First practical synthesis of formamidine ureas and derivatives

Isonitriles and ureas undergo a condensation reaction in the presence of acid chlorides to give formamidine ureas, for which no general synthetic routes currently exist. A mechanism is proposed in which the key intermediate is an electrophilic adduct of isonitrile and acid chloride. The process is tolerant of moderate variability in the nature of the components, and access to formamidine ureas of varying substitution patterns is further enhanced by a facile exchange reaction with amines. [reaction: see text]     

Syntheses, addition-eliminations, and addition-displacements of 5-(bromomethylene)hydantoins

5-(Bromomethylene)hydantoins, prepared from bromopyruvic acid and ureas in the presence of BF₃, react with various nitrogen, phosphorus, sulfur, and carbon nucleophiles by addition-elimination to give the corresponding 5-(substituted-methylene)hydantoins. The 5-(bromomethylene)hydantoins also undergo acid-catalyzed reactions with nucleophiles by addition-displacement and addition-elimination processes.     

W(CO)6-catalyzed oxidative carbonylation of primary amines to N,N'-disubstituted ureas in single or biphasic solvent systems. Optimization and functional group compatibility studies

Primary amines undergo carbonylation to N,N'-disubstituted ureas using W(CO)6 as the catalyst, I2 as the oxidant, and CO as the carbonyl source. Preparation of various N,N'-disubstituted ureas from aliphatic primary amines, RNH2 (R = n-Pr, n-Bu, i-Pr, sec-Bu, or t-Bu), was achieved in good to excellent yields. Studies of functional group compatibility using a series of substituted benzylamines demonstrated broad tolerance of functionality during the carbonylation reaction. Preparation of various N,N'-disubstituted ureas from substituted benzylamines, R-C6H4CH2NH2 (R = H, p-OCH3, p-CO2H, p-CO2Et, p-CH2OH, p-SCH3, p-vinyl, p-Cl, p-Br, m-I, p-NH2, p-NO2, or p-CN), was achieved in good yields. For many substituted benzylamines, yields of ureas were higher when a two-phase CH2Cl2/H2O solvent system was used.     

Recyclization of 4,5-diphenyloxazolin-2-one and -2-thione under the influence of amines

4,5-Diphenyl-4-oxazolin-2-one and -2-thione undergo recyclization to 1-substituted 4,5-diphenyl-4-imidazolin-2-ones and -2-thiones, respectively, under the influence of primary amines. The action of hydrazine hydrate on the oxazolone leads to 5,6-diphenyl-1,2,3,4-tetrahydro-1,2,4-triazin-3-one. The corresponding ureas were isolated from the reaction mixtures in a number of cases.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1028–1030, August, 1981.     

Radical hydroxyalkylation of C-H bond adjacent to nitrogen of tertiary amides, ureas, and amines

Tertiary amides, ureas, and amines undergo direct intermolecular addition to aldehydes under the Et3B/air conditions, thereby providing a unique and simple means for the radical sp3 C-H transformation of nitrogen-containing molecules.     

Conversion of 2-aminomethylbenzothiazoles into imidazo[5, 1-b]benzothiazoles

A number of substituted 2-aminomethylbenzothiazoles ate synthesized. The corresponding ureas or thioureas are also obtained by reaction with arylisocyanates or arylisothiocyanates. Heating the substituted ureas or thioureas at temperatures above their melting points cyclizes them to 9-substituted 2-hydroxy- or 2-mercaptoimidazo[5, 1-b]benzothiazoles, which are derivatives of a new heterocyclic system.     

Condensation of 5-Acetyl-3,4-dihydropyrimidin-2(1H)-ones with Hydrazine

Russian Journal of Organic Chemistry - 3,4-Dihydropyrimidines obtained by the Biginelli reaction react with hydrazine to give a mixture of N-[(3,5-dimethyl-1H-pyrazol-4-yl)(R)methyl]ureas and...     

Additionsreaktionen von 3-Dimethylamino-2,2-dimethyl-2H-azirin an Phenylisocyanat und Diphenylketen

Addition Reaction of 3-Dimethylamino-2,2-dimethyl-2H-azirine with Phenylisocyanate and Diphenylketene 3-Dimethylamino-2,2-dimethyl-2H-azirine ( 1a ) reacts with carbon disulfide and isothiocyanates with splitting of the azirine N(1), C(3)-double bond to give dipolar, fivemembered heterocyclic 1:1 adducts. In some cases, these products can undergo secondary reactions to yield 1:2 and 1:3 adducts. In this paper it is shown that the reaction of 1a with phenylisocyanate also takes place by cleavage of the N(1), C(3)-bond, whereas with diphenylketene N(1), C(2)-splitting is observed. The reaction of 1a and phenylisocyanate in hexane at room temperature yields the 1:3 adduct 2 in addition to the trimeric isocyanate 3 (Scheme 1). A mechanism for the formation of 2 is given in Scheme 5. Hydrolysis experiments with the 1:3 adduct 2 , yielding the hydantoins 4–6 and the ureas 7 and 8 (Schemes 3 and 5), show that the formation of this adduct via the intermediates d , e and f is a reversible reaction. The aminoazirines 1a and 1b undergo an addition reaction with diphenylketene to give the 3-oxazolines 14 (Scheme 8), the structure of which has been established by spectral data and oxidative degradation of 14a to the 3-oxazolin-2-one 15 (R¹ ? R² ? CH₃, Scheme 9).     

