing environment. The obstruction prevents the adherence of conformers, which lead to intramolecular oxidative degradation.

Z is a donor atom, preferably resistant to oxidation atom, forming a metal complex, such as N or O, optionally bearing hydrogen;

X represents a functional group, preferably resistant to oxidation functional group, such as O or N Rswhere Rsrepresents a methyl, phenyl, hydroxyl, auxillou group, -CF3or-CH2CF3;

R3is a piece that connects the adjacent Z atoms and consisting of:

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or

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R4is a piece that connects the adjacent Z atoms and consisting of:

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or

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where R6and R7, R8and R9and R10and R11, R12and R13, in pairs and as a group have the same or different values and each is a fragment, connecting the adjacent Z atoms, and consisting of: (i)

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and

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where R14- R17have the same or different values and each represents alkyl, aryl, halogen, or CF3and (ii) aryl groups, including mono-, di-, tri - and Tetra-substituted aryl and heteroaryl substituents:

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where each Y may be any Deputy or deputies, but, preferably, halogen, hydrogen, alkyl, aryl, amino, substituted amino, nitro, alkoxy, aryloxy and combinations thereof. Aryl group replaces four substituent, and the carbon atoms to which they are attached.

The present invention relates to new changes in the structure of the macrocycle, which increase the stability of Tetra-Aza macrocyclic ligands, through which you can obtain a system of ligands, which supports catalysis based on intentionally high-level intermediate metallogalogennye similar to the system of ligands for monoxygenase. The mechanism of decomposition, which took the above changes were totally unexpected. Most importantly, the new system described here support the catalysis with extremely desirable on the and for a wide range of technological oxidative processes where it is possible to use chemically effective and efficient catalysis.

Complex compounds of transition metals with macrocyclic ligands in the past been used as oxidation catalysts. Proprietary systems include porphyrins and phthalocyanines, halogenated porphyrins and ligands related to porphyrins and substituted tricyclodecane and related macrocycles. All these systems are fundamentally different from the system of the present invention. First, macrocyclic tetraamide are tetraoninae and strong donors, so that the ligands of the present invention make available such forms of metals in which they have a high valence and the reactivity and efficiency of the ligands according to the invention is much higher than any other macrocyclic compounds used for this purpose. Secondly, the macrocyclic compounds of the present invention can be obtained in the form of compounds, strongly protected without recourse to the halogen substituents (or with them) - not halogenated compounds cause less damage to the environment. Thirdly, the macrocyclic complexes tetraamido this izobreteny the th as water, in which dissolved salts containing various metal ions.

Tetradentate macrocyclic compound of the present invention is intended for the formation of complex compounds with metal, preferably a transition metal, and preferably with a transition metal selected from group VI (Cr group), VII (group Mn), VIII (Fe), IX (group Co), X (group Ni), XI (group Cu) of the Periodic table of elements, to obtain the corresponding chelate complex.

Thus, the present invention includes a chelate complex of the formula:

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where M represents the metal, Z is a donor atom, such as resistant to oxidation atom, forms a complex with the metal, which is described above as macrocyclic tetradentate compound of the present invention, and Ch1Ch2Ch3and Ch4are resistant to oxidation components chelate system, which are the same or different and which form a five-, six-membered ring with an adjacent atoms ZMZ.

In a preferred embodiment of the invention the axial ligand L1associated with metal. The ligand L1is labile, since it C is the oxidant. Labile ligand dissociates in solution and will be replaced by the oxidant, typically the transfer agent O-atom, but may be replaced by any oxidant, which can serve to activate the metal ion to carry out the functions of the catalyst. Preferred labile ligands include Cl-anion ions Gulidov in General, CN-, ROH, NH3or any amine, carboxylate, phenol or phenoxide, nitrile, pyridine, simple, ether, sulfoxide, ketone or carbonate.

It was found that in places oxidation in complex compounds of iron, representing the macrocycles containing aromatic rings (one electron oxidized over FeIII) can be manipulated by choosing the axial ligands, and also with the help of substituents in the aromatic rings. Strong s-donor anionic axial ligands (CN-promotes the oxidation of the metal in the center, i.e., FeIV, while the weaker donors (Cl-encourage localized on the ligand oxidation. Oxo-compound is an intermediate form chelate complex and it is believed that in some cases it functions as a real catalyst. In other cases, the chelate system may be the only place oxidation, or CLASS="ptx2">

Chelate group Ch1preferably represents the radical, as described above Rs in macrocyclic tetradentate connection. Ch2and Ch3meet the radicals R3and R4macrocyclic tetradentate compound described above.

Ch4, preferably, is a binding part of the General formula X= CC(R>>)2'C=X, where (R>>)2equivalent to R1and R2as described above, and X represents an oxidation resistant functional group described above.

R1and R2represent key deputies in the design of a stable chelate complex and catalysts of the present invention. R1and R2preferably represents methyl, CF3hydrogen or halogen, or can form, together with the carbon atom to which they are both attached, a ring, such as four-, five - or six-membered ring. It is believed that intramolecular interactions between the substituents R1and R2in previously known complexes and Oxelosund in the current catalytic system contribute to the rapid degradation of the chelating ligand, as evidenced by the experience. Cm. Fig. 1, g is the data correspond to the data in Fig. 1), which is known catalytic compounds with diethyl substituents in positions R1and R2sensitive to oxidative effect, so while it was possible to observe the catalytic oxidation system ligands simultaneously underwent slow decomposition by oxidation. All tetraamide macrocyclic compounds described in Collins Accounts of Chemical Research, which we quoted above, include diethylene substituents in positions R1and R2. Thus, to date none of the complex compound of transition metal, having a macrocyclic tetraamide ligand, could not act as an oxidation catalyst for an extended period of time required for the catalytic reaction.

Description of drawings

Fig. 1 schematically illustrates the proposed path of oxidative degradation of a catalytic system consisting of compounds II and peroxides, due to intramolecular interactions between dieselnoi component and oxoacridine ligand.

Fig. 2 illustrates the method by which conformational constraints prevent oxidative degradation of the carbonyl group.

Fig. 3 (a) and (b) the e shows the components of the connection - branch, the linker and the bridge.

Fig. 4 is a view of recirculated systems metallocycles.

Fig. 5 is a schematic representation aminosalicylic macrocyclic complex metal covalently associated with the sea surface.

Fig. 6 illustrates several chelate complexes derived from macrocyclic ligands according to the invention.

Detailed description of preferred embodiments of the invention

The preferred embodiment tetradentate macrocyclic compounds of the present invention is the following:

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in which R1and R2have the same or different values, and each of them is selected from the group of substituents, which are directionspanel form strong intermolecular bonds with R1and R2and with the cyclic carbon are spatial dull and conformationally difficult, so that the oxidative degradation of complex metal compounds is limited, when the complex is in the presence of an oxidizing environment. Low conformational freedom of certain types of compounds prevents the acquisition of the stake is preferably resistant to oxidation atom, forming a complex with a metal, more preferably N or O, bearing, if necessary H. Preferably, at least three Z was a N. X represents a functional group, preferably resistant to oxidation functional group, and more preferably O or NRswhere Rsrepresents a methyl, phenyl, hydroxyl, auxillou group, -CF3or-CH2CF3.

R6, R7, R10and R11have the same or different values, and each is chosen from the group comprising alkyl, aryl, halogen and CF3. R5is a fragment of a connecting adjacent Z atoms, and it is chosen from the group comprising (i)

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and

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where the radicals R14for R17have the same or different values, and denote alkyl, aryl, hydrogen, halogen, CF3or combinations thereof, and (ii) aryl group, including

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where Y represents halogen, hydrogen, alkyl, aryl, amino group, substituted an amino group, a nitrogroup, alkoxy, aryloxy and combinations thereof.

Compounds of the present invention form a stable durable catalysts for oxidation and predetonator. For a few who ICEM represent such catalysts, which carry out the oxidation. In many cases, the exact mechanism of catalytic action is unknown and therefore the exact role of the chelate system according to the present invention in one or another of the oxidation reaction is not known. In the text of this application the term "sustainable oxidation catalyst" means that when the catalyst is added to the solvent in the presence of an oxidant such as peroxide, the half-life of the activated form of complex metal is 30 seconds or more. The half-life is the time during which half of the metal complex is decomposed or degraded.

It was found that, in accordance with a preferred variant of the invention a new stable compounds differ from the known compounds of only one component. After replacing diethyl substituents R1, R2in known tetraamine compounds in dimethyl substituents, former fragile short-lived chelate complexes was turned into a stable long-lasting complexes, which are very resistant to oxidative degradation. What seemed to be a slight change in the structure, in fact, became the key to a new class of sustainable durable catalyst for the connection of the corresponding ethyl substituent. It was found that any of the substituents R1, R2that are directionspanel or which form strong links with the cyclic carbon, or which are spatial or conformationally difficult, so they can't engage in an intramolecular interaction with the axial Oxelosund will also form a stable catalysts, or precatalysts of the present invention.

The importance of bond strength and/or conformational constraints can be seen from the following.

