Aliphatic urea derivatives

Of the aliphatic derivatives of urea, one compound, dichloral urea (DCU, 1), 

Prepared from chloral and urea by condensation catalysed with HCl, it is a crystalline compound insoluble in water and stable to acids. In alkaline medium it is decomposed into dichloroacetic acid and urea. In the soil it yields trichloroacetic acid by oxidative decomposition. According to Melnikov (1971a) these reactions 

It irritates the mucous membranes and is hazardous to fish, but is otherwise nontoxic. Its acute oral lDj for rats is 6800 mg/kg. 

DCU is a soil herbicide used at rates of 2-50 kg active ingredient/ha for preemergence treatment in sugar beet, cotton, oil flax, potato, carrots and medicinal herb cultures. In Hungary it is used in combination with Pyramin for weed control in sugar beet (Ubrizsy and Gimesi, 1969). 

It is nonpersistent, even when used at high rates, being broken down in the soil in one growing season. 

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The first compound with significant herbicidal action discovered among aliphatic urea derivatives, N-butyl-N, N -dimethylurea (Searle, 1954) was never put on the market. Others, for example, halo and polyhaloallyl-N,N-dimethyl ureas, also have herbicidal properties, while symmetric tetraalkyl-ureas are inactive. 

Of the aliphatic urea derivatives a single compound, dichloral urea (DCU), has attained some practical importance (King, 1950), combined with Pyramin it is used in Hungary for weed control in sugar beet. 

R NHa + C.HjNCO = RNH CO NHC,Hj Traces of water will contaminate the product with diphenylurea (p. 336) if the solution is boiled hence the need for anhydrous conditions. i-Naphthylisocyanate reacts more slowly with water, and the i-naphthyl-urea derivative can often be obtained using a cold aqueous solution of an aliphatic amine it is particularly necessary in such cases to purify the product by recrystallisation from, or extraction with, boiling petroleum, leaving behind any insoluble di i-naphthylurea. Note that the amine must also be free from alcohols (p. 335) and phenols (p. 337). 

The last example focuses not on the functionalization of heterocycles by a transition metal mediated carbon-heteroatom bond forming reaction, but the palladium catalyzed conversion of primary amines, including amino-heterocycles, into urea derivatives. A representative example, shown in 8.38., includes the reaction of an amino-carbazole derivative with morpholine, carbon monoxide and oxygen in the presence of catalytic amounts of palladium(II) iodide. The formation of the urea moiety proceeds with great selectivity and in high yield.49 The reaction works equally well for primary aliphatic and aromatic amines. 

AT-Substituted amidines 74 are transformed via the carbodiimide intermediate 75 into urea derivatives 76 as shown in Scheme 34 [141]. This reaction has been performed with a variety of aliphatic and aromatic substituents and in addition to (diacetoxyiodo)benzene 3 other hypervalent iodine compounds can also be used for this rearrangement. Phenyl substituted amidines 74 (R = Ph) can lead to cyclized products of type 77. 

Using this protocol, primary aliphatic amines, secondary aliphatic amines, and diamines could be converted into the corresponding urea derivatives in moderate yields. Additionally, catalytic efficiency of cations derived from various bases decreases in the order of > diamines > primary amines > secondary amines > aniline, probably being due to the steric effect and basicity. The catalyst could also be recovered after a simple separation procedure, and reused over five times with retention of high activity. This process presented here could show much potential application in industry due to its simplicity and ease of catalyst recycling. 

Most of the urea derivatives are compounds with herbicidal activity, although some of the aliphatic guanidine derivatives have a fungicidal action and some of the aromatic thioureas a rodenticidal action. 

These are urea derivatives having an arylsulfonyl moiety in the 1 position and an aliphatic fimction at the 3-position. 

Aliphatic nitrile oxides can also be prepared by the dehydration of primary nitro compounds with phenylisocyanate in the presence of a catalytic amount of a tertiary base such as triethylamine. Phenylcarbamate generated in situ on reaction with phenylisocyanate is subsequently converted into urea derivative (Scheme 5.37). 

