Substitution ureas

Mono-substituted and unsymmetrical di-substituted ureas may be prepared by a modification of Wohler s urea synthesis, salts of primary or secondary amines being used instead of the ammonium salt for interaction with potassium cyanate. Thus when an aqueous solution containing both aniline hydrochloride and potassium cyanate is heated, aniline cyanate is first formed, and then C,HjNH,HCl -h KCNO = C,H6NHj,HCNO -h KCl C,HsNH HCNO = C.H NHCONH, by the usual molecular rearrangement is converted into monophenyburea. 

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. 

The introduction of DNOC was followed by the appearance in the 1940s of the substituted phenoxy acids, and in 1951 of the substituted ureas. 

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. ... 

Although most nonionic organic chemicals are subject to low energy bonding mechanisms, sorption of phenyl- and other substituted-urea pesticides such as diuron to sod or sod components has been attributed to a variety of mechanisms, depending on the sorbent. The mechanisms include hydrophobic interactions, cation bridging, van der Waals forces, and charge-transfer complexes. 

Pesticide Solvent. The majority of organic fungicides, insecticides, and herbicides (qv) are soluble in DMSO, including such difficult-to-solvate materials as the substituted ureas and carbamates (see Fungicides, agricultural Insect control technology Pesticides). Dimethyl sulfoxide forms cosolvent systems of enhanced solubiUty properties with many solvents (109). 

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). 

Chemical antiozonants comprise the second general class of commercial antiozonants. Of the many compounds reported to be chemical antiozonants, nearly all contain nitrogen. Compound classes include derivatives of l,2-dihydro-2,2,4-trimethylquinoline, A/-substituted ureas or thioureas, substituted pyrroles, and nickel or zinc dithiocarbamate salts (see also Antioxidants). The most effective antiozonants, however, are derivatives of -phenylenediamine... 

Amines react with CO in the presence of metal carbonyls forming /V-formyl derivatives or substituted ureas (152,153). 

ALkylenearnines, like AEP, react with urea [57-13-6] to form substituted ureas and ammonia (41). 

IV-Alkyl substituted ureas usually eliminate the IV-substituted amine (80JHC235), but IV-arylthioureas may give ring IV-aryl derivatives 66UC447). 

After the addition of the last of the /)-nitroaniline, the stream of phosgene is continued for five minutes and then shut off. The flame under the flask is then turned up and the ethyl acetate distilled. Care must be taken at the end not to overheat the residue. The brown residue (Note 5) is treated with 800 cc. of hot dry carbon tetrachloride, and the insoluble residue (the di-substituted urea) is removed by filtration. 

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... 

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]. 

The mechanism involves the initial formation of a substituted urea followed by ring closure to form the thiohydantoin. The amino acid is dissolved in 60% aqueous pyridine containing the phenylisothiocyanate... 

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 ... 

Mechanism of action can be an important factor determining selectivity. In the extreme case, one group of organisms has a site of action that is not present in another group. Thus, most of the insecticides that are neurotoxic have very little phytotoxicity indeed, some of them (e.g., the OPs dimethoate, disyston, and demeton-5 -methyl) are good systemic insecticides. Most herbicides that act upon photosynthesis (e.g., triaz-ines and substituted ureas) have very low toxicity to animals (Table 2.7). The resistance of certain strains of insects to insecticides is due to their possessing a mutant form of the site of action, which is insensitive to the pesticide. Examples include certain strains of housefly with knockdown resistance (mutant form of Na+ channel that is insensitive to DDT and pyrethroids) and strains of several species of insects that are resistant to OPs because they have mutant forms of acetylcholinesterase. These... 

Several metal complexes have been described with urea, thiourea or dimethyl derivatives [49,50]. We will focus in this section on the coordination chemistry of substituted ureas and thioureas used as neutral Ugands as well as many ureato and thioureato anions complexed to metal centres. 

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... 

---