Benzoyl Isocyanate Research Articles

Synthesis of unsymmetrical trisubstituted 1,3,5-triazines compounds

A novel approach has been reported for the synthesis of 1,3,5-triazine with three distinct substituents. The synthesis of the pivotal intermediate 2-chloro-4-R1-6-R2-1,3,5-triazine plays a critical role in achieving 1,3,5-triazine with three different substituents. This article presents two innovative one-pot processes for synthesizing various substituted 2-chloro-4-R1-6-R2-1,3,5-triazines. In the first method, substituted benzoyl isocyanates were initially synthesized by reacting different amides with oxalyl chloride. Subsequently, 21 target products of 2-chloro-4-R1-6-R2-1,3,5-triazines compounds were obtained through the cyclization of substituted benzoyl isocyanates with benzamidine hydrochloride at relatively low temperatures and a one-pot chlorination reaction. The second method involved the synthesis of the same 21 compounds of 2-chloro-4-R1-6-R2-1,3,5-triazines by reacting benzamide with oxalyl chloride followed by cyclization with different amidine hydrochloride and then a one-pot chlorination reaction. Finally, a total of 35 different unsymmetrical trisubstituted 1,3,5-triazine compounds were successfully synthesized using various reactions.

Facile Synthesis, Structural Activity Relationship, Molecular Modeling and In Vitro Biological Evaluation of New Urea Derivatives with Incorporated Isoxazole and Thiazole Moieties as Anticancer Agents

AbstractA new series of isoxazolyl and thiazolyl urea derivatives was synthesized, fully characterized and evaluated in vitro as anticancer agents. The chemistry involves a facile protocol for the preparation of urea derivatives 12–22 through the reaction of isocyanates (p‐tolylsulfonyl isocyanate, p‐tolyl isocyanate, benzoyl isocyanate and ethylisocyanate) 8–11 with the corresponding aminoisoxazoles and aminothiazoles 2, 3, 6 and 7. The cytotoxicity of the synthesized compounds 12–22 were evaluated using human lung adenocarcinoma cell line (A549), cervical cancer cell line (HeLa), and breast cancer cell line (MCF7). All novel compounds (except compounds 12, 17, and 18) were potential cytotoxic against lung cancer as it displayed IC50s less than the reference drug (5‐Fluro uracil (5FU)). All tested compounds (except 15 and 19) showed strong inhibition of breast cancer cell line even much better than the 5FU. The tested compounds were less cytotoxic against cervical cancer except compounds 16, 19, 20, and 21. The molecular docking studies of the synthesized compounds against the three different proteins Janus kinase 2 (JAK2), cyclin dependent kinase‐2 (CDK2), and B‐cell lymphoma‐2 (BCL2) that are major proteins involved in pathogenesis of cancer were discussed. The molecular‐docking analyses revealed that compounds 13, 14 and 20 were the best docked ligand compared to reference docked ligands against the tested targeted proteins. In conclusion, the urea derivatives 13 and 14 were the most promising compounds with lowest IC50s against the tested cancer cell lines, and they displayed the lowest binding energies, critical hydrogen bonds and hydrophobic interactions with the molecular targets compared to other tested compounds.

Synthesis and Characterization of Novel Biological Active Material with Aroyl Urea

This article used thiosemicarbazide and para-pyridinecarboxylic acid to carry out reaction and synthesized 5-(4-pyridyl)-2-amino-1,3,4-thiadiazole, and then reacted with benzoyl isocyanate to synthesize a new type of urea biological active meterial. The structure of the target compound was confirmed by IR, 1H NMR and elemental analysis. The preliminarily biological activity tests show that the target compound has an activity as plant growth regulator, it’s activity as auxin is 19.3% and it’s activity as cytokinin is 27.4%.

Synthesis and Bioactivity of N-Benzoyl-N'-[5-(2'-substituted phenyl)-2-furoyl] Semicarbazide Derivatives

In order to find novel chitin synthesis inhibitors (CSIs) with good activity, benzoylphenylurea, a typical kind of CSIs, was chosen as the lead compound and 15 novel derivatives containing furan moieties were designed by converting the urea linkage of benzoylphenylureas into a semicarbazide and changing the aniline part into furoyl groups. The title compounds were synthesized by the reaction of substituted benzoyl isocyanates with 5-(substituted phenyl)-2-furoyl hydrazine, and the structures were confirmed by IR, 1H-NMR, elemental analysis and single crystal X-ray diffraction analyses (compound E2). The bioassay results indicated that the title compounds exhibit good insecticidal activity, especially towards Plutella xylostella L., but had lower fungicidal activity. Inspiringly, the title compounds possessed obvious anticancer activity against human promyelocytic leukemic cell line (HL-60), and some of the title compounds also had activity against human hepatocellular carcinoma cell line (Bel-7402), human gastric carcinoma cell line (BGC-823), and human nasopharyngeal carcinoma cell line (KB). The results indicated that the linkage in the lead compounds was important to the bioactivity and spectra. The modification on the urea linkage is an effective strategy to discover new pesticide and drug candidates.

Theoretical Study on the Reaction Mechanism between 6-Benzyl-6-azabicyclo[2.2.1]hept-2-ene and Benzoyl Isocyanate to Urea and Isourea

Reaction mechanisms of the 6-benzyl-6-azabicyclo[2.2.1]hept-2-ene with benzoyl isocyanate have been investigated using density functional theory (DFT) at the B3LYP/6-31G(d,p) level of theory. The reaction proceeding along six competitive channels includes two categories. That is, two channels are formally [3,3]-sigmatropic rearrangements and four channels are [4+2] cycloadditions. For urea, the formally [3,3]-sigmatropic rearrangement channel and the [4+2] cycloaddition channels are competitive since they have similar barriers. However, the [4+2] cycloaddition channels are energetically favorable pathways to lead to isourea, with the highest barrier of 12.77 kcal/mol. These polar Diels-Alder (P-DA) reactions are controlled by the charge transfer (CT) at the transition states. Moreover, the main products of this reaction include urea and isourea. Furthermore, difference of two new bond lengths at transition states indicate that the [4+2] cycloadditions in this reaction are asynchronous processes, which is in good agreement with the experiment.