As for other metals, a catalytic system has been reported in which nitrobenzene was used as an oxidant in an oxidative carbonylation reaction of aliphatic amines [195]. Several aliphatic amines were tested, with piperidine and morpholine being the best. When nitrobenzene was used as an oxidant in the carbonylation of piperidine, the mixed urea PhNHC(0)NHC5Hio was reported among the products in an equation, together with the symmetrical urea deriving from the aliphatic amine, but no detail on the yields of the several products or the precise experimental conditions were reported. 

Chiral Lewis-basic catalysts, in particular phosphoratnides (1 and 2),2-13c. 16.46,47 pyridine iV,iV-bisoxides (3 and and pyridine iV-monoxides (5, 6 and 7,8),3 exhibit very high enantioselectivities for the allylation of aromatic, heteroaromatic, and cinnamyl-type aldehydes with allyl, ( )- and (Z)-crotyl, and prenyl trichlorosilanes. Chiral formamides, pyridine-oxazolines, urea derivatives, and sulfoxides are generally less enantioselective and effective only in stoichiometric quantities. The reaction is much less efficient with aliphatic aldehydes, which require stoichiometric conditions (vide infra). However, a, -unsaturated aldehydes do react readily and give 1,2-addition products. 

Aliphatic amine derivatives such as amides, carbamates and sulfonamides also participate in Pd - catalyzed intramolecular C-N bond formation. The relative reactivity of these amino nucleophiles toward cyclization has been evaluated in the PdCL-catalyzed cyclization of iV-protected 4-pentenylamines and 5-hexenylamines, and it was found to be urea > carbamate > tosylamide > benzamide. The PdCl2(CH3CN)2-catalyzed dehydrative cyclization of alkenyl urethanes bearing an allylic hydroxyl group has been elegantly applied to the synthesis of chiral piperidine alkaloids. The cyclization reaction occurs with complete stereocontrol in good yields in the presence of 15-20 mol % of catalyst without any reoxidant (eq 16). 

Use of the valine derived (4S )-3-acetyl-4-isopropyl-1,3-oxazolidine (8)92, the C2-symmetric reagents (2.5,55)-l-acetyl-2,5-bissubstituted pyrrolidine 994, or the doubly deprotonated acetyl urea /V-acetyl- V..V -bis[(.S)-l-phcnylethyl]urea (10), also does not lead to sufficient induced stereoselectivity combined with acceptable chemical yield. When the acetyl urea enolate is reacted with aliphatic and aromatic aldehydes, the diastereomeric adducts (ratios ranging from 1 1 to 3 1) may be separated by column chromatography to give ultimately both enantiomers of the 3-hydroxy acids in 99% ee110. 

Primary and secondary nitroalkanes, dinitromethane, and terminal em-dinitroaliphatic compounds like 1,1-dinitroethane, all contain acidic protons and have been used to generate Mannich products. Formaldehyde is commonly used in these reactions although the use of other aliphatic aldehydes has been reported. The nitroalkane component is frequently generated in situ from its methylol derivative, a reaction which also generates formaldehyde. Ammonia, " aliphatic amines, " hydrazine, and even urea have been used as the amine component of Mannich reactions. 

The asymmetric Mannich addition of carbon nucleophiles to imines catalyzed by the cyclohexane-diamine catalysts has developed significantly in the past decade. List and co-workers reported the asymmetric acyl-cyanantion of imines catalyzed by a cyclohexane-diamine catalyst [103], Using a derivative of Jacobsen s chiral urea catalyst, the authors optimized reaction conditions and obtained chiral iV-acyl-aminonitriles in high yield and enantioselectivities (Scheme 51). The scope of the reaction was explored with both aliphatic and aromatic imines, providing good to high selectivities for a variety of substrates. 

Carbon disulphide reacts additively with primary and secondary aliphatic amines to form alkylammonium salts of alkyldithiocarbamic acids. The products obtained with dimethylamine, diethylamine and piperidine, also certain derivatives of these products, are manufactured on a large scale for use as accelerators in the vulcanisation of rubber. With aromatic amines the disulphide reacts with elimination of hydrogen sulphide and formation of substituted thio-ureas, e.g. thiocarbanilide. 

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