To create media for the oxidation catalyst, each component of the ligand system must be resistant to oxidative degradation. A key factor in the stability of the groups R1and R2found watching one of the most illustrative case. As shown in Fig. 1 aquacomplex iron (III) interact with hydroperoxides to obtain the specified oxocomplexes, which, as shown, has a catalytic properties against oxidation of NITRILES containing C-H bond, to receive ceanography. However, in the process of catalytic reactions ligand system slowly decomposes and it is assumed that such degradation occurs when the CTD is dentonvale ring, contains product degradation, marked III (Fig. 1). Molecular models show that highly strained conformation of the chelate ring containing Ch4required in order to bring detachable H-atom close to separating the O-atom. Compound III is uniquely characterized by different analyses, including mass spectrometry, 1H and13C NMR, IR, elemental analysis. Simultaneously with the observed degradation of the system is the catalytic oxidation of the weakest C-H-bond in a series of NITRILES [(CH3)2CHCN, CH3CH2CN, CH3CN, CD3CN], which are used as solvents. The products are mixtures of oxidation products of NITRILES. So, if tert-butylhydroperoxide is the primary oxidant, the mixture of products (CH3)2CHCN substrate contains (CH3)2C(OH)CN, (CH3)2(CN)COOC(CH3)3, (CH3)2(CN)COOCH3, (CH3)2C=O, (CH3)3SON. It was also shown that, while the mixture of products assumes that happens the auto-oxidation of free radicals, where the role of iron complex II (Fig. 1), will be to initiate the process, the auto-oxidation of free radicals cannot be dominan the s18O2is too low for the reaction mechanism consistent with the process of auto-oxidation of free radicals. By replacing the CH3- CH3CH2- in the provisions of R1and R2degradation of ligands strongly suppressed, so that the oxidation of nitrile itself is the dominant oxidizing ability. This suppression of degradation of ligands by replacing CH3- CH3CH2- you can recognize the result of the increased bond strength of C-H in CH3relatively CH3CH2- approximately3kcal/mol-1whereby the speed of separation of the H atom with Oxelosund slows down about three times. Because it is obvious that separation is an extremely important factor degradation, the orientation of the detachable H-atom relative Oxelosund also plays an important role, because this orientation determines the distance of approach and response branch is very much dependent on the distance. Molecular models show that if cyclopentadienyl fragment used to replace ethyl groups, R1and R2then methylene group C-H, is equivalent to the group, separated from the ethyl C-H group is not able to reach Oxelosund without t is ethyl. Thus, conformational restriction leads to a dramatic increase in the resistance of substituted therefore chelate complex to oxidative degradation.

In the structure shown in Fig. 2, oxoprop and methylene H restricted from such a close proximity, which may occur in the case of ethyl, because the methylene group cyclopentene Deputy cannot freely rotate to bring the two groups are so close to each other.

Compounds of the present invention are macrocyclic, consist of four anionic donor ligands, resulting in a virtually planar tetradentate platform, which can form a complex with the metal and the axial ligand to obtain Gelato/catalytic system according to the present invention. The preferred structure is stable ligand - macrocyclic tetraamide ligand having no hydrogen atoms on the N-amide donor groups. When coordinating with metal ions of five - and six-membered chelate rings are the most stable. The substituents can be different, provided that they satisfy the above requirements. This is especially important in odnoklassnik tetraamine ligands described in Uffelman, E. S., Ph.D. Thesis, California Institute of Technology, (1992). Otherwise (and preferably) the compounds according to the invention it is possible to synthesize new ways.

A new method of synthesis allows the synthesis options that cannot be synthesized by using a known method of synthesis on the basis of the azide. However, when you change the macrocycle is important to keep the overall wiring diagram. The macrocycle will consist of 5 - and 6-membered rings, in the form of schema 5,5,5,6, schemes 5,6,5,6, schemes 5,6,6,6 or schema 6,6,6,6, about which more will be said below.

A new method of synthesis is usually as shown in scheme 1 and 2. Specific examples of the application of a new method for the synthesis of some specific macrocyclic tetraamido shown in scheme 3. For convenience, the classification of raw materials, which consist of diamines functional groups, sometimes referred to as "bridges" (), source materials consisting of different functional groups, sometimes called "linkers" (L), and the raw materials consisting of amine/acid functional groups is sometimes referred to as "branches" (A). Cm. Fig. 3(a) and (b). Branch macrocyclic compounds are more stable than linkers, they resist degradation.

Scheme 1 (see the end of the op-A-), from aminocarbonyl acids by means of a new method of synthesis. Intermediate compound containing diamide-dicarboxyl, sometimes called "macromineral intermediate connection", or just the intermediate compound (A-L-A), previously obtained without the use of protective groups by the reaction of selective dual-joining, which is aminocarbonyl acid (acting in the role of "branches", A) and the activated derivative of malonic acid (acting as a linker, L), the solvent is heated to obtain microlensing intermediate compounds. Microlingerie intermediate connection then connect with a diamine that acts as a bridge () in another reaction selective dual accession, during which the applied solvent, the agent connection and heating. The methodology of synthesis is very simple and allows you to use a wide range of functional groups. A wide range of macrocyclic tetraamido with different electronic or spatial deputies, received such a way and at a high yield of product.

Scheme 2 (see the end of the description) is a generalized scheme of the synthesis of macrocyclic tetraamido, the ima is vicinage method of synthesis. The choice of accommodation-aminocarbonyl acids as starting materials applies almost the same approach as for the choice of accommodation-aminocarbonyl acids as starting materials. For some aminocarbonyl acids using protective groups may be desirable, as shown in Scheme 2. Microlingerie intermediate compound (A-L - A) get through pre-reaction selective dual accession, during which the ester-aminocarbonyl acid as branches (A) and the activated derivative of malonic acid as a linker (L) in the solvent is heated to produce an intermediate substance, which after removal of the protective group can be attached to diamino the bridge (In) during another reaction for selective connection to a wide range of substituted macrocyclic tetraamido with advanced ring size compared to tetraamide, which were obtained from aminocarbonyl acids.

Microlingerie intermediate compound (A-L-A) can be obtained in large quantities during periodic or continuous process through direct interaction substituted malonyl - dihalide with a solution (preferably pyridines the protective groups at temperatures preferably, lower than or equal to about 70oC. Some examples require the use of protective groups, and these reactions usually give a good output. The intermediate connection can be divided into portions and each portion is then interact with a wide range of djaminovich compounds forming bridges with different spatial or e-substituents, in the presence of the agent connection. For-aminocarbonyl acids closure phase ring takes from 48 to 120 hours and should ideally take place with virtually no moisture (see figure 3 at the end of the description). A wide range tetraamide macrocycles with carefully selected electronic properties, it is possible to synthesize at considerable savings in comparison with the known azide method.

Figure 3 is a specific example of a macrocyclic tetraamido having the configuration of (B-A-L-A-), aminocarbonyl acid as starting material, aminocarbonyl acid is mixed with activated malonate in pyridine at temperatures below 70oC. After the reaction is selective dual attach completed through 72-144 hours, emit microlingerie intermediate compound (A-L-A the tick compounds in the presence of the agent, the calling connection, preferably PCl3or pivaloyloxy. The reaction leading to the closure ring, the reaction of the double-accession flows distillation during 48-110 hours, and then the desired macrocyclic tetraamide isolated in good yield of the reaction product.

Synthesis of stable to oxidation macrocyclic tetraamido requires that all H atoms, from to donor atoms have been replaced by more resistant to oxidation by groups such as alkyl, halogen, aryl or heterocyclic substituents.

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Structure 1 shows the key intermediate connection upon receipt of the catalyst according to the present invention is resistant to oxidation macrocentra (branch-linker-branch Arm - Linker-Arm). This molecule can be easily synthesized in a single step without the use of protective groups by direct acylation and methylalanine using dimethylmaleic - dichloride.

In an alternative embodiment of the invention in the method according to the present invention sequentially attaching/removing the protective group to create a protected form microlensing intermediate compounds. After removal of the protective the La creation tetraamide of the macrocycle. Similarly consistent attaching/removing the protective group can be applied in relation to substituents present on bridge fragment to expand the bridge substituents, which can be used for the reaction of macrocyclization.

Both variants of the method of the present invention is based on the use as starting materials amines or carboxylic acids, which are listed in Table 1. Table 1 lists the raw materials in several forms, containing amino groups and carboxylic acid in the form of related groups, protection/activated groups, and hidden groups. In Table 2 uses the same category due to restrictions on the size of the chelate ring (5 - and 6-membered chelate rings are preferred) to identify the source materials suitable for the synthesis of macrocyclic chelate tetraamine compounds having the required five - or six-membered ring.

In the text of this application, the term "related groups" (indicated in italics in Table 1) are indicated preferred synthesized functional groups. The term "protective/activated group" refers to those goruppa, who should not contain easily identifiable part of the related group, but which can easily be converted to a related group, or similar group containing protective/activated group. More detailed examples can easily be found in the "Green and Green, "Protective Groups in Organic Synthesis", John Wiley and Sons, New York (1981). A complete list of protective/activating groups is the work of G. A. Fletcher and J. H. Jones, "A List of Amino-Acid Derivatives Which are Useful in Peptide Synthesis", Int. J. Peptide Protein Res. 4, (1972), p. 347-371.

Structure 2 below in order to explain a brief notation in Table 2 and Table 3, which shows the size of the chelate rings (including metal ions), which was formed when this macrocyclic ligand coordinated to the Central transition metal.

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Amin will be denoted "a" carboxylate "c".

Dashes (-) are marked by amide linkages. Each line must connect the following "a" with a leading "c", or Vice versa, and the final dash returns to the beginning. Structure 2 illustrates a macrocyclic ligand (5,5,6,5), shown in metallocarboranes form with the specified size of the chelate rings (including metal ions). Going counterclockwise, specific ispolzovat form (=) functional groups for each of the source material is shown graphically in Table 2 below, and the possible combinations of protective/activated groups (p/a group) or hidden (h) of each starting material shown in the form of tablets. Variable items marked with a dot (). The underlined combination of letters and numbers on the side are shortened schemes and relate to the size of the chelate rings formed when the specific source material is introduced into the macrocycle and coordinated relative to the metal center (see Structure 2).

The full range of macrocyclic tetraamide compounds that can be synthesized from starting materials described in Table 2, in General terms, are given in Table 3. Each unique combination is indicated graphically and marked reduction both in Structure 2, above.

Separate the raw materials for bridge branch and the linker can either be purchased or synthesized by conventional means. Examples of the synthesis of the few raw materials, which are not given in this text in the Experimental part. Effective alternative method of obtaining substituted and unsubstituted malonate described in A. P. Krapcho, E. G. E. Jahngen, Jr. and D. S. Kashdan. -carbalkoxylations of carboxylic acids. A general synthetic route to monoesters ofmalonic acids", Tet. Lett. 32, p. 2721-2723 (1974). Sustainable ICEM not have to resort to the use of those species, which contain a strong N-N, such as oxides, hydrazine, and azo-components.