Funktionell substituierte zinnorganische Verbindungen. III. (2-Aminoethyl)-triorganostannane

Functionally Substituted Organotin Compounds. III. (2-Aminoethyl)-triorganostannanes The preparation of (2-aminoethyl)-triorganostannanes 1 from 2-chloroethylamin and triorganotin halides is reported. Like primary amines the compounds 1 react with aldehydes, ketones, acyl chlorides or acetic anhydride, isocyanates, isothiocyanates, and hydrogen halides yielding the corresponding triorganostannylethyl substituted azomethines 2 , amides 3 , and 5 , ureas and thioureas 6 , and ammonium halides 7 . Compounds 7 undergo thermal induced fragmentation reaction studied by DTA/TG analysis.     

Dibutyltin oxide catalyzed aminolysis of oxalate to carbamate,oxamate and derivatives of imidazolidine trione

Catalytic aminolysis of oxalates by simple and substituted ureas has been shown to give carbamates, oxamates and derivatives of imidazolidine trione. Various substituted ureas and oxalates were screened to verify the applicability of the protocol. The role of dibutyltin oxide as catalyst, effect of solvent and reaction conditions on product distribution pattern has been discussed. Copyright © 2010 John Wiley & Sons, Ltd.     

Alpha-pyridylation of chiral amines via urea coupling, lithiation and rearrangement

2-, 3- and 4-Bromopyridine, along with other brominated electron-deficient arenes, undergo palladium-catalyzed coupling with ureas of structure RNMeCONHMe. Where R is a chiral, alpha-substituted benzyl group, treatment with LDA leads to a benzylic organolithium which undergoes rearrangement with stereospecific and regiospecific transfer of the pyridyl group, generating a quaternary stereogenic center with high enantioselectivity. Alcoholysis of the urea under neutral conditions reveals the pyridyl amine.     

Pd(OAc)2-catalyzed carbonylation of amines

A phosphine-free catalytic system [Pd(OAc)2-Cu(OAc)2-air] induced a substrate-specific carbonylation of amines in boiling toluene under CO gas (1 atm). Symmetrical N,N'-dialkylureas were obtained by the carbonylation of primary amines. N,N,N'-Trialkylureas were selectively formed by addition of a secondary amine to the above reaction vessel. Secondary amines did not give tetraalkylureas. However, dialkylamines with a phenyl group on their alkyl chains, such as N-monoalkylated benzylic amine or phenethylamine derivatives, underwent a direct aromatic carbonylation to afford five- or six-membered benzolactams. In the carbonylation, the chelation effect or steric repulsion between Pd(II) and the meta-substituent in the ortho-palladation and the ring sizes of cyclopalladation products that were formed prior to carbonylation were found to generate good site selectivity and increase the reaction rate. In contrast, carbonylation of omega-arylalkylamines with a hydroxyl group gave neither ureas nor benzolactams but instead produced 1,3-oxazolidinones smoothly. Hydrochlorides of amines also underwent carbonylation to afford the corresponding amides under the conditions used. This procedure made it possible to prepare ureas of amino acid esters and N-alkylcarbamates in practical yields.     

A novel convenient synthesis of 5-acyl-1,2-dihydropyrimidin-2-ones via 4-trichloromethyl-1,2,3,4-tetrahydropyrimidin-2-ones

A novel four-step methodology for the synthesis of 5-acyl-1,2-dihydropyrimidin-2-ones has been developed. The reaction of readily available N-[(1-acetoxy-2,2,2-trichloro)ethyl]ureas with Na-enolates of 1,3-diketones or β-oxoesters followed by heterocyclization-dehydration of the oxoalkylureas formed gave 5-acyl-4-trichloromethyl-1,2,3,4-tetrahydropyrimidin-2-ones. The latter, in the presence of NaH, eliminate CHCl₃ to give the target compounds.     

New approach to 5-arylsulfonyl-substituted 1,2-dihydropyrimidin-2-ones via base-induced chloroform elimination from 4-trichloromethyl-1,2,3,4-tetrahydropyrimidin-2-ones

A four-step method for the synthesis of 5-arylsulfonyl-substituted 1,2-dihydropyrimidin-2-ones has been developed. The reaction of readily available N-[(1-acetoxy-2,2,2-trichloro)ethyl]ureas with sodium enolates of α-arylsulfonylketones followed by heterocyclization-dehydration of the oxoalkylureas formed gave 5-arylsulfonyl-4-trichloromethyl-1,2,3,4-tetrahydropyrimidin-2-ones. The latter, in the presence of strong bases, eliminate CHCl₃ to give the target compounds.     

