Urea residues

Fig. 10 Chiral Calix[4]arene tetraurea unit bearing stereogenic centers on the urea residues...

Fig. 19 Achiral calix[4]arenes with different substituents on the urea residues lead to diastereoisomeric chiral dimeric capsules...

Scheme 5.9 Synthesis of tetra-urea calix[4]arenes bearing two different urea residues in the sequence ABAB (a) and AABB (b), using the protection of amino functions by trityl- or Boc-groups. (Y = C5Hln).

The structure of the capsule, proposed initially on the basis of these NMR-data, was completely confirmed by the first single crystal X-ray structure (Figure 5.2) [34]. The two calix[4]arenes are connected via their wide rims by a seam of intermolecular hydrogen bonds alternatingly involving the urea residues of both calixarenes. The directionality of this hydrogen bonded belt is the reason for the inequivalence of the two aromatic protons of a given phenolic unit mentioned above. 

A and B just characterize different phenolic units, where the difference may be due to the ether residues Y or to the urea residues R or both. 

In spite of the similar distance (13.4 A vs. 12.3 A), the different orientation of the urea residues of the two calixarenes could allow a selective connection of functional groups attached to the same calixarene. In the following we will name such a reaction /-connection to distiguish it from a (1-connection taking place between functional groups belonging to different calixarenes. 

The olefin metathesis between alkenyl groups has been frequently used in recent years to stabilize molecules (e.g., dendrimers [46]) or molecular assemblies [47] by additional covalent connectivities [48] and to synthesize macrocydes or more demanding structures like multiple catenanes [24]. Therefore, this reaction was chosen for the connection of alkenyl residues attached to a calix[4]arene via the urea residues. To avoid complications by ds/trans isomerism around the newly formed double bond, the crude reaction mixture was always hydrogenated before working up (Scheme 5.10). 

To obtain selectively a single, well-defined product, it is obviously not sufficient to arrange the reacting groups in an appropriate mutual position. A perfect preorganization also demands the separation of those functional groups which should not be involved in the reaction. For an intramolecular connection between reactive functions attached to the urea residues, this preorganization is possible in heterodimers with a non-reactive tetra-urea calix[4]arene. 

Even in this case, the yield of pure 10 is surprisingly high (70-75%), although one undesired connection is possible between the two monoalkenyl urea residues. 

Molecular models suggest that such a P -connection between remote alkenyl residues in a dimer is possible. To check whether it really occurs under the conditions of the metathesis reaction, we synthesized the monoloop tetra-urea compounds 16, in which one of the non-cyclic urea residues is substituted by a bulky group which cannot penetrate the loop (Scheme 5.18). (The synthesis is analogous to that of 15, introducing in the final two steps the bulky residue first.). 

Formally compound 16 belongs to the AABC-type of tetra-ureas (compare Section 5.3.2) for which numerous regioisomeric dimers are possible. However, these substituents at the urea residues ensure that selectively only one dimer is formed, in which no overlap of the loops occurs and no penetration of the loop by the bulky group takes place. NMR spectra are in agreement with the formation of a single C2-symmetrical dimer, which is necessarily composed of the same enantiomer of 16. 

The preorganization of functional groups attached to the urea residues could also be used for the synthesis of multiple rotaxanes. Schematically, this is shown for tetra[2] rotaxanes in Scheme 5.20. Bis[2]rotaxanes will be available analogously, using a bisloop compound 8 instead of the tetraloop compound 9. 

Scheme 5.23 Self-sorting of open (1), monoloop (15 with tolyl urea residues), and bisloop (8) tetra-ureas. The addition of bisloop compound 8 converts the mixture of three dimers 1-1, 1-15, and 15-15 into a mixture of only two dimers, 1 -8 and 15-15, the only possibility to have all tetra-ureas assembled in a dimer.

For derivatives with chiral urea residues see Section 7.2. 

If additionally chiral centers (e.g. asymmetric C-atoms, characterized here by D and L) are incorporated into the ether or urea residues two diastereomeric forms of this single tetraurea LA (LAP, LAM) are possible in a dimer due to the orientation of the carbonyl groups (indicated by P and M). Both forms must be present in a homodimer of such a tetraurea and for a heterodimer formed with a normal tetraurea B two diastereomeric forms (LAP-BM, LAM-BP) should exist. Eventually, this additional chiral center could even induce a certain direction of the C=0 groups (e.g. LAP being more stable than LAM, and consequently DAM more stable than DAP). 

One of the first facts observed in regard to uric acid was that on heating it yielded cyanuric acid, (OCNH)3, and ammonia, NH3. As these same products had been obtained by heating urea, OC(NH2)2, it was considered probable that a urea residue was present in uric acid. It was then shown that on oxidation with lead dioxide, one of the ureids, the di-ureid known as allantoin was obtained, together with urea, oxalic acid and carbon dioxide. With other oxidizing agents, such as nitric acid, the products were equal molecules of urea and the two ureids alloxan and parabanic acid. From alloxan there may be obtained, by reduction, two other ureids, viz., barbituric acid and... 

From the facts that uric acid yields the di-ureid allantoin and also equal molecules of alloxan, a mono-ureid, and urea it was concluded that uric acid must contain two urea residues. From the constitution of alloxan and its reduction products, barbituric and dialuric acids, uric acid must likewise contain a three carbon chain linked to a urea residue by the end carbon atoms. Also, as it yields parabanic acid or oxalyl urea, one of the urea residues must be linked to two adjacent carbon atoms in this chain. 

In addition to a bifunctional molecule, a trifunctional molecule has been illustrated to self-assemble to give a homodimer. Specifically, Alajarin and Steed have demonstrated the ability of a tris(o-ureido-benzyl)amine to form a homodimer in the solid state (Fig. 5).13 Urea residues formed a belt of 12 hydrogen bonds along the equator to hold the two components together. 

Structure of Uric Acid.—The formation of allantoine from uric acid is evidence that the latter contains two urea residues, and the formation of alloxan that it contains the arrangement of atoms represented by the symbols,—... 

Kappelmeier [35] has suggested the use of aniline, benzylamine, and phenyl-ethyl-amine as reagents for the identification and analysis of urea in UF resins. He has provided evidence that the methylene-ether groups form a bridge between urea residues in UF resins. The use of benzylamine in particular (which yields dibenzylurea from urea derivatives), has been developed as a method of analysis. In determining the ratio of urea to formaldehyde in UF resins, the benzylamine method has been coupled with a process of formaldehyde estimation which involves depolymerization with phosphoric acid, followed by distillation into alkaline potassium cyanide solution [36]. 

The metabolism of Monuron in the rat consists of oxidative A -demethyla-tions, ring hydroxylation, and, to a limited extent, degradation of the urea residue to yield an aromatic amine. Using four microbial systems, Simmon et tested 20 pesticides, including Monuron, Simazine 120), and PCNB 224) no positive results were reported for these pesticides with or without S-9 in Salmonella or the other systems. 

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