Ureas, reaction with carbonyl chloride

The reaction of substituted ureas with carbonyl chloride provides another useful method of synthesis of chloroformamidines However, oxygen is not as nucleophilic as sulfur and consequently attack on nitrogen often occurs. In the case of 1,3-dialkylureas good yields of... 

However, the reaction of tri- and tetrasubstituted ureas with carbonyl chloride affords high yields of the chloroformamidine hydrochlorides ( ). 

Barbituric acid can be considered as a cyclized malonic acid diamide (malonyl-urea). It is therefore a cyclic diketone that may be classified, in the sense of the compounds discussed in Section 12.6, as a coupling component with a methylene group activated by two carbonyl groups in the a- and a -positions. The reaction with arenediazonium salts was studied by Nesynov and Besprozvannaya (1971). These authors obtained coupling products (in good yield) that they considered to be arylhydrazones. Coupling with 4-(phenylazo)benzenediazonium chloride was studied by Chandra and Thosh (1991). The lH NMR spectra of these compounds are consistent with the arylhydrazone structure 12.68. 

Primary amines react with phosgene (carbonyl chloride) to give isocyanates [38] faster than ureas at temperatures below about 100°C. For example, aniline reacts with phosgene to give phenyl isocyanate below 100°C, but carbani-lide is produced when the reaction mixture is warmed at 140°C unless excess phosgene is used [39]. 

The reactions of 2-aminobenzimidazoles have been reviewed <83S86l>. The compounds form Schiffs bases with carbonyl compounds, with isocyanates and isothiocyanates they give ureas and thioureas, they are subject to 1,3-dipolar addition reactions, and to the formation of carbamates on acylation and aroylation. When aminoimidazoles are acylated there is frequently competition between the annular and exocyclic nitrogen (see above). Add chlorides and anhydrides (soft) acylate the amino group chlorocarbonic acid esters (hard) are specific for the heteroatom <84CHE204>. When heated, the A -acyl products isomerize (Scheme 91). 

In general, chloroformamidine hydrochlorides are formed in the reaction of thiourea and urea derivatives with either carbonyl chloride or... 

The following section highlights some selected recent applications of the use of phosgene equivalents in the preparation of Vilsmeier-type chlorinated derivatives of amides and ureas. Thionyl chloride, carbonyl bromides, phosphorus oxychloride, phosgene, triphosgene, oxalyl chloride, and p-toluenesulfonyl chloride are all efficient oxophilic promoters capable of generating Vilsmeier-type chloro imi-nium ion intermediate 1770 by reaction with formamides, particularly dimethyl-formaraide, and ureas. 

Alkaline solutions of mononitroparaffins undergo many different reactions when stored for long periods, acidified, or heated. Acidification of solutions of mononitro salts is best effected slowly at 0°C or lower with weak acids or buffered acidic mixtures, such as acetic acid—urea, carbon dioxide, or hydroxyl ammonium chloride. If mineral acids are used under mild conditions, eg, dilute HCl at 0°C, decomposition yields a carbonyl compound and nitrous oxide (Nef reaction). 

The solvent process involves treating phthalonitrile with any one of a number of copper salts in the presence of a solvent at 120 to 220°C [10]. Copper(I)chloride is most important. The list of suitable solvents is headed by those with a boiling point above 180°C, such as trichlorobenzene, nitrobenzene, naphthalene, and kerosene. A metallic catalyst such as molybdenum oxide or ammonium molybdate may be added to enhance the yield, to shorten the reaction time, and to reduce the necessary temperature. Other suitable catalysts are carbonyl compounds of molybdenum, titanium, or iron. The process may be accelerated by adding ammonia, urea, or tertiary organic bases such as pyridine or quinoline. As a result of improved temperature maintenance and better reaction control, the solvent method affords yields of 95% and more, even on a commercial scale. There is a certain disadvantage to the fact that the solvent reaction requires considerably more time than dry methods. 

Newman and Lola236 observed that, when 3-chloro-3-phenylphthalide (1) is allowed to react with methanol in the cold, the pseudo ester (2) produced on standing in the presence of the hydrogen chloride reacts rapidly by addition of methanol to the carbonyl group to give the normal methyl ester (3). They found that added urea effectively neutralizes the mineral acid and suppresses the reaction of (2) to give (3). This... 

B. Polymeric Urea [Benzene, diethenyl-, polymer with ethenylbenzene, [[[[(l-methylethyl)amino]carbonyl ]amino]niethyl]deriv.] A 10.0-g. portion of benzylamine polymer beads prepared as in Part A and 125 ml. of tetrahydrofuran (Note 6) are combined in a 300-ml., three-necked, round-bottomed flask equipped with a magnetic stirrer, a dropping funnel, and a condenser fitted with a gas-inlet tube. A nitrogen atmosphere is established in the sj stem, and the slurry is stirred while 1.35 g. (0.0159 mole) of isopropyl isocyanate [Propane, 2-isocyanato-] is added. This causes an exothermic reaction, which subsides after about 20 minutes. The mixture is then stirred at room temperature for 22 hours and at reflux for an additional 4 hours. The beads are collected by filtration, washed with 150-ml. portions of tetrahydrofuran (Note 6) and methanol, and dried under reduced pres.sure over calcium chloride to jdeld 9.09 g. of the isopropyl urea polymer. 

A very useful group of procedures for oxidation of alcohols to ketones have been developed that involve dimethyl sulfoxide (DMSO) and any one of a number of electrophilic molecules, particularly dicyclohexylcarbodiimide, acetic anhydride, trifluoroacetic anhydride, oxalyl chloride, and sulfur trioxide. The initial work involved the DMSO-dicyclohexylcarbodiimide system.The utility of the method has been greatest in the oxidation of molecules that are highly sensitive to more powerful oxidants and therefore cannot tolerate alternative methods. The mechanism of the oxidation involves formation of intermediate A by nucleophilic attack of DMSO on the carbodiimide, followed by reaction of this species with the alcohol. A major part of the driving force for the reaction is derived from the conversion of the carbodiimide to a urea, with formation of an amide carbonyl. ... 

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