Selective catalytic oxidative carbonylation of amino alcohols to ureas

[reaction: see text] Amino alcohols undergo W(CO)(6)-catalyzed oxidative carbonylation to the corresponding hydroxyalkylureas without protection of the hydroxyl group. Selected examples of 1,2-, 1,3-, 1,4-, and 1,5-amino alcohols were converted to the ureas in good to excellent yields, with only small amounts of the cyclic carbamates being formed. In contrast, the phosgene derivatives CDI and DMDTC undergo stoichiometric reactions with the amino alcohol substrates to afford ureas and cyclic carbamates with variable selectivity.     

Synthesis of ureas from titanium imido complexes using CO2 as a C-1 reagent at ambient temperature and pressure

The coordinatively unsaturated 12-electron complex dichloro t-butylimido bispyridine titanium(IV) (2a) has been shown to react with CO(2) to give N,N-bis-t-butyl urea. Two analogous sterically hindered coordinatively saturated 14-electron complexes dichloro t-butylimido trispyridine titanium(IV) (10a) and dichloro 2,6-(i-Pr)(2)phenylimido trispyridine titanium(IV) (10b) also gave their corresponding symmetrical ureas upon treatment with CO(2). Further experiments support the intermediary of metallocycles formed from heterocumulene metathesis reactions. The unsymmetrical urea N-benzyl, N-t-butyl urea (11) was produced from treatment of 2,6-(i-Pr)(2)phenylimido trispyridine titanium(IV) (10b) with CO(2) and interception with BnNH(2). Equimolar quantities of N,N-bistrimethylsilybenzylamine or N,N-bistrimethylsilyphenethylamine were shown to promote the reaction between t-butylimido bispyridine titanium(IV) (2a) and CO(2) to give near quantitative yields of symmetrical urea. Other symmetrical ureas could be produced from TiCl(4), amine and CO(2) in moderate to quantitative yields depending on the stoichiometry of amine present.     

Synthesis of 2-amino-4H-3,1-benzoxazines and 2-amino-4H-3,1-benzothiazines by the rearrangement of <Emphasis Type="Italic">o</Emphasis>-cyclopropylphenylureas and <Emphasis Type="Italic">o</Emphasis>-cyclopropylphenylthioureas

Syntheses are reported for 2-cyclopropylphenylureas and 2-cyclopropylphenylthioureas and the behavior of these compounds was studied under conditions for the acid-catalyzed opening of the cyclopropyl ring. Upon the action of concentrated sulfuric acid or trifluoroacetic acid, these ureas and thioureas can undergo rearrangement to the corresponding 3,1-benzoxazines and 3,1-benzothiazines. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 115–126, January, 2008.     

Non-nanogold catalysis of carbon monoxide oxidative amination

Bulk metallic gold particles ( approximately 1000 nm) catalyze the reaction of CO, O2, and primary amines (R-NH2) to give ureas (RNH)2C=O. Isocyanates (R-N=C=O) are identified as intermediates in the reactions and are shown to react with primary and secondary amines to give ureas under the conditions of the gold-catalyzed reactions. Although many recent studies indicate that nanosized particles of gold are required for the catalytic oxidation of CO, the results presented in this paper show that bulk gold is capable of catalyzing the oxidative amination of CO under mild conditions (45 degrees C, 1 atm CO and O2).     

Reactions of nitroxides with sulfur‐containing compounds,part IV: Synthesis of novel nitroxide (thio)ureas1

The reactions of 4‐isothiocyanato‐2,2,6,6‐tetramethylpiperidine‐1‐oxyl 2 and 4‐isocyanato‐2,2,6,6‐tetramethylpiperidine‐1‐oxyl 3 with selected amines and lower alcohols give the corresponding novel thioureas 4 , ureas 5 , thiocarbamates 6 , and carbamates 7 , all bearing the nitroxyl moiety. The characteristic features of EI mass spectra of (thio)ureas 4 and 5 are described. Some of the synthesized thioureas 4 , ureas 5 , thiocarbamates 6 , and carbamates 7 are moderately or weakly active against pathogenic fungi. © 2006 Wiley Periodicals, Inc. Heteroatom Chem 17:393–401, 2006; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20228     

Selective and environmentally friendly methodologies based on the use of electrochemistry for fine chemical preparation: an efficient synthesis of N,N'-disubstituted ureas

A novel efficient synthesis of N,N'-disubstituted ureas has been developed. Aromatic and aliphatic primary amines undergo oxidative carbonylation under atmospheric pressure of carbon monoxide using Pd(II) catalyst in combination with its anodic recycling at a graphite electrode.