Schemes 4-6 (see below) graphically depict the substitution in various positions shown (in table 3. In the remaining part of this section discusses in General how to choose the substituents R, and in the form of tables list some specific examples of substituted starting materials of the bridge branches and linker.

Replacement on the same site

Source materials containing only one variable position, replace the carbon atom bearing two R groups, fragment-C(Ra)(Rb)- (in this case, the dash (-) denotes single bond in contrast to the amide bonds).

In figure 4 one variable position is always replaced by the fragment-C(Ra)(Rb)-.

To make a substitution at any one of an R-group on the fragment-C(Ra)(Rbcan be the same or different and are selected from the group consisting of hydrocarbons and hydrocarbon substituted by a heteroatom (e.g. , halogen, N, O, Si, P, S). The specific choice of R-groups, in addition to R1and R2perform one of the following types/subtypes groups either separately or in combination (e.g. the e acid, carboxylic acid having hidden or protective/activated groups (see Table 1), esters, ethers, amines, amines, having hidden or protective/activated groups (see Table 1), imine, amides, nitro, sulfonyl, sulfates, factorily, phosphates, silyl, siloxanes, alkyl, alkenyl, quinil, Gelovani, aryl and compounds selected from biological systems, e.g. natural or synthetic amino acid side chain, a heterocyclic ring, lactams, lactones, alkaloids, terpenes (steroids, isoprenoids), a lipid or phospholipid chains.

To replace one node merging groups of Raand Rbin a position that is not where the substitution occurs, but to the place of substitution gives the species associated dual connection with the site, such as oxo (=O), Imin (=NRa), or substituted vinyl group (=C(RaRb). Education Iminov or substituted vinyl groups is a kind of migration on the host. If the original group Raand Rbmerged in a place that is not a place of substitution and no substitution, then forms a cyclic ring structure. If formed such cyclic group, more R substituents on cyclicaly the possibility of further m R groups on one or more nodes to more oxoprop, Iminov, substituted vinyl groups, or Spiro rings, benzene, substituted benzene, heterocyclic, substituted heterocyclic, cycloalkyl, substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl rings). The preferred dimensions Spiro/cyclic rings are four-, five - or six-membered ring.

Substitution on multiple nodes, see figure 5.

In scheme 5 replacement on two variable positions can be accomplished in two fragments-C(Ra)(Rb)-, or two changed positions can be combined, receiving part aryl or heterocyclic rings.

For replacement at multiple sites, substitution on the individual provisions of the-C(Ra)(Rb)- produce as well as the substitution on a single node. In addition to the types of overrides for a single node, you can combine or link multiple sites together through condensation of R groups located on different nodes in places that are either (a combination of) or are not (connection) places of connection. The combination of places that are adjacent to each other, leads to the appearance of ethylene fragments (-C(Ra)= C(Rb)-) forms of address R GRU is of seats, which do not adjoin each other, leads to cyclic structures, such as Spiro-rings, benzene, substituted benzene, heterocyclic, substituted heterocyclic, cycloalkyl, substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl rings. Five - and six-membered rings are preferred.

If formed a cyclic group, or if there are residual R group remaining after combination of the neighboring places, the remaining R groups and the substituents on the cyclic groups choose the same as for a normal substitution on a single node or on multiple nodes (including the possibility of subsequent condensation of R groups to more Spiro - rings, benzene, substituted benzene, heterocyclic, substituted heterocyclic, cycloalkyl, substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl rings).

The important point is that the substitution and a single node and multiple nodes may come in the form of a recursive function, e.g., substituted o-phenylenediamine substituted heterocyclic o-phenylenediamine substituted spirocyclic heterocyclic o-phenylenediamine, etc.

<- C(Ra)(Rb)-, or two changed positions can be combined, receiving part of the aryl or heterocyclic ring, where the third position is replaced by fragment-C(Ra)(Rb)-, or three changing position can be combined to education part of the condensed diaryl, condensed aryl heterocyclic ring or condensed digitalicing rings.

Some examples of commercially available and/or synthesized starting materials for linkers, branches and bridges are given in Tables 4, 5 and 6 respectively. Macrocyclic tetraamide connection with the desired configuration of chelate rings, shown in Table 3, i.e., 556, 5566, 5656, 5666 or 6666, and their variants, can be obtained using the General principles of selection and combination of raw materials for various chelate of the configurations shown in Table 2, i.e., related, protective/activated or hidden groups, with subsequent selection of a specific source materials from Tables 4, 5 and 6. The use of such functional groups, and a similar source materials in a new method of synthesis allows to obtain macrocyclic tetraamide compounds having chelating configuration of kouchini deputies, which have a comparative oxidation resistance. The icon in the tables indicated substituents, which are very resistant to oxidation.

Table 4 shows some members of the derived malonate dicarboxylic acids, i.e., linkers, which are used to produce macrocyclic tetraamido are either in the form of related, either in the form of hidden groups or protective/activated groups.

Table 5 identifies some typical - and-aminocarbonyl acid, i.e., the branch of interest to obtain macrocyclic tetraamido as a parent, hidden, or protected/activated groups.

Table 6 identifies some of the typical diamines, i.e., the bridges of interest in obtaining macrocyclic tetraamido, as the parent, hidden, or protected/activated groups. Amine and protected/activated or latent amino group are used interchangeably.

The list n,n + 2-diamines much shorter than the list of other derivatives, to a large extent this is due to the fact that the synthesis of the desired n,n + 2-diamines more complex than n,n + 1-diamines.

Some specific examples of what was slagalice during retrosynthesis before the formation of amine equivalent (Amin, nitro, azide, isocyanate, etc. , see Table 1) and equivalent carboxylic acid (acid, ester, acylchlorides, nitrile, etc., see Table 1).

Bridges and linkers from Table 7 retain local twofold symmetry, while all branches lead to a five-membered chelate rings.

Some specific examples of bridge (Bridge=), branch (Arm=A) and the linker (Linker=L)

Because the R groups do not participate in the synthesis reaction, there are many options. However, as mentioned above, in order to obtain a stable to oxidation of the compound and the catalyst, to the R groups is necessary to apply certain limitations. Enough to know that the removal of a hydrogen atom occurs between the R-substituents of the linker and the axial ligand, bound to the Central metal atom of the final chelate system, Such removal then leads to oxidative decomposition, as shown in Fig. 1. Molecular models showed that the conformation of the "baths" six-membered ring of the linker in macrocyclic complex, the H atoms of the methylene ethyl groups can achieve oxygen atoms in the complex Fe-oxo. This fact, as well as other data support the mechanism shown in Fig. 1, and explain the preferred macrocyclic compounds should be such so they reduced the response branch of the H-atom and thereby slowed oxidative degradation. To do this, the group R1and R2compounds of the present invention shall be those groups that have a high bond strength, do not enter into the reaction, or that are not available for the axial ligand, such as spatial or conformationally employed group. You can use any such connection or any combination of such signs. The latter can be achieved by restricting the conformational freedom of the groups R1and R2so they will just close enough to each other to start the reaction. In this text the high bond strength of C-H means over 94 kcalmol-1or more than 85 kcalmol-1for spatial unavailable C-H bond.

Maloata part of the linker is the most sensitive part of the macrocyclic ligand. Preferred R groups on the linker include methyl, halogen, hydrogen, CF3and spirocyclopentane or spirocyclohexane ring in place R1and R2.

Significantly less limited selection of R-substituents for branches than for the linker because of the stability of ego could oxidize C-H groups in contact with the axial Oxelosund. Thus, the R group and aminocarbonyl acid can also be selected in order to find substitutes for the target molecule, and to provide certain properties of this molecule. The macrocycle can be symmetric and asymmetric. For asymmetric macrocycles use two different amino acids as starting materials, and the resulting macrocycles are a mixture of symmetric and asymmetric variants. Two options can be divided by known methods of separation. A few examples of the compounds of the present invention is shown below.

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After macrocyclic tetradentate ligand was obtained macrocyclic compound can be converted into a compound with a variety of metal ions, preferably a transition metal, and most preferred transition metal selected from metals of the VI, VII, VIII, IX, X or XI group of the Periodic table for the formation of a chelate complex of the formula:

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where M represents the metal, Z represents a stable to oxidation atom, forms a complex with a metal, such as N or O, L1is any labile ligand, Ch1Ch2Ch3and Ch4dinasovymi or different and which form a five - or six-membered ring with an adjacent atoms ZMZ.

Complexation achieve the following way. Macrocyclic ligand is dissolved in a solvent, which is a carrier, usually in THF, to produce the removal of protons by treatment with a base, preferably bis-trimethylsilylmethyl lithium, diisopropylamide lithium, tert-bootrom lithium, n-bootrom lithium or phenyl lithium. Will fit any basis with which you can remove the protons in place of forming a complex with the metal, i.e., the amide N-H protons tetraamide connection. Preferred are coordinarussia organic soluble base. After ligand was removed protons, add metal ions. The obtained intermediate compound, the ligand of the metal with a relatively low valence, then subjected to oxidation. Stage oxidation, preferably, carried out with air, chlorine, bromine or benzoyl peroxide to obtain a chelate complex of a metal, usually in the form of a lithium salt. The exchange reaction of the resulting complex to obtain tetraalkylammonium, tetraphenylphosphonium or bis(triphenylphosphonio)ammonium (PPN) salts results in chelate complexes of metals, which are easier to clean, compared with complexes, sodeci oxidation.

