Urea derivative

1 Urea derivatives This group is easy to recognize by their formulae  

Urea is substituted with one aryl group in one nitrogen and two methyl groups or a methoxy and a methyl group on the other nitrogen. 

Linuron (left structure) was first marketed in the 1960s and has been one of the more popular herbicides in the culture of potatoes and vegetables  

The plants take it up by roots and leaves, and it has a high persistence in humus-rich soil in cool climates, with a half-life of 2 to 5 months. Microorganisms in soil degrade isoproturon, which can be used selectively in various cereal crops, and half-lives of 6 to 28 days have been reported under field conditions, depending on the microbial activity. The aliphatic substitution in the aryl ring is sensitive to microbial oxidative attack. 

Phosgene can react with A/,At -disubstituted ureas at either the oxygen or the nitrogen atom. When attack occurs at the nitrogen atom, ailophanoyl chlorides are formed [2087a]  

The reaction of 1-(arylsulfonyI)-3-aIkylureas with COClj takes place according to the following stoicheiometry [2087a]  

Alkylenebis(3-arylsulfonyl ureas) react readily with phosgene in a similar way to produce the corresponding sulfonyl isocyanate and diisocyanate [2087a]  

In a related reaction, a bis(sulfonyl isocyanate) has been prepared by treating phosgene 

Reaction at the oxygen atom proceeds [585,2087a] to form Vilsmeier-type (chioroformamidinium) saits (see also Section 10.2.2.3)  

Graduate School of Pharmaceutical Sciences, Chiha University, 1-33 Yayoi, Inage, Chiha 263-8522, Japan 

Superbases for Organic Synthesis Guanidines, Amidines, Phosphazenes and Related Organocatalysts Edited by Tsutomu Ishikawa 2009 John Wiley Sons, Ltd. ISBN 978-0-470-51800-7 

Lewis acid like activation recognition and activation 

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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). 

M.p. B.p. Picrate M.p. Acetyl deiiv. M.p. Benzoyl deriv. H.p. Benzene sulph. Onyl deriv. M.p. Toluene p-sulph> onyl deny. M.p. Phenyl urea deriv, M.p. 

Urea derivadves are of general interest in medicinal chemistry. They may be obtained cither from urea itself (barbiturates, sec p. 306) or from amines and isocyanates. The latter are usually prepared from amines and phosgene under evolution of hydrogen chloride. Alkyl isocyanates are highly reactive in nucleophilic addidon reactions. Even amides, e.g. sulfonamides, are nucleophilic enough to produce urea derivatives. 

Exchange reactions known in urea derivatives are reported for the 2-thiazolylurea series (260) (Scheme 156) (488, 489). 

Miscellaneous Resins. Much less important than the melamine—formaldehyde and urea—formaldehyde resins are the methylo1 carbamates. They are urea derivatives since they are made from urea and an alcohol (R can vary from methyl to a monoalkyl ether of ethylene glycol). 

Cyanuric acid can also be prepared by pyrolysis of urea derivatives. Biuret and triuret give less aminotria ines due to reduced ammonia evolution. Urea cyanurate also provides a higher assay product. 

Oxazoles are also obtained by the reaction of a-halogenoketones (78) with primary amides (the Bliimlein-Lewy synthesis), and this method is particularly appropriate for oxazoles containing one or more aryl groups as in (79). Formamide may also be used in this process, resulting in a free 2-position in the oxazole, and when a urea derivative (80) is used, 2-aminooxazoles (81) are formed (80ZOR2185, 78IJC(B)1030, 78JIC264). Numerous applications of these procedures are described in Chapter 4.18. 

Rearrangement of 0-acyi hydroxarrac acxl derivatives with base or heat to amines or urea derivatives (via isocyanates) or rearrangement of carboxylic acids via their hydroxamic acxis to amines... 

Beckmann rearrangement of amidoximes to urea derivatives in the presence ol acids (benaene suMonyl chloride). 

Miscellaneous compounds such as biopesticides (for example. Bacillus thuringiensis and pherhormones), heterocycles (for example, atrazine), pyrethroids (for example, cypermethrin), and urea derivatives (for example, diuron). 

