Substituted urea reaction

The substituted urea reaction is shown as the second item of Fig. 1. The reaction of an amine and an isocyanate is quite rapid at room temperature and often does... 

The amine group of 3-arninoben2otrifluoride can be replaced by Cl, Br, I, F, CN, or OH groups by standard dia2oti2ation reactions. Phosgenation gives 3-trifluoromethylphenyhsocyanate [329-01-1/, which can then be converted to the selective herbicide fluometuron [2164-17-2] a substituted urea. Application. 

Industrially, polyurethane flexible foam manufacturers combine a version of the carbamate-forming reaction and the amine—isocyanate reaction to provide both density reduction and elastic modulus increases. The overall scheme involves the reaction of one mole of water with one mole of isocyanate to produce a carbamic acid intermediate. The carbamic acid intermediate spontaneously loses carbon dioxide to yield a primary amine which reacts with a second mole of isocyanate to yield a substituted urea. 

Carboxyhc acids react with aryl isocyanates, at elevated temperatures to yield anhydrides. The anhydrides subsequently evolve carbon dioxide to yield amines at elevated temperatures (70—72). The aromatic amines are further converted into amides by reaction with excess anhydride. Ortho diacids, such as phthahc acid [88-99-3J, react with aryl isocyanates to yield the corresponding A/-aryl phthalimides (73). Reactions with carboxyhc acids are irreversible and commercially used to prepare polyamides and polyimides, two classes of high performance polymers for high temperature appHcations where chemical resistance is important. Base catalysis is recommended to reduce the formation of substituted urea by-products (74). 

An excess of phosgene is used during the initial reaction of amine and phosgene to retard the formation of substituted ureas. Ureas are undesirable because they serve as a source for secondary product formation which adversely affects isocyanate stabiUty and performance. By-products, such as biurets (23) and triurets (24), are formed via the reaction of the labile hydrogens of the urea with excess isocyanate. Isocyanurates (25, R = phenyl, toluyl) may subsequendy be formed from the urea oligomers via ring closure. 

Amide yields of up to 90—95% are reported from lauric acid and urea (1 1 mole ratio) by ramping the reaction temperature from 140 to 190°C over 4 hours. Oleic, stearic, linoleic, and ricinoleic acids gave similar results (19,20). The reaction does not form significant quantities of bisamides, but rehes on the decomposition of a substituted urea amide, releasing CO2 and NH. ... 

First, it should be noted that the /V-methy1o1 group is activated by the carbonyl group. This reactive group is present in almost all /V-methy1o1 systems. Second, the reaction is an equiUbrium reaction so that both forward and reverse reactions can occur. Third, the agent is not simply a dimethylol agent, but is predominandy a mixture of mono- and di-substituted ureas. 

The steric effects in isocyanates are best demonstrated by the formation of flexible foams from TDI. In the 2,4-isomer (4), the initial reaction occurs at the nonhindered isocyanate group in the 4-position. The unsymmetrically substituted ureas formed in the subsequent reaction with water are more soluble in the developing polymer matrix. Low density flexible foams are not readily produced from MDI or PMDI enrichment of PMDI with the 2,4 -isomer of MDI (5) affords a steric environment similar to the one in TDI, which allows the production of low density flexible foams that have good physical properties. The use of high performance polyols based on a copolymer polyol allows production of high resiHency (HR) slabstock foam from either TDI or MDI (2). 

This reaction is reported to proceed at a rapid rate, with over 25% conversion in less than 0.001 s [3]. It can also proceed at very low temperatures, as in the middle of winter. Most primary substituted urea linkages, referred to as urea bonds, are more thermally stable than urethane bonds, by 20-30°C, but not in all cases. Polyamines based on aromatic amines are normally somewhat slower, especially if there are additional electron withdrawing moieties on the aromatic ring, such as chlorine or ester linkages [4]. Use of aliphatic isocyanates, such as methylene bis-4,4 -(cyclohexylisocyanate) (HnMDI), in place of MDI, has been shown to slow the gelation rate to about 60 s, with an amine chain extender present. Sterically hindered secondary amine-terminated polyols, in conjunction with certain aliphatic isocyanates, are reported to have slower gelation times, in some cases as long as 24 h [4]. 

In most cases, the allophanate reaction is an undesirable side reaction that can cause problems, such as high-viscosity urethane prepolymers, lower pot lives of curing hot-melt adhesives, or poor shelf lives of certain urethane adhesives. The allophanate reaction may, however, produce some benefits in urethane structural adhesives, e.g., additional crosslinking, additional modulus, and resistance to creep. The same may be said about the biuret reaction, i.e., the reaction product of a substituted urea linkage with isocyanate. The allophanate and biuret linkages are not usually as thermally stable as urethane linkages [8]. 

Amines, too, possess active hydrogens in the sense required for reaction with an isocyanate group. Thus the products of Reaction 4.10 react further to yield substituted ureas by the process shown in Reaction 4.11. Reaction can proceed still further, since there are still active hydrogens in the urea produced in Reaction 4.11. The substance that results from the reaction between an isocyanate and a urea is called a biuret (see Reaction 4.12). 

Ammonia and primary and secondary amines can be added to isocyanates to give substituted ureas. Isothiocyanates give thioureas. This is an excellent method for the preparation of ureas and thioureas, and these compounds are often used as derivatives for primary and secondary amines. Isocyanic acid (HNCO) also gives the reaction usually its salts (e.g., NaNCO) are used. Wohler s famous synthesis of urea involved the addition of ammonia to a salt of this acid. "... 