If the complex is then combined with a strong oxidant, giving the O atom, preferably a peroxide such as hydrogen peroxide, tert - butylhydroperoxide, cumylhydroperoxide, or nagkalat, I get the oxo intermediate connection ligand metal IV, V or VI group. When resistant to oxidation deputies used to obtain the skeleton of the ligand, as intermediate compounds were developed containing the carbonyl group of the connection. These contain the carbonyl group of compounds with a high valence are active agents of migration in a number of catalytic oxidation reactions.

When metals with low valence exposed to peroxide or other oxidant containing [O], the metal attracts and binds oxygen from the oxidant. Depending on the metal bond between the metal and oxygen can be very strong, or it can be strong enough to remove oxygen from the oxidant for later transfer to another component.

If the metal is a metal ion of group III, the obtained exocoetidae in General will be a metal ion V group. If the metal is a metal ion of group IV is and V groups with a second plot of oxidation on the ligand, i.e., the radical ligand/cation. Combined stabilizing effect of the macrocyclic ligand and part number of d electrons in the center, which is a metal, in the process of changing the degree of binding to Oxelosund, allows to obtain complex compounds with transition metals (with small group numbers), which form very strong bonds between oxygen and metal and thereby gain stable oxides. Transition metals that belong to the groups from medium or large rooms, have a tendency to remove oxygen from the oxidant and link Oxelosund to obtain a reactive intermediate compounds. In the system of the ligand-metal, obtained by the method according to the invention, transition metals, which belong to the groups from medium or large rooms, tend to facilitate the transport of oxygen.

In addition to the stabilizing action of the ligand affects the properties of the metal. Controlling the choice of metal, the electron density in the macrocycle, the charge of the complex and durability of connection/communication with the coordinated Oxelosund, complex ligand/metal can be precisely configured to implement all the possibilities for the transfer of oxygen from the stable of the of the axial ligand L1is labile, because it takes its position relative to the metal up until chelate system is not introduced into the solution containing the oxidant. Labile ligand will dissociate and replaced oxidant, often the agent carrying an O atom, but can also be replaced by any other oxidant, which can be used for activating metal ion to perform catalysis. Preferred labile ligands include, among other anion Cl-the ions halides in General, CN-H2O, OH-, ROH, NH3or amine, carboxylate, phenol or phenoxide, pyridine, simple, ether, sulfoxide, ketone, or carbonate. The plot of oxidation can choose on the axial ligands and substituents on the ring.

Received macrocyclic compounds with spirocyclohexane deputies, and it was found that such substituents do macrocyclic compound is very hydrophobic and, interestingly, soluble in pentane and other light saturated aliphatic solvents. Long-chain substituents, such as modelline chain or phospholipid chain, make macrocyclic compound is soluble in the membrane.

Spirocyclohexane titlename substituents, so that changes the normal synthesis of amide intermediate compound in the first step of the method according to the invention.

Synthesis of bis-spirocyclohexane microlensing intermediate compounds was carried out by adding drop by drop Alliluyeva reagent in multiple aliquot quantities, preferably in three entered after a certain period of time. The best results were obtained when, after a twelve hour intervals followed by long periods of interaction. If the interaction was not very long, the yield was lower. The sequence of reactions shown in the scheme below. Cyclohexane can be used to separate oxazalone form metroliner from other reaction products, or you can add water to conduct hydrolysis oxazalone on the spot. Hydrolysis of the intermediate oxazalone gives an increased yield of the desired bis-tsiklogeksilnogo of microlender.

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Containing the cyclohexyl microliner then ready for the stage of closing the ring; this is carried out in the same way as for other intermediate compounds according to the invention. However, due to the increased stability of the intermediate macrocyclic compounds, soderjaschih preferred way of closing rings. Usually the crude reaction products, which represents a macrocyclic compounds extracted in an organic solvent such as CH2Cl2. A solution of CH2Cl2washed with acids and bases to remove impurities and by-products, which contain acidic or basic functional groups, and for the implementation of the hydrolysis of any intermediate compounds containing oxazole. Cyclohexyl-tetraamide macrocyclic compound is not very susceptible regular cleaning by washing with acids and bases, so the treatment will receive a mixture of approximately 1: 1 bicyclogermacrene and bis - cyclohexyl-tetraamide macrocyclic compounds. Extraction in a mixture of pentane gives a clean separation. Macrocyclic compound is insoluble and it is isolated in the form of a powder, while soluble in pentane fraction can evaporate to obtain large crystals of bis-cyclohexyl-oxazalone.

It was observed that the addition of the substituted malonaldehyde in excessive amounts increases the output metroliner at the optimum ratio of about 2 mol of amino acids by 1.35 to 1.5 mol of the substituted malonaldehyde. The product mixture is more product. The yield of product obtained by the method according to the invention, is greatly improved if the reaction solution is to exclude water during reactions on connecting the ring.

You can also use pyridinediamine. The known method for the synthesis of azides, which includes the recovery phase, during which also restored the pyridine ring, it is not possible to obtain macrocyclic compound with pyridine bridge. Variants of compounds containing an additional amino group, it is rather difficult to synthesize using known methods of synthesis. Variants of compounds containing an additional amino group, are of considerable interest because they allow you to associate a macrocyclic compound or a metal complex with a base, such as a polymer or sand, or with other molecules or substrates having functional groups that are covalently linked to the amine. Groups that are covalently bound with amines, are well known and include (in the form of complexes), for example, alkylamines followed, amides, sulfonamides, Emini and other hidden or protective/activated forms, see Table 1.

Synthesis of variants of compounds containing an additional amino group, usually the shares includes strategic and selective introduction of protective amino group (ndimethylacetamide) origininfo group (the Bridge). Secured form of the bridge acetamido-diamine, then suitable for the reaction of the closing ring through the standard synthesis of diamine + intermediate linker, as described herein. A longer reaction period closing ring is required in order to achieve macrocyclization and explain it by the fact that between attached oxazalone and acetamide group is formed of unwanted hydrogen bond, which slows the desired reaction macrocyclization.

After it was synthesized macrocyclic compound containing additional protective amino group, as shown in reaction Scheme 5, this connection can be metallikat cobalt. The removal of the acetyl protective groups to obtain complex macrocyclic compound of cobalt, which is easy to attach to the media. The best results were obtained by reallylove additional amino group of acryloyl-chloride to obtain macrocyclic compounds with additional vinyl group, linked to the amide group.

Then this connection can be copolymerisate with twelve excess of various acryloyloxy monomers to obtain an acrylic polymer that contains Makoto schematically shown in Fig. 5.

By joining macrocyclic complex compounds of cobalt to the polymer or other carrier, the metal can be recovered and recycled through the system, schematically shown in Fig. 4. Environmentally toxic metals, such as CrVIyou can substitute more environmentally friendly reagents oxidation, such as CoIVor CoIIILIwhere LIrefers to oxidation, in the centre of which is the ligand.

It Is Evident From Fig. 4 shows that after the desired oxidation process attached oxidant can be recycled, for which it is collected and re-oxidize the primary oxidizing agent such as hypochlorite, bromine or using electrolysis. Using the attached macrocyclic metal compounds, as expected, it will be possible to get an effective way to greatly reduce levels of disposal of spent toxic metal compounds in the environment.

Experimental part

Synthesis of stable to oxidation tetraamine ligands.

Materials: All solvents and reagents were substances by chemical class (Aldrich, Aldrich Sure-Seal, Fisher) and were used as received. The analyses were conducted is2in the chamber with three compartments, using vitreous coal disk working electrode (A ~ 0,0078 cm2or 0,071 cm2), of platinum wire counter-electrode, and the electrode of saturated sodium chloride calomel (SSCE) as a reference electrode. As solvents used CH2Cl2(Aldrich Sureseal) or CH3CN (dried over CaH2), and the electrolyte used [Bu4N][ClO4](0.1 M, Fluka, dried under vacuum for 24oC) or [Bu4N][PF6](0.1 M, Fluka, puriss). The measurements were carried out by the device Princeton Applied Research Model 273 Potentiostat/Galvanostat with a computer-controlled "Compudyne 486DX, and curves amperage/voltage were obtained using a two-coordinate recorder Graphtec Model WX1200, or using a voltage regulator/digital comonomer Princeton Applied Research Model 173/179, equipped with IR compensation positive feedback, universal programmer, and a two-coordinate recorder Houston Instruments Model 2000. In some experiments we added ferrocene (Fc) as an internal standard capacity, applicable to conclusions. The formal potentials were calculated as average values of anodic and cathodic peak potentials and compared with NHE. Roselena. Charts peak current depending on the square root of scan rates in the range between 20 and 500 mV-1for all couples were in the nature of linear dependence.

Mass-spectrometry. Spectra electrospray mass spectrometry were obtained using the mass spectrometer Finnigan-MAT SSQ700 (San Jose, CA) equipped with electrospray interface Analytica of Branford. Used voltage elektrorazpredelenie in 2400-3400 C. the Samples were dissolved in either acetonitrile or dichloromethane at concentrations of approximately 10 pmol/μl and injected into intrface ESI before collecting data by direct infusion at a flow rate of 1 ál/min Experiments on mass spectrometry electron impact ionization of positive ions (70 eV) was carried out using a quadrupole mass spectrometer Finnigan-MAT 4615 in combination with the data acquisition system INCOS. The temperature of the ion source was 150oC and the temperature in the chamber with multiple departments was 100oC. Introduction of the samples was made using gaschromatography or by direct insertion of the probe. Spectra in the bombardment of fast atoms (positive ions) was obtained with the help of the device Finnigan MAT 212 in combination with SKN 70oC. Used gun for saddle-shaped field, obtained by ion technology with rapid atoms, and xenon was 8 Kev. As a matrix of fast atom bombardment used diglycerin. Experiments on shock electron ionization of positive ions (70 eV) MS/MS was performed on a tandem quadrupole mass spectrometer Finnigan-MAT TSQ/700. The introduction of the samples was carried out using direct probe introduction. The temperature of the ion source was maintained at 150oC, and in the chamber with multiple offices in the 70oC. Dissociation, caused by the collisions of atoms, obtained by introduction of argon in the center only-RF collision vosmipolosnoy up until the chamber pressure has not reached 0,9-2,510-6Torr. Nominal kinetic energy of ions, which are products of dissociation, caused by the collisions of atoms, was < 35 eV (laboratory data). Data devices with high resolution were obtained using a mass spectrometer with double focusing JEOL JMS AX-505H configuration EB using a resolution of 7500. The introduction of the samples was carried out using a gas chromatograph or probe for direct injection. In the process of obtaining mass spectra performerin centuries of masses performerin. Conditions of GC/MS: the column 20 m x 0.25 mm DB-1701 (J&W Scientific); carrier gas, helium with a linear velocity of 40 cm/sec; injector 125oC; column temperature 35oC for 3 min, then rises with the intensity of 10oC/min to 100oC; injection, separation, approximately in the ratio of 50:1.