Among the reactions appended to this preparation, the foi-mation of phenylcaibiniide from phenyl mustard oil is desciibetl. It should be noted that phenyl carbimide, like the thiocarbiniide, unites with ammonia, amines, and more especially with alcohols and phenols. The bases yield urea derivatives the alcohols and phenols foim urethanes. 

The reaction of morpholine enamine of cyclohexanone with 1 mole of phenyl isocyanate has been reported (30,31) to give the monoadduet (49), consisting largely of the trisubstituted isomer, and with 2 moles of phenyl isocyanate, the bis adduct (50). That the bis adduct is a dicarboxyanilide rather than a urea derivative (32) such as 51 was shown by its mild hydrolysis to the ketone (52). Reaction of the morpholine enamine of 2-methylcyclo-... 

An early attempt to synthesize rutaecarpine (111) from the urea derivative 110 by a method analogous to that of Clemo and Swan was unsuccessful. ... 

In a somewhat similar vein, alkylation of the urea derivative 109 with methyl iodide affords the S-methyl ether 110. Condensation of that with taurine (111), leads to the guanidine 112, again by an addition elimination process. The product is the anthelmintic agent netobimin (112) [271. 

Preparation of w-Phenyl-tert-Butylamine 24 grams of the urea derivative obtained as indicated above, were well mixed with 96 grams of calcium hydroxide in a flask immersed in an air bath and provided with a dropping funnel the stem of which reached the bottom of the flask. The mixture was heated to 240°-260°C (inside temperature) for 7 hours during which time 86 cc of water was slowly added. The vapors were collected in a receiver cooled with ice. After extraction with ether and distillation, the product was obtained as a colorless liquid boiling from 80°-84 C at 9 mm according to U.S. Patent 2,590,079. 

The synthesis of 2-substituted pyrimidines from 1,3-dicarbonyl compounds and urea derivatives was first described by Evans2 and was later improved by Hunt, McOmie, and Sayer3 for the preparation of 2-mercapto-4,6-dimethylpyrimidine. Burness4 employed 3-ketobutyraldehyde acetal in this procedure to give 2-mercapto-4-methylpyrimidine. 2-Mercaptopyrimidine has been prepared from 1,1,3,3-tetraethoxypropane and thiourea by variations of this basic method 3 6 6 as well as by the reaction of 2-chloropyrimidine with thiourea 1 or sodium hydrosulfide.8... 

This reaction is often used to prepare urea derivatives, an important example being the preparation of barbituric acid ... 

Carbon dioxide reacts with amines (ArNH2) and iodoethane, under electrolysis conditions, to give the corresponding carbamate, (ArNHC02Et). Urea derivatives were obtained from amines, CO2, and an antimony catalyst. ... 

Urea derivative with primary amine groups... 

Usually blue-grey colored chromatogram zones are produced on a colorless [19, 24, 25] to pale grey background [26] cyclochlorotin and simatoxin yield brilliant yellow zones [14] and urea derivatives yellow, green or blue colors [21]. 

For example, ergot alkaloids produce without exception blue chromatogram zones, while clavine alkaloids primarily produce green colors [4], Urea derivatives and primary aromatic amines yield yellow chromatogram zones [28,33,34,36,37] and PR toxin and PR imine emit intense blue fluorescence on excitation with long-wavelength UV light (X = 365 nm) [44],... 

Pesticides and pesticide metabolites e. g. aniline and urea derivatives [4]... 

Amines, amides e.g. hexamine, urea derivatives, melamine resins [1, 2] peptides [3-6] Triazines [7] Vitamin Bj, B2, Bj NH2... 

The asymmetric Strecker-type reaction developed by the Jacobsen group is suitable for both aUphatic and aromatic imines, giving high enantiomeric excesses for a wide range of substrates. In this reaction the urea derivative also acts as the catalyst (Scheme 36). 

Scheme 36. The urea derivative gave similar results to the thiourea compound. Acyclic imines (mainly E isomers) and Z cyclic imines could also be used for this process (Scheme 40,91% ee) [148,152,154].

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