Salts of dithiocarbamic acid can be prepared by the addition of primary or secondary amines to carbon disulfide. This reaction is similar to 16-9. Hydrogen sulfide can be eliminated from the product, directly or indirectly, to give isothiocyanates (RNCS). Isothiocyanates can be obtained directly by the reaction of primary amines and CS2 in pyridine in the presence of DCC. ° In the presence of diphenyl phosphite and pyridine, primary amines add to CO2 and to CS2 to give, respectively, symmetrically substituted ureas and thioureas ... 

A fused heterocyclic compound (146) distantly related to the antiinflammatory agent cintazone (Chapter 12), which itself can be viewed as a cyclized derivative of phenylbutazone, retains the activity of the prototype, in the synthesis of 146, reaction of the nitroaniline 139 with phosgene gives intermediate 140, which is then reacted with ammonia to afford the substituted urea (141). Cyclization of the ortho nitrourea function by means of sodium hydroxide leads to the N-oxide (142) this last reaction represents... 

The preparation of optically active analogues of the natural amino acids has proven reasonable using the reaction of tris(trimethylsilyl) phosphite with chiral aldimines prepared from optically active amines.225 The asymmetric induction has been observed to be as high as 80%, a significant competitive process compared to the multistep approaches available.226227 An alternative one-step approach involving asymmetric induction upon addition to an aldimine derived from a chiral N-substituted urea provided a product with less desirable optical purity.228... 

If the ring nitrogen atom forms a secondary amine, its reaction with aryl isocyanate can yield substituted ureas and this transformation is strongly related to a N-acylation. In this respect, a publication by Saczewski and Nasal <1995APH237> should be mentioned here these authors described the transformation of 119 with a number of arylisocyanates to the urea 120 in medium to high yields (49-82%) (Scheme 17). 

Reaction with amines gives substituted ureas (cf. methylurea p. 271) —with hydrazine for example, semicarbazide ... 

Thiourea and its /V-substituted derivatives readily reacted with EMME in hot ethanolic sodium ethoxide to yield 2-thiopyrimidine-5-carboxylates (219) (42JA794 56JA5294), With N-substituted thiourea, as in the case of -substituted urea, the primary amino group was first involved in the reaction. 

Dioxotetrahydropyrimidine-5-carboxylates (1341) were prepared in 50-72% yields, by the cyclization of (V-(aminocarbonyl)aminomethy-lenemalonates (1340) in alcohol by the action of sodium alcoholate, or in 48-97% yields in the reaction of /V-substituted urea and EMME in ethanol in the presence of sodium ethylate at room temperature for several days. Compounds 1341 were also prepared in 41 and 62% yields, respectively, in the reactions of N-methyl- and /V,N -dimethylurea and EMME in the melt at 120°C for 24 hr (52JA4267). 

The versatility of the PCH2/KI catalytic system is further demonstrated by its ability to catalyze the oxidative carbonylation of primary amines to symmetrically substituted ureas (Eq. 51), still under mild conditions (100 °C, 16 atm of CO, 4 atm of air in DME as the solvent) and with unprecedented catalytic efficiencies for this kind of reaction (up to ca. 2500 mol of product per mol of Pd) [274,275]. In some cases, working in the presence of an excess of CO2 (40 atm) had a beneficial effect on the reaction rate and product selectivity. 

The alkylating agent (20 mmol) is added to the (V-substituted urea (20 mmol), NaOH (3.2 g), K2C03 (0.55 g), and TBA-CI (0.28 g, 1 mmol) in toluene (40 ml). The mixture is stirred under reflux until the reaction is complete (ca. 2 h) and then cooled, poured into H20 (150 ml), and extracted with CHCI, (50 ml) and CH2CI2 (50 ml). The organic solutions are washed with H20 (50 ml), dried (Na2S04), and evaporated to yield the disubstituted urea. 

More than 25 different substituted urea herbicides are currently commercially available [30, 173]. The most important are phenylureas and Cycluron, which has the aromatic nucleus replaced by a saturated hydrocarbon moiety. Benzthiazuron and Methabenzthiazuron are more recent selective herbiddes of the class, with the aromatic moiety replaced by a heterocyclic ring system. With the exception of Fenuron, substituted ureas (i.e., Diuron, Fluometuron, Fig. 10, Table 3) exhibit low water solubilities, which decrease with increasing molecular volume of the compound. The majority of the phenylureas have relatively low vapor pressures and are, therefore, not very volatile. These compounds show electron-donor properties and thus they are able to form charge transfer complexes by interaction with suitable electron acceptor molecules. Hydrolysis, acylation, and alkylation reactions are also possible with these compounds. 

Guanidines have been prepared by the reaction between an amine, or an amine salt, and a host of other reagents, such as a thiourea in the presence of lead or mercuric oxide [83, 157, 158], carbodi-imides [140, 174, 175],calcium cyanamide [176, 177], isonitrile dichlorides [178—180], chloroformamidines [181], dialkyl imidocarbonates [182], orthocarbonate esters [183], trichloro-methanesulphenyl chloride [184], and nitro- or nitroso-guanidines [185-188]. Substituted ureas can furnish guanidines, either by treatment with amines and phosphorus oxychloride [189], or by reaction with phenylisocyanate [190] or phosgene [191]. 

In the search for more effective post-emergent herbicides, many laboratories have measured the inhibition of photosystem II in chloroplasts i.e., the Hill reaction. In a continuing investigation of this system, ( ) Corwin Hansch s group at Pomona College, in cooperation with BASF in Germany, analyzed two sets of phenyl substituted ureas 17 1,1-dimethyl-3-phenyl, and 38... 

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