Spectroscopic methods: 300 MHz1H NMR spectra and 75 MHz13C NMR spectra were obtained using the device IBM AF300 using a magnetic system Oxford Superconducting, the data collection was controlled by the software Bruker. Infrared spectra were obtained on a spectrometer (Mattson Galaxy Series 5000 FTIR running a Macintosh II. Spectra UV/vis were obtained using the spectrophotometer Hewlett Packard 8452A under computer control Zenith Z - 425/SX. Conventional EPR spectra of the X-band were recorded on a Bruker spectrometer ER300, equipped with a helium cryostat flow Oxford ESR 900. Moessbauer spectra were obtained on devices with constant acceleration, and the isomeric shifts were noted relative to metallic iron as standard at 298 K. in Order to avoid orientation of polycrystalline samples under the action of a magnetic field, the samples suspended in a frozen Noyola (nujole).

Synthesis of diamines that are not manufactured

Example 1
oC. the Mixture is maintained at a temperature below 40oC, but above 10oC by cooling and speed control additives acid. Separated a considerable amount of mononitrovaniya. Stirring is continued and added an additional amount of nitric acid (212,7 ml fuming) (additive produced by drop within 1 hour), while the temperature of the solution was maintained at a level below the 30oC. as was the second narisovanie, monomicrobial dissolved and when you added all the acid, the solution became transparent. The mixture is left for two hours and then poured into about 1.5 l of ice water. Fallen in sediment dinitrosobenzene was filtered, abundantly washed with water to remove acid (pH > 5) and recrystallization directly from the minimum quantity of hot EtOH (600 ml). The yield of 1,2-dimethoxy-4,5-dinitrobenzene was of 69.0 g (87%). Characteristics: temp. melting 129,5-130,5oC. 1H NMR (CDCl3) [ppm] : 7.35 (a), 1535 & 1518 (s, str, ArNO2).Estimates for C8H8N2O6: C, 42.11; H, 3.53; N, 12.28. Found: C, 42.12; H, 3,54; N Of 12.33.

1.2-diamino-4.5 - dimethoxybenzene: 1,2-dimethoxy-4,5-dinitrobenzene (10 g, while 43.8 mmol) was restored to 1,2-dimethoxy-4,5-diaminobenzene in acidic MeOH (175 ml + 2 EQ. inorganic acids (i.e., 10 ml conc. HBr)) by catalytic hydrogenation using 10% Pd/C catalyst (24-36 hours, 20-22 psig H2were absorbed from the reservoir). If at first) was added over 2 EQ. HBr, the activity of Pd/C catalyst was suppressed. After completion of the hydrogenation added another 4-5 EQ. conc. inorganic acid, to protect the material from oxidation by the air and the mixture is evaporated in a rotary evaporator to obtain a red/purple oil. The crude material was purified by addition of a small amount of abs. EtOH6then poured the sludge into 600 ml ice Et2O and left in the freezer overnight.

Red-violet product was collected by filtration, quickly air dried, then stored in a desiccator until the completion of the drying process. Prolonged exposure to salt of the diamine air/water causes become green, which indicates irreversible oxidation. In resultdata dihydrobromide salt):1H NMR (d5pyridine) [ppm]: 10.35 (s, br, 7.5 H, H2O/py.HBr/R-NH2fast exchange), 7.35 (s, 2 H, ArH), 3.60 (s, 6 H, ArOCH3IR (nujol/NaCl) [cm-1: 3085 (br, OH), 2557 (s, str, ArNH3+), 1623 (s, w, asymmetric. NH3+bend/stretch aryl ring), 1539, 1519 (s, m. approx. MH3+the fold). (Estimates for C8H12N2O2) (HBr)2, (H2O)0,66. (C, 28.09; H, 4.52: N, 8.19. Found: C, 27.82; H, 4.18; N, 8.37. Independent confirmation of hydrogenation was obtained from the results of IR and NMR spectroscopy.

Anhydrous sulfate salt of 1,2-diamino-4,5-dimethoxybenzene was described by Nakamura, M. et al. in "Fluorimetric Determination of Aromatic Aldehydes with 4,5 - Dimethoxy-l,2-Diaminobenzene". Anal.Chim. Acta. (1982), 134, p.39-45: 1,2-diamino-4,5-dimethoxybenzene (2 g) was dissolved in EtOH (20 ml) and was mixed with H2SO4(conc., about 2 ml). Product recrystallization from EtOH, receiving almost colorless needles (yield about 2 g). Estimates for C8H14O6N2S: C, 36.1; H, 5.3; N, 10.5. Found: C, 35.85; H, 5.6; 20 N, 10.4.

B. Getting 1.2-diamino-4-acetamidobenzoyl of 1.4-diamino-2-nitrobenzene (2-nitro-1.4-phenylenediamine).

1-amino-2-nitro-4-acetamidobenzoyl: 1,4 - diamino-2-nitrobenzene (2-nitro-1,4 - phenylenediamine) selectively azetilirovanny from the meta to the nitro group is easily subjected to acetylation using acetic anhydride in acetone (amino group from ortho to nitroisoquinoline). Output 1-amino-2-nitro-4 - acetamidobenzoyl (2-nitro-4-acetamidophenyl) was > 90%. Features:1H NMR (CD3OD) [ppm]: 8,3 (m, 1 H, ArH), 7.5 (M, 1H, ArH), 6.9 (M, 1H, ArH), 2.1 (s, 3H, acetyl CH3that agrees well with McFarlane. IR (nujol/NaCl) [cm-1] : 3470 (s, str, HOAc), 3340 - 3150(m, m/str, ndimethylacetamide ArNH + ArMH2), 1661 (s, str, ndimethylacetamide CO), 1643 (s, str, H associated ndimethylacetamide CO), 1592 (s, m/w, stretching.Arilyn.), 1547 (s, str, ArNO2,) & 1512 (s, m ArNO2). Anal. (Dried at 80oC) Calculated data for: C8H9N3O3; C, 49.23; H, 4.65; N, 21.53. Found: C, At 49.36; H, 4.55; N, 21.31.

1.2-diamino-4-acetamidobenzoyl: 1-amino-2-nitro-4-acetamidobenzoyl restored to 1,2-diamino-4-acetamidobenzoyl in acetic acid (HOAc)/MeOH, using catalytic hydrogenation with 10% Pd/C catalyst. The material was isolated as dihydrochloride salt. Yield > 90%. Features:

1H NMR (CD3OD) [ppm]: 6.94 (t, 1 H, ArH), 6.68 (t, 1 H, ArH), 6.62 (t, 1 H, ArH), 2.1

(s, 3H, acetyl CH3). IR (nujol/NaCl) [cm-1]: 3348 (s, str, ndimethylacetamide ArNH), 3226 - 3100

(m, m, ArNH2), 2588 (s,br, str, ArNH3+), 1649 (s, str, ndimethylacetamide CO), 1623 (s, str, H - linked ndimethylacetamide CO). Anal. (Dried at 80oC) estimates for C8H13N3OCl2. (HCl/H2O)a 0.1: C, 39.45; H, 5.50; N, 17.25; Cl, 30,57. Found: C, Pasha of 36.5-38% HCl, used to obtain cleaners containing hydrochloride salt.

C. Obtaining 2.4-diamino-2.4-dimethylpentane from 2.4-dimethylpentane.

2.4-dibromo-2.4-dimethylpentane: 2.4-dimethylpentane (85 ml, and 68.5 g of 0.60 mol) in

CCl4or 1,2-dichloroethane (1 l) was added N-bromosuccinimide (NBS, 240 g, 1.35 mol,

of 2.26 equiv.). The mixture was heated under reflux was added benzoyl peroxide (20 mg). While the solution was heated under reflux (24 hours), light orange solid (succinimide) pop up to the surface of a halogenated solvent, while the unreacted N-bromosuccinimide remained at the bottom. Benzoyl peroxide several times was added to the mixture during the distillation (about 20 mg; 12-24 hour intervals) until such time as no N-bromosuccinimide will not be seen, usually, the reaction was terminated after 24 hours. When the reaction was completed, the solid was collected by filtration and passed to waste, halogenated solvent/Br2was removed from the mother liquor under reduced pressure, obtaining a light yellow oil. To remove residual halogenated solvent was added 95% EtOH (100 ml), the solvent was again removed under reduced pressure, and obtained slightly yellow s, str, CH), 2858 (s, w, CH), 1701 (s, str, ketone CO).

2.4-diazido-2.4-dimethylpentane: a Solution of 2,4-dibromo-2,4 - dimethylpentane received as described above or purchased from a company Lancaster Synthesis (89,8 g, 0.33 mol) in EtOH (1.2 l, 95%) was added to a solution of NaN3(Attention! to 47.2 g, 0,726 mol, 2.2 equiv.) in water (0.6 l). The solution was heated under reflux (16 h) to obtain a light orange solution. EtOH was removed under reduced pressure until, until the solution became turbid. Muddy water solution three times were extracted, still warm, pentane (500 ml), and combined extracts were dried over Na2SO4and concentrated to 300 ml under reduced pressure. Then was added glacial acetic acid (100 ml) and the remaining pentane was removed under reduced pressure. This processing is needed to remove excess NaN3because the product the next step is subjected to Pd/C and avoid the formation of azides of heavy metals (because of the danger of explosion). The solvent was removed from a small sample under reduced pressure to obtain pure oil (< 20 mg) that were used to conduct spectroscopy:1H NMR (CDCl3):1,54 (s). IR (net.) [cm-1]: 2115 (RN3), 1720 (ketone CO). It should be taken into account, Job, never stand out in a concentrated form or in the form of solid substances in quantities greater than 20 mg.

