Alkylureas

The alkylurea 576 and oxamide 577 are formed by oxidative carbonylation of amines under CO pressure using Pd/C as a catalyst[518]. The urea formation proceeds under atmospheric pressure using PdCh and CuCl2[519]. The mono-and double carbonylations of / -aminoethanol (578 and 579) afford the cyclic carbamate (oxazolidinones) 580 and oxamide (morpholinediones) 581 [520,521]. 

In the total synthesis of zearaienone (451), the ester 450 was prepared by the carbonylation of the crowded aryl iodide 448. The alkyl iodide moiety in the alcohol molecule 449 is not attacked[306]. Methyl trifluoromethacrylate (453) was prepared by the carbonylation of 3,3,3-trifluoro-2-bromopropylcne (452), The carbonylation in the presence of alkylurea affords 454. which is converted into the trifluoromethyluracil 455[307],... 

Diaziridinones (167) are obtained from di-t-alkylureas by Af-chlorination and base-promoted elimination of hydrogen chloride from (279) (69JOC2254). The very unstable c/s-fused diaziridinone (280) could be prepared by a similar but milder procedure (76JOC2813). 

Imino ethers and, in particular, lactim ethers [141] such as O-ethylpyrrolidone 384a [142] or O-trimethylsilylcaprolactam 384b, which is formed, in equilibrium with N-trimethylsilylcaprolactam, on treatment of caprolactam with HMDS 2, condense readily with activated methylene compounds such as methyl or ethyl cyanoacetate to the y9-enamino esters 385 a and 385 b [140] whereas O-alkylureas such as 2-methoxyimidazoline 386 [143-146] afford products such as 387. 

Gold(I) complexes of the type [AuCl(PPh3)ra] (n= 1, 2) or [Au(N03)(PPh3)] show an excellent performance towards oxidative addition carbonylation or aromatic amines to form corresponding carbamates, and also towards the carbonilation of aliphatic amines to produce either alkylureas or formamides.2552,2553 Cationic gold(I) compounds of the type [AuL]+ where L = phosphine, phosphite, or arsine are excellent catalysts for the addition of alcohols to alkynes.2554... 

The structures of 16 copper(II) complexes of bidentate amidino-O-alkylureas ([CuL jyXj) have been determined by single crystal methods [59-61,63-66]. The range of ligands and of copper(II) salts studied is summarised in Table 2. Although the N-alkylamidino-O-alkylurea derivatives form part of the systematic study by Suksangpanya et al. [59-61] [Cu(LHm)2]Cl2 [66], [Cu(LHm)2]Br2 [63], [Cu(LHe)2] Cl2 [64] and [Cu(LHe)2]Br2 [65] were prepared in independent studies. 

Table 3 Mean values and ranges (in parentheses) for the hydrogen-bonded contacts in the extended structures of the structurally characterised bis(AT-alkylamidino-0-alkylurea)copper(II) nitrates, tetrafluoroborates, halides and sulfates...

In a recent series of experiments, Suksangpanya et al. [67] have investigated the interactions between pyrimidine bases and [Cu(Lkl)]2+ cations. Amidino-O-alky-lureas contain an A-D-D sequence, similar to that of guanine. The only difference lies in the oxygen acceptor, which is part of an ether linkage in the amidino-0-alkylurea but part of a carbonyl functionality in guanine. Despite this difference, the formation of a triple complementary interaction between amidino-O-alky-lurea and cytosine, which has a D-A-A sequence was thought to be feasible. 

The potential triple A D D D A A interaction between cytosine and bis(amidino-0-methylurea)ethane, when co-ordinated to copper(II), is shown in Scheme 12 (l.h.s.). Alternative complementary interactions between amidino-O-alkylureas and DNA pyrimidine bases include the double D A A-D interaction with thymine shown in Scheme 12 (r.h.s.). 

A method for analysis of A-nitroso-A-alkylureas (288b) has been developed by forming fluorescent derivatives with sodium sulfide, taurine (77) and o-phthalaldehyde (73)... 

An explanation for these observances in the cases of ethanol and PEG may arise from hydrophobic interactions (i.e., methylene groups, methyl) with the unfolded state of the protein at elevated temperatures. This idea is supported by studies of the interaction of several alkylureas (methyl-, ACVdimethyl-, ethyl-, and butylureas) with the thermal unfolding of ribonuclease A, where it was shown... 

Poklar, N., N. Petrovcic, M. Oblak, and G. Vesnaver. 1999. Thermodynamic stability of ribonuclease A in alkylurea solutions and preferential solvation changes accompanying its thermal denaturation a calorimetric and spectroscopic study. Protein Sci 8 832-840. 

The nitrosation of A-alkylureas in dioxane-acetic acid mixtures is governed by the expression v = fc[HN02][urea], at fixed pH, and dependent on rate-determining proton transfer from the protonated iV-alkyl-iV-nitrosourea to acetate anion the order of reactivity, which reflects relative impediment by the alkyl groups, is as for nitrosation in aqueous media (methyl- ethyl- propyl- butyl- > allyl-urea). 

Amines also react with cyanic acid produced in the decomposition of nitrourea to give 70-95% yields of alkylureas [13-18] (Eqs. 12 and 13). This... 

In contrast to isocyanates, isothiocyanates are relatively unreactive toward hydroxyl-containing compounds thus they are not even affected by aqueous media [31]. Their reaction with hydroxyalkyl thioureas has been reported [32]. With free 2-mercaptoethylamine, 1 mole of phenyl isothiocyanate gave the N-substituted product, l-(2-mercaptoethyl)-3-phenyl-2-thiourea, and 2 moles gave the N,S-disubstituted product. Isocyanates, regardless of the relative amounts, reacted with 2-mercaptoethylamine to give the N,S-disubsti-tuted products. Cleavage with silver nitrate affords the l-(2-mercaptoethyl)-3-alkylureas [33]. 

N-nitroso-N-alkylureas N-nitroso-N-alkylcarbamates N-nitroso-N-alkyl amides... 

In an alternative synthesis (Expt 6.96, Method 2), which is also convenient for the synthesis of alkylureas, the amine hydrochloride is heated in aqueous solution with urea. This reaction also probably involves the amine cynate since in aqueous solution urea serves as a source of ammonium cyanate. 

Blake, A.J., Hubberstey, P., Suksangpanya, U., and Wilson, C. Anion recognition by conservation of hydrogen-bonding patterns in salts of copper(II) co-ordinated by tetradentate bis(amidino-0-alkylurea) ligands, Dalton Trans. (2000), 3873-3880. 

Better results are obtained when the alkylation of ureas is performed in toluene in the presence of a phase-transfer catalyst (Scheme 6.28). This method enables the use of primary alkyl bromides as alkylating agents and both N-aryl or N-alkylureas as substrates. 

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