Condensation of amines

Group of plastics generated by the condensation of amines (e.g., urea and melamine with aldehydes). 

Discovered more than a century ago, the Knorr and Paal-Knorr (PK) pyrrole syntheses are similar intermolecular condensations of amines with carbonyl compounds to give pyrroles. 

Amines are derived from ammonia by the replacement of hydrogen atoms with organic groups. Amides result from the condensation of amines with carboxylic acids. Amines and many amides take part in hydrogen bonding. 

Amines can react with various carbonyl compounds and their derivatives in aqueous media to give the corresponding imine derivatives. These reactions have been discussed in related chapters. The synthetically most useful reaction of this type is the formation of imines and imine derivatives from the condensation of amines with aldehydes and ketones. Water is an excellent solvent for such condensation reactions. For example, water was found to be an ideal solvent for a high-yield, fast preparation of easily hydrolyzable 2-pyrrolecarbaldimines.23 In the presence of Cu2+, the reaction afforded the corresponding Cu(II) chelates (Eq. 11.19). 

Condensations of amine hydrohalides with potassium thiocyanate (KSCN) provide both the primary thioureas and symmetrical 7V,7V -disubstituted thioureas. Selectivity in the product was achieved by changing the concentration of KSCN as shown in the diagram (Scheme 50).131... 

The first reported synthesis of hydroxyurea (24) consists of the condensation of hy-droxylamine with potassium cyanate (Scheme 7.14) [87]. Condensation of hydroxy-lamine with ethyl carbamate also gives pure hydroxyurea in good yield after recrystallization (Scheme 7.14) [88]. Nitrogen-15 labeled hydroxyurea provides a useful tool for studying the NO-producing reactions of hydroxyurea and can be prepared by the condensation of N-15 labeled hydroxylamine with either potassium cyanate or trimethylsilyl isocyanate followed by silyl group removal (Scheme 7.14) [89, 90]. Addition of hydroxylamine to alkyl or aryl isocyanates yields alkyl or aryl N-hydroxyureas (Scheme 7.14) [91, 92]. The condensation of amines with aromatic N-hydroxy carbamates also produces N-substituted N-hydroxyureas (Scheme 7.14) [93]. 

While the condensation of amines with nitroso compounds appears to have wide applicability in the benzene series, it seems to lead to complex dye molecules in the naphthalene series. A method has been developed using a somewhat complex reaction between thionylamines and substituted hydroxylamines which does produce azo compounds derived from naphthalenes. This synthesis is of particular interest because it helped to settle the question whether true naphthylazo compounds with hydroxyl groups could exist [36]. 

The most practical laboratory methods involve the condensation of amines with either ureas, isocyanates, or isocyanate derivatives. The use of difunctional reactants yields polymers (Eq. 1). 

CONDENSATION REACTIONS A. Condensation of Amines with Carbonyl Compounds... 

Catalysis in reaction systems with undissolved substrates and products is not restricted to biocatalysis. High yields in sobd-state synthesis, sohd-to-sohd reactions, and solvent-free systems have also been reported for aldol condensation, Baeyer-Villiger oxidation, oxidative coupling of naphthols, and condensation of amines and aldehydes [1, 2]. 

Condensation of amine 277 with dimethylformamide dimethylacetal (DMF/DMA) gave A, A-dimethyl-./V -(5-methyl-l, 2,4-triazolo[l, 5-a]pyrim-idin-7-yl)formamidine (278), whose reaction with hydroxylamine gave the formamidoxime 279 (89EGP264438 90ZC320).The amine 280 and the hydrazine 282 can be transformed into the amidine 281 and amidrazone 283, respectively (90ZC320) (Scheme 54). 

Carbamate-bound guanidines have been prepared by the condensation of amines with thioureas linked to insoluble supports as carbamates [519]. The direct reaction of guanidines with resin-bound carbonates or other alkoxycarbonylating agents requires the use of chloroformates or other reactive carbonic acid derivatives [520,521], Carbamate-bound amidines (Entries 7 and 8, Table 3.28) have been prepared by the reaction of amidines with resin-bound 4-nitrophenyl carbonates (0.9 mol/L amidine in DMF/DIPEA, > 4 h [522-524]). 

Other well-established methods include the condensation of amine hy-... 

The position of the equilibrium between imine and carbonyl may be perturbed by interaction with a metal ion. We saw in Chapter 2 how back-donation of electrons from suitable orbitals of a metal ion may stabilise an imine by occupancy of the jc level. It is possible to form very simple imines which cannot usually be obtained as the free ligands by conducting the condensation of amine and carbonyl compounds in the presence of a metal ion. Reactions which result in the formation of imines are considered in this chapter even in cases where there is no evidence for prior co-ordination of the amine nucleophile to a metal centre. Although low yields of the free ligand may be obtained from the metal-free reaction, the ease of isolation of the metal complex, combined with the higher yields, make the metal-directed procedure the method of choice in many cases. An example is presented in Fig. 5-47. In the absence of a metal ion, only low yields of the diimine are obtained from the reaction of diacetyl with methylamine. When the reaction is conducted in the presence of iron(n) salts, the iron(n) complex of the diimine (5.23) is obtained in good yield. 

Key Mechanism 18-5 Formation of Imines 851 18-16 Condensations with Hydroxylamine and Hydrazines 853 Summary Condensations of Amines with Ketones and Aldehydes 854 18-17 Formation of Acetals 855... 

SUMMARY Condensations of Amines with Ketones and Aldehydes... 

Template-assisted condensations of amines with formaldehyde yield a wide variety of macrocyclic products. Sepul-chrates (7) can be synthesized from the template-assisted condensation of [Co(en)3] + with formaldehyde and ammonia under basic conditions. Primary aldehydes other than formaldehyde have also been used. Caged metal ion complexes in which the metal ion is used as a template are normally... 

Most primary and secondary amines replace halogen more rapidly than ammonia6. Condensation of amines with 2,4-dinitrophenyl halides was used to prepare derivatives for... 

Condensation of Amines with Saturated Electrophilic Carbon... 

Condensation of amines on fluorobenzenes is nothing less than curious. Indeed, for the first time we met a strong difference in the nature of formed products between NaNH2 in HMPA-THF and a complex base (here NaNH2-f-AmONa) in THF. Our observations are illustrated in Scheme 23. 

It is noteworthy that direct substitutions need the presence of NaNH2. In other words, there is no condensation of amine on fluorobenzenes in HMPA—THF without sodamide. 

The presence of impurities can complicate purifications and decrease isolated yields. Impurities that are difficult to remove are particularly costly for the final step in making a drug substance. For example, the condensation of amine 1 and... 

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