2.4-diamino-2.4-dimethylpentan-3 - one: glacial acetic acid (50 ml) was added HOAc solution dialkylated obtained in the previous step, and this solution was added 10% Pd/C (2,7 r). The mixture was first made at a pressure of 50 pounds per square inch (344,738 kPa) (1 week) in the hydrogenerator Parra. Since during the reaction at each of the absorbed molecule H2it turns out one molecule of N2the bomb was recovered and reused 10 times increased pressure H2up to 50 psig (344,738 kPa). (H2from a reservoir of high pressure is not effectively absorbed). The charcoal was removed by filtration, and HOAc was removed under reduced pressure. After the addition of HBr (48%, 76 ml) and the mixture was dissolved in EtOH. Volatile compounds were removed under reduced pressure to obtain a solid reddish-brown substance, which was washed with a mixture (200 ml), THF (50%(, EtOH (45%), and conc. HBr (5%), or a mixture of THF (95%) and conc. HBr (5%). The obtained white powder was dihydrobromide salt of 2,4-diamino-2,4 - dimethylpentan- -it (56,2 g, 48% from 2,4-dibromo-2,4 - dimethylpentane). Additional product can be collected from the wash water, which is drained from several in order to protect amines from oxidative degradation.

Features:1H NMR(CDCl3/DMSO-d6) 2,4-diamino-2,4-dimethylpentan-3-one. 2 HBr: at 8.62 (6H, s, br. MH3), 1.77 (12 H, s, Me). IR (free base, nujol mull) [cm-1: 3460-3160 (RNH2), 1690 (ketone CO). Anal. (Dried at 80oC). Estimates for C7H16N2O.(HBr)2: C, 27.47; H, 5.93; N, 9.15; Br, 52.22. Found C, 27.43; H, 5.91; N, 9. 11;Br, 52.46.

Synthesis macrocyclization tetraamido-N-donor ligands

Example 2

Synthesis microlensing intermediate (A-L-A)- methylalanine and dimethylmorpholine (tetramethylbiphenyl-substituted intermediate connection).

Hexamethylene intermediate compound (NM)

Put dvuhgolosy flask (1 l) equipped with a funnel, which allows you to balance the pressure (250 ml), and the partition into the atmosphere N2. Add -aminoadamantane acid (i.e., methylalanine) (vs. 20.62 g, 0.2 mol) and dry pyridine (250 ml), dried over sieves 4 a mol) into the flask and heated to 55-65oC under stirring, then add diethylaluminiumchloride (17,8 ml, is 0.135 mol), dissolved in dry pyridine (100 ml, dried over sieves 4 a mol)into the funnel.

Add the contents of the funnel (drop by drop, 1 hour) in the reaction mixture and leave the mixture for the implementation is completed, the reaction is stopped by adding H2O (30 ml) under stirring (60-70oC, 24 hours).

Reduce the volume of solvent by evaporation on a rotary evaporator to obtain the oil, then add HCl (conc., about 25 ml) to a final pH value of 2-3. Put the hot solution in a refrigerator (4oC, 15 h.) and collect the product by filtration on a Frit, and washed thoroughly with acetonitrile (CH ml). Air-dried, white product (16,5 -19,8 g, yield 45-60%) should be stored in executor. This product is usually pure enough for was the reaction of the closing of the rings, but sometimes may require recrystallization. Features:1H NMR (d5pyridine, [ppm] ); 9/2-9.8 br s, 2H (carboxyls. OH), 8.23 s, 2H (amide), 1.87 s 12H (CH3), 1.74 s 6H (CH3). IR(nujol/NaCl) [cm-1]: 3317.0 (amide NH); 1717.9 (carboxyls. CO); 1625.7 (amide CO). Anal. (dried at 100oC). Raschet. data for C13H22N2O6: C 51.63, H 7.34.N 9.27. The detection.: C 51.64, H 7.35, N 9.33.

Example 3

Large-scale synthesis microlensing intermediate substance of methylalanine and diethyltoluenediamine (TETRAMETHYLBUTYL-substituted intermediate connection)

If you want to carry out large-scale synthesis, the flask is placed in an atmosphere of N2. Add-aminoadamantane acid (i.e., methylalanine) (90,3 g, 0.9 mol)(or any described above or amino), through a tube injected anhydrous pyridine (1.4 l, sure seal) into the flask and heated to 45 - 55oC under stirring, Through a tube introduced pyridine (100 ml, sure seal), and then diethylaluminiumchloride (104,4 ml, 0.61 mol) in the funnel. Add the contents of the funnel (one drop at a time, 3-4 hours) in the reaction mixture, remove the funnel, leave the flask to effect the acylation of (55-65oC, 120-130 hours) in an atmosphere of N2. After the acylation is complete, the reaction is stopped by adding H2O (100 ml) under stirring (60-70oC, 24-36 hours). Reduce the volume of solvent by evaporation on a rotary evaporator to obtain the oil, then add HCl (conc., about 110 ml) to a final pH value of 2-3. Put the hot solution in a refrigerator (4oC, 15 h. and collect the product by filtration on a Frit, and washed thoroughly with acetonitrile (700 ml, 150 ml) under stirring in an Erlenmeyer flask. Pounded the air-dried white product (87,9 g, yield 60%) in a mortar and stored in a desiccator. The intermediate amide compound found in the large-scale reaction, before use in the reaction closure rings, with alternova intermediate compounds.

The crude intermediate compound from Example 2 or 3 (of 50.4 g, 0,153 mol) in H2O (a little less than 500 ml, deionizers.) dissolve by adding Na2CO3(16.2 g, 0,153 mol) in three parts, the additive is produced slowly and carefully, to avoid excessive foaming. Stir very slowly, and heat gradually. The solution is brought to a boil, filtered and acidified with HCl (conc., 30 ml, 0.36 mol). Leave the solution to cool (overnight, 4oC), then the precipitate is filtered off and washed with acetonitrile (250 ml). Product, dried air (38,8 of 45.4 g, yield 77-90%) should be stored in a desiccator.

Reaction microcrystallization.

Developed several ways of synthesis for the preparation of macrocyclic tetraaminobiphenyl. The method is based on organic azides described in Uffelman, E. S. , Ph.D. Thesis, California Institute of Technology (1992) and Kostka, K. L, Ph.D. Thesis, Carnegie Mellon University (1993). Examples of several ways of synthesis for the preparation of macrocyclic tetraaminodiphenyl when using a new method of synthesis is shown below.

Join trichloride phosphorus.

How PCl3join amide intermediate reaction product to an aromatic 1,2 - diamines allows you to safely and de is Ianto method PCl3accession, the differences between them relate to sequence the introduction of additives to the choice of reagents. These methods can be used to obtain a wide variety of different compounds with different substituents at the level of electrons present on the bridge diamine, or with spatial substituents present in the amide intermediate compound, mainly because of the parallel connection amide derivatives microlensing type in all kinds of synthesis.

Example 5

A. Synthesis of macrocyclic compounds by PCl3connection.

In a flask with a long neck (250 ml) is placed amide intermediate compound from Examples 2-4 (10 mmol) and a stir bar, and then the flask was calcined in a furnace (80-100oC, 30 - 45 min). Hot flask in an atmosphere of N2add erillinen (10 mmol) and anhydrous pyridine (50 ml, sure seal). The flask is heated (50-60oC) via syringe inject PCl3(d=1.574 g/ml, 1,72 ml, 20 mmol); injection produce as quickly as possible without distillation. Is exothermic reaction, so you should take precautions. Then the temperature was raised to a temperature of distillation or slightly below it (100 - 115oC) ostavlayi acidified with HCl (1 EQ., about 60 ml) to a final value . The mixture moving in the Erlenmeyer flask (for flushing the flask using water) and stirred with CH2Cl2(300 ml, 2-3 hours), then extracted with additional CH2Cl2(2 x 150 ml). The combined organic layers are washed with dilute HCl (0.1 M, h ml) and then diluted aqueous Na2CO3(2 x 5 g/100 ml). Organic solvents are removed on a rotary evaporator to obtain the crude product (30%). Weight of the crude product is usually equivalent to the initial weight of the diamine.

B. Synthesis of macrocyclic compounds by PCl3joining

In a flask with a long neck (250 ml) were placed MgSO4(5 g), mixer, erillinen (10 mmol) and 50 ml of pyridine (dried over sieves 4 a mol) was then placed in an atmosphere of N2. After the syringe was added PCl3(d=1.754 g/ml, 1,72 ml, 20 mmol) and the mixture was distilled for 30 min, before the formation of an orange-yellow precipitate. Then the mixture is slightly cooled, was added amide intermediate compound (10 mmol), after which the mixture was distilled in an atmosphere of N2(115oC, 48 hours). After completion of the acylation of the contents of the flask was acidified with HCl (1 EQ., about 60 ml) to a final pH of 2. The mixture was transferred in iCustom CH2Cl2(2 x 150 ml). The combined organic layers are washed with dilute HCl (0.1 M, h ml) and then diluted aqueous Na2CO3(2x5 g/100 ml). Organic solvents are removed on a rotary evaporator to obtain the crude product (30%). Weight of the crude product is usually equivalent to the initial weight of the diamine.

Note: for large-scale reactions macrocyclization time interaction was increased to 4-5 days when the distillation of the mixture, and most of the pyridine present in the end of the interaction was removed using a rotary evaporator before acidification.

Example 6

Getting HEXAMETHYL-dichlorobenzene from hexamethylene intermediate + dichlorobenzidine 1.2-diamino-4.5 - dichlorobenzene (1.77 g, 10 mmol) was used as the diamine with hexamethylene intermediate connection (to 3.02 g, 10 mmol) in PCl3method A or B the reaction of macrocyclization. The crude macrocyclic compound (1,33 g, 30%) recrystallization minimum number of hot n - propanol by evaporation. After the first recrystallization was obtained a yield of 60%. Features:1H NMR [ppm] : 7.69 (s, 2H, ArH), 7.39 (s, 2H, amide NH), (s, 2H, amide NH), 1.58 (s, 12H, methyl otitle (sh, m, amide NH), 3338 (s, str, amide NH), 1689 (s, str, amide CO), 1643 (s, str, amide CO). Analysis. Raschet. data for C19H24N4O4Cl2(C3H8O)of 0.2: C, 51.70; H, 5.57, N 12.30%. Found C, 51.69; H, 5.63; N, 12.33%.

The reactions proceed through oxazalone

Oxazalone accession amide intermediate compounds to aromatic diamines also allows to obtain macrocyclic tetraamide safe and cheap way, and the reaction product yield will be high, but there is less sensitive to additional functional groups. The macrocycles that can occur through PCl3joining, can also be obtained by joining through oxazalone. In addition, lower sensitivity to additional functional groups allows you to get ligands with additional functional groups that impart new properties of the obtained complex compounds of metals. Specific examples include the introduction of reactive groups (such as amine or vinyl), attached as addenda to the aryl ring of the macrocycle, which allows covalent joining prior macrocycles to some model of the way.

In a flask with a long neck (250 ml) were placed amide intermediate compound (3.3 g, 10 mmol), a stir bar, and then the flask was progulivali in the oven (80-100oC, 30 - 45 min). Hot flask was equipped with a septum and placed in an atmosphere of N2. Through a tube introduced anhydrous pyridine (50 ml, sure seal) and continued heating, adding at the same time through a syringe trimethylacetylchloride (i.e. pivaloyloxy) (22-24 mmol). The temperature is raised to distillation or slightly below the temperature distillation (110-115oC) and allowing the reaction to proceed in an atmosphere of N2(22-26 hours), while carefully avoiding contamination by the products of other reactions with N2. The reaction mixture changes color from transparent light yellow to yellow-brown. After education oxazalone ends (note:*Pumping an equal number and re-dissolved in dry d5pyridine was allowed to obtain the dominant view (> 80% bis-oxazoline after 24 h of distillation), with the following characteristics: 1H NMR (d [ppm] : 2,10 (q.4H, methylene CH2's) to 1.38 (s, 12H, RCH3) to 0.85 (t, 6H, ethyl CH3's). After the addition of water in the sample for NMR, restored normal range for amide intermediate connection after about 20 hours at RT), add through the tube with a big hole, either in the form of a solution in anhydrous pyridine (sure seal), which in an atmosphere of N2allocated gases, if the limitations imposed by the solubility and availability of space in the upper part of the flask, allow you to do this. The reaction of the closing of the rings is the distillation in the next 48-72 hours (the longer the interaction will be required for large-scale reactions) in an atmosphere of N2without mutual contamination by the products of other reactions. The mixture is usually black and brown. After the acylation is complete, the reaction is stopped by addition of H2O (30 ml) and stirred at distillation (100oC, 22-26 hours). The mixture is cooled and move into the flask with a round bottom (500 ml) using the minimum number of H2O to flush dinagalu flask. The solvent is removed by rotary evaporator to obtain a mixture of the crude product in the form of oil is reddish-brown or black-brown solid. It should be noted that if the functional group, the mixture of the crude product can be dissolved in CH2Cl2and it can be washed with dilute aqueous HCl and dilute aqueous Na2CO3. The removal of organic solvent etc which were suitable for immediate recrystallization, as a result of pure macrocyclic compound.

Example 8

Getting TMDE-AcB of TETRAMETHYLBUTYL - intermediate + ASV diamine through oxazalone.

This macrocyclic compound is a protected form macrocyclic compounds containing more amino groups, which can be attached to various media due to the formation of amide bond between the base and an additional amino group. Due to the formation of undesirable hydrogen bonds (as suggested) the response of the closed rings requires a long distillation, in order to achieve the formation of macrocycles, 1,2-diamino-4 - acetamidobenzoyl-dihydrochloride (9 mmol) was used as the diamine in the reaction closing oxazalone rings. Time macrocyclization increased (distillation 5 days), after which the reaction was stopped in the usual way and spent acid - core processing to obtain a mixture triamide compounds containing macrocyclic imidazole, and the desired tetraamide macrocyclic compounds. Further purification was carried out using chromatography on silica gel (1 >> x 4-5 >>), using acetonitrile in quality is Nola, chloroform or dichloroethane. The output of the diamine was 15-20%. Features:1H NMR (CD3CN) [ppm]): 8.31 (s, 1H, arylacetamide NH), 7.72 (m, 1H, ArH), 7.55 (s, 1H, arylamide NH), 7.44 (s, 1H, arylamide NH), 7.30 (m, 2H, ArH), 6.86 (s, 2H, alkylated NH), 2.05 (q, 4H, ethyl CH2's), 2.01 (s, 3H, acetyl CH3, 1.49 (d, 12H, RCH3's), 0.82 (1, 6H, ethyl CH3's). IR (nujol/NaCl) [cm-1]: 3368 (s, m, amide NH), 3319 (s, m, amide NH), 3291 (sh, m, amide NH), 3268 (s, str, amide NH), 1678 (sh, m, amide CO), 1667 (s, str, amide CO), 1656 (s, str, amide CO), 1639 (sh, m, amide CO), 1608 (s, m, aryl ring/amide). Anal. raschet. data for C23H33N5O5: (H2O)1,25: C, 57.31 H, 7.42 N, 14.53 Found: C, 57.02; H, 7.15; N, 14.33. The presence of MES H2O confirmed 1H NMR and IR.

Example 9

Synthesis parallelomania macrocyclic compounds (MAC*or tetramethylbiphenyl - dimethylpentane of tetradecyltrimethyl intermediate + 2.4-diamino-2.4-dimethyl-pentane-3-one (DMP) through oxazalone

PCl3the way to get H4[MAC*](TETRAMETHYLBUTYL of dimethylpentane) did not allow to obtain an acceptable number of macrocyclic compounds; suggested that this is caused by the formation of undesirable complex between functional group diaminoethane and phosphate reagent. In otlis*] is a method that uses the homogeneous solution, which simplifies the application of diagnostic techniques, such as1H NMR, to determine the reasons for the failure of synthesis. Interaction tetramethylbiphenyl-bis-oxazoline with dimethylpentan-diamine in dry pyridine is not possible to obtain amides (by NMR analysis). Because occasionaly way insensitive to the ketone functional groups, the failure to obtain amides attributed due to the formation of salts of acids on alkylamino functional group, and alkylamino 3-4 pKaunits more alkaline than pyridine, while ariginine matter pKaclose to the pyridine. Therefore, a more alkaline high-boiling solvent (triethylamine, Tripropylamine, diethylaniline) can be used to increase the amount of the resulting amide. For aminobenzoic solvents in the presence of water and amine contaminants causes problems, due to the low solubility of the reactants. Additive Lisovoy acid as a drying agent is of great benefit. Visible output H4[MAC*] you can get (unoptimized yield macrocyclic compound is 2-3%) as a result of interaction (stage 1) tetrame is and should be carried out by fractional recrystallization from toluene in combination with1H NMR.

Most high output H4[MAC*] alkylamine by the known method Uffelman (4 stages of alkylamine) is 8-10%. Visible output4[MAC*] you can get through oxazalone way.

Synthesis of chelate complexes

Connections under the numbers 2, 3, 4 and 5 the following examples are dimethyl copies of the compounds according to Fig. 6.

Example 10.

[Et4N] 2 and [Et4N]3. [tetraethylammonium salt chloro tetramethylbiphenyl-dichlorobenzene-monoanion iron(III) and akvo - tetramethylbiphenyl-dichlorobenzene-monoanion iron (III), respectively.

Source macrocyclic tetraamide on any of the following examples (525 mg, 1.1 mmol) dissolved in tetrahydrofuran (40 ml, Aldrich) in an atmosphere of N2. Tert-utility in the atmosphere N2(2.6 ml, 4.4 mmol, 1.7 M 2.4-dimethylpentane, Aldrich) is added to the solution in an atmosphere of N2when -108oC. Add the ferric chloride (anhydrous, 155 mg, 1.2 mmol, Alfa) and the solution warmed to room temperature with stirring (16 hours) to obtain a precipitate, is sensitive to air complex compounds of FeIIL. Through the drying tube leak air (2 hours) nom pressure. Output: 595 mg (about 93%). Due to the different solutionone and limited solubility of the lithium salt to be converted to tetraethylammonium salt for later use. Lithium salt (595 mg) in CH3OH (50 ml) is placed in an ion-exchange column of DowexH-100, 25 g, 2 cm x 12.5 cm), which is pre-saturated with cations [Et4N]+and the band elute CH3OH (100 ml). The solvent is removed under reduced pressure. The residue is suspended in CH2Cl2(20 ml) and the mixture filtered. The solvent is removed from the mother liquor under reduced pressure to obtain a hygroscopic glassy residue [Et4N] 2, which can be used without further purification. IR (nujol/NaCl, cm-1): 1619 (CO)amide), 1575 (CO)amide), 1534 (CO)amide). Thorough cleaning of the source material iron (III) it is most convenient to carry out by means of axial aquatuning complex, and not by means of this axial hardening complex. [Et4N]2 (550 mg, about 0.7 mmol) was dissolved in CH3CN (2 ml) and was added into the solution, which was stirred (1 hour). The precipitated AgCl was filtered and the solvent evaporated under reduced pressure. Received [Et4N]3 was further purified, elwira through the columns of sofyali of H2O.

Example 11

[Et4N] (tetraethylammonium salt chloro - tetramethylbiphenyl-dichlorobenzene-monoanion iron (IV)

[Et4N]2 (500 mg, about 0.6 mmol) was dissolved in CH2Cl2(30 ml). To the solution was added nitrate ammoniuria (IV) (10.3 g, and 18.3 mmol) and the mixture was stirred for 2 hours. Solid cerium salt was removed by filtration. Received the product by removal of the solvent under reduced pressure and drying under vacuum.

Example 12

Synthesis of [Ph4P] 5[tetraphenylphosphonium salt cyano - tetramethylbiphenyl-dichlorobenzene-monoanion iron (IV)

[Et4N] 4 (tetraethylammonium salt chloro-tetramethylbiphenyl-dichlorobenzene-monoanion iron (IV)) (225 mg, 0.33 mmol) is suspended in H2O (10 ml). Sodium cyanide (140 mg, 2,85 mmol) was dissolved in H2O (10 ml) and added to the suspension, after which the mixture was subjected to ultrasonic treatment (Branson 1200, 0.5 hours). Then the mixture was filtered and caused the precipitation of a blue reaction product with the help of supplements PPh4Cl [tetraphenylphosphonium], dissolved in water (600 ml, 1.6 mmol, 10 ml, Aldrich). The precipitate was collected and washed2O (2x10 ml). The material must be extracted from silica gel using CH3CN: CH2Cl2(1:1,60 ml). Dissolve is where it is refuelled pentane (150 ml) was obtained powder (90 mg, 0.10 mmol).

Example 13

Synthesis of [Ph4P] 5[tetraphenylphosphonium salt of iron (IV) cyano-tetramethylbiphenyl-dichlorobenzene-monoanion] from source materials containing nitrilase.

[Ph4] 5[tetraphenylphosphonium salt of iron (IV) cyano-tetramethylbiphenyl-dichlorobenzene monoanion] can be obtained in the presence of a base or without. In the absence of base color disappears as the solvent is removed during processing. Therefore, the selection of the product to obtain a solid substance is best done in the presence of added base at a pH in the range of 9-10. The following reaction will get 5 when using each of CH3CN, CD3CN,CH3CH2CN and (CH3)2CHCN as solvent environment. The basis of the above reaction medium is added.

Example 14

Synthesis of [Ph4P]5 in the presence of a base.

[Et4N] 3 (160 mg, 0.23 mmol) is dissolved in the selected nitrile solvent (6 ml). Cm. Example 13. Add tetraethylammonium hydroxide as the base (20 wt.%, 0,370 ml, 0.52 mmol, Aldrich), then tert - butylhydroperoxide (90%, 0,605 ml, 5.4 mmol, Aldrich), produce additive drop by drop in peremeci is the learn of oil sludge which was dissolved in H2O (15 ml) and filtered. The material is then precipitated from the filtrate by adding aqueous solution of PPh4Cl (800 mg, 2.1 mmol, Aldrich, 10 ml). The blue precipitate is collected and washed with H2O (2x10 ml). Yield: 130 mg, 0.15 mmol (65%). Subsequent purification was performed as described in [Ph4P]5, Example 12.

Example 15

1-[2-((E)-2-butenyl-2-ethylamino)- 2-methylpropanamide] -2-[5.5-dimethylhydantoin]-4.5-dichlorobenzene (i.e., the product of decomposition of the ligand)

[Et4N] 2 (130 mg, 0.13 mmol) dissolved in CH3CN (5 ml, Aldrich). Slowly (over 3 minutes) add 90% solution of tert-butylhydroperoxide (0,445 ml, 4 mmol, Aldrich). The reaction mixture was stirred (25 min) and then all the liquid is removed under reduced pressure. The residue is dissolved in CH2Cl2and then loaded onto the plate for thin-layer preparative chromatography (TLC) (Silica gel GF, 1000 mm, 20 cm x 20 cm) and elute with a mixture of solvents 15% CH3CN/85% CH2Cl2. The band encountered when UV irradiation with Rf 0.3. Part of the silica containing the product is removed from the plate, and the product is extracting CH2Cl2:CH3CN (1:1). The solution is filtered and the solvent is removed under reduced pressure. Solid particles get PU is t by filtration and washed with pentane (2x10 ml).

Some examples of specific embodiments of the invention, i.e., macrocyclic compounds according to the invention disclosed in application for U.S. patent N 08/684670 in the name of T. Collins et al., entitled "Metal Ligand Containing Bleaching Compositions".

1. The complex compound containing macrocyclic tetradentate ligand having the structure:

< / BR>
where R1and R2have the same or different values are related or unrelated, and each is selected from the group consisting of hydrogen, halogen, methyl, CF3and, if they are connected, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl are spatial dull and conformationally difficult, so that the oxidative degradation of complex metal compound is limited, when the complex is in the presence of an oxidizing environment;

Z represents a stable to oxidation atom, which metallocomplexes selected from the group consisting of nitrogen and oxygen;

X represents an oxidation resistant functional group selected from O or NRswhere Rsrepresents a methyl, phenyl, hydroxyl, auxillou group, CF3or CH2CF3;

R3is a FR is>in pairs and as a group have the same or different values and each is selected from the group consisting of alkyl, phenyl, halogen and CF3;

R4is a piece that connects the adjacent Z atoms, containing

< / BR>
or

< / BR>
where R10, R11, R12and R13in pairs and as a group have the same or different values and each is selected from the group consisting of alkyl, phenyl, halogen and CF3;

R5is a piece that connects the adjacent Z atoms selected from the group consisting of: (i)

< / BR>
and

< / BR>
where R14, R15, R16and R17have the same or different values and each represents alkyl, phenyl, halogen or CF3,

and (ii) mono-, di-, tri - and Tetra-substituted aryl and heteroaryl substituents containing

< / BR>
< / BR>
< / BR>
< / BR>
where each Y is the same or different values and contains halogen, hydrogen, alkyl, phenyl, amino, substituted amino, nitro, alkoxy, phenyloxy and combinations thereof.

2. Connection on p. 1, in which at least three atoms Z represent nitrogen.

3. Chelate complex of the formula

< / BR>
where M represents a transition metal is 1 Ch2and Ch3are resistant to oxidation chelating agents that have the same or different values and which form a 5 - or 6-membered ring with the specified metal, and Ch1is a fragment of a connecting neighboring atoms, Z is selected from the group consisting of: (i)

< / BR>
and

< / BR>
where R14, R15, R16and R17have the same or different values and each represents alkyl, phenyl, halogen or CF3,

and (ii) mono-, di-, tri - and Tetra-substituted aryl and heteroaryl substituents containing

< / BR>
< / BR>
< / BR>
< / BR>
where each Y is the same or different values and contain halogen, hydrogen, alkyl, phenyl, amino, substituted amino, nitro, alkoxy, phenyloxy and their combinations;

Ch2is a piece that connects the adjacent Z atoms, containing

< / BR>
or

< / BR>
where R6, R7, R8and R9in pairs or collectively have the same or different values and each is selected from the group consisting of alkyl, phenyl, halogen and CF3;

Ch3is a piece that connects the adjacent Z atoms, containing

< / BR>
or

< / BR>
where R10, R11the dust, consisting of alkyl, phenyl, halogen and CF3;

Ch4represents a chelating group of the formula

< / BR>
where R1and R2have the same or different values are related or unrelated, and each is selected from the group consisting of hydrogen, halogen, methyl, CF3and, if they are connected, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl are spatial dull and conformationally difficult, so that the oxidative degradation of complex metal compound is limited, when the complex is in the presence of an oxidizing environment.

4. Chelate complex on p. 3, in which a transition metal of group VIII of the Periodic table is selected from the group including Fe, Co, Ni, Ru, Rh, Pd, Os, Ir, Pt.

5. Complex on p. 3, further comprises at least one ligand that is associated with M

6. Complex on p. 3, in which Ch1represents an integral part selected from the group consisting of C6H2Y2C6H3Y1C6Y4C5H3N or where Y represents halogen, hydrogen, alkyl, CH3, NH2or SNO, and R10and R11have the same or different values and each before the SUB>2joined so that they form together with the cyclic carbon to which they are both linked five-membered ring.

8. Complex p. 3 in which R1and R2joined so that they form together with the cyclic carbon to which they are both linked six-membered ring.

9. Complex on p. 3, wherein said at least one ligand is a Deputy containing oxygen.

10. Complex p. 9, wherein said at least one ligand is selected from the group consisting of peroxide, HE2About him.

11. Intermediate compound for the production of complex compounds containing macrocyclic tetradentate ligand, p. 1, containing the structure

< / BR>
where Z represents a stable to oxidation atom, which metallocomplexes selected from the group consisting of nitrogen and oxygen;

R1and R2have the same or different values are related or unrelated, and each is selected from the group consisting of hydrogen, halogen, methyl, CF3and, if they are connected, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl are spatial dull, confirmatio the degradation, when the intermediate compound is in the presence of an oxidizing environment;

X represents an oxidation resistant functional group selected from O or NRswhere Rsis methyl, phenyl, hydroxyl, axilla group, CF3or CH2CF3;

R3is a piece that connects the adjacent Z atoms, containing

< / BR>
or

< / BR>
where R6, R7, R8and R9in pairs and as a group have the same or different values and each is selected from the group consisting of alkyl, phenyl, hydrogen, halogen, halogenated Akilov, halogenated arrow and CF3;

R4is a fragment of a connecting adjacent Z atoms, containing

< / BR>
or

< / BR>
where R10, R11, R12and R13in pairs and as a group have the same or different values and each is selected from the group consisting of alkyl, phenyl, hydrogen, halogen, halogenated Akilov, halogenated arrow and CF3.

 

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