Facile One‐Pot Synthesis of Oxazolidin‐2‐ones from Phenyl 2‐Hydroxyalkyl Selenides

A novel, convenient, efficient, three‐step, one‐pot synthesis of 2‐oxazolidinones from phenyl 2‐hydroxyalkyl selenides was developed. Using this methodology, 2‐oxazolidinones are obtained in good yields (76–85%) by reaction of phenyl 2‐hydroxyalkyl selenides with benzoyl isocyanate and subsequent oxidation/cyclization, followed by hydrolysis with hydrochloric acid solution.

A Facile One-pot Solid-phase Synthesis of Oxazolidin-2-ones Using Polymer-supported 2-hydroxyalkyl Selenide Reagent

A simple, efficient and environmentally friendly procedure for one-pot solid-phase synthesis of 2-oxazolidinones in moderate to good yields by reaction of polystyrene-supported 2-hydroxyalkyl selenide with benzoyl isocyanate and subsequent oxidation/cyclisation-hydrolysis using a selenium traceless linker strategy is described.

Carboxyketenes from 4-Hydroxy-1,3-oxazin-6-ones and Meldrum's Acid Derivatives

New 4-hydroxy-1,3-oxazin-6-ones 8 and 16 were prepared from chlorocarbonyl(phenyl)ketene and amides. The flash vacuum thermolysis (FVT) reactions of these compounds and the 4-methoxy derivative 17 were investigated by Ar matrix isolation IR spectroscopy and online mass spectrometry including MS/MS analysis. Carboxy(phenyl)ketene 10 is formed as the major product by thermal fragmentation of 4-hydroxy-1,3-oxazin-6-one 8. This takes place via the unstable 6-hydroxy tautomer 9. Another tautomer, the 5H-isomer 12, leads to the formation of benzoyl isocyanate 13 as a minor product together with phenylketene 14. Carboxy(phenyl)ketene 10 remains detectable at high FVT temperatures but undergoes thermal decarboxylation to phenylketene 14. The same carboxy(phenyl)ketene 10 is also produced in significant amounts by FVT of 5-phenyl-Meldrum's acid 18 via the unstable enol tautomer 19. A small amount of the unsubstituted carboxyketene 20 is observable on FVT of Meldrum's acid 1 itself.

Synthesis of Highly Substituted Ureas and Thioureas Through 1,3‐Diaza‐Claisen Rearrangements.

AbstractFor Abstract see ChemInform Abstract in Full Text.

The first simple and efficient synthesis of the unusual dipeptide part of Phomopsin A

A practical high yielding synthesis of the key halogenated dipeptide part of Phomopsin A 2 is reported. The key steps are a selective Heck coupling, a Sharpless asymmetric dihydroxylation in PEG and a benzoyl isocyanate mediated synthesis of dehydrovaline.

Synthesis of highly substituted ureas and thioureas through 1,3-diaza-Claisen rearrangements

Isocyanates and isothiocyanates that are not activated by an electron withdrawing group react with azanorbornenes in benzene at reflux to afford ureas and thioureas through the corresponding 1,3-diaza-Claisen rearrangements. At higher temperatures, a triazinone byproduct is observed. Isocyanates and isothiocyanates that are activated by an electron-withdrawing group react at room temperature to give the corresponding ureas and thioureas. The reactions of the activated isocyanates and isothiocyanates are also accompanied by the formation of isoureas and isothioureas. Interestingly, while benzoyl isocyanate reacts with N-benzyl azanorbornene at room temperature to give a 2:1 mixture of urea to isourea, in benzene at reflux the only product observed is the urea. A crossover experiment rules out the possibility that the products are formed through a retro-Diels–Alder, [4+2] cycloaddition sequence instead of a 1,3-diaza-Claisen rearrangement. Competition experiments between isocyanates and isothiocyanates with limiting azanorbornene indicate that isothiocyanates react faster to give the rearrangement product. Since isocyanates are shown to be more electrophilic, these data are consistent with a fast addition step and a rate-determining rearrangement step.

Decomposition of N′‐Benzoyl‐N‐nitrosoureas in Aqueous Media

AbstractThe decomposition of N′‐benzoyl‐N‐methyl‐N‐nitrosourea (BMNU) in aqueous media over the 0−14 pH range has been studied. In basic and neutral media (6 < pH < 14) the reaction proceeds through abstraction of the acidic proton of BMNU (pKa = 7.8) and subsequent decomposition of the conjugate base of the thus formed nitrosourea, via an intermediate benzoyl isocyanate. Support for this mechanism is provided by the presence of N,N′‐dibenzoylurea in the final reaction mixtures, as the result of the trapping of benzoyl isocyanate with benzamide generated from hydrolysis of the former. The hydrolysis of BMNU takes place through three competitive pathways: spontaneous decomposition of the conjugate base of BMNU, and buffer‐catalyzed and hydroxide ion catalyzed water addition to the carbonyl group of the deprotonated nitrosourea. N′‐Benzoyl‐N,N′‐dimethyl‐N‐nitrosourea (BDMNU), a benzoyl nitrosourea lacking the acidic proton of BMNU, is hydrolyzed in basic media by attack of hydroxide ion on the carbonyl group of the urea. In acid media (0 < pH < 6), BMNU gives only deamination products, differing from the reported behavior of other N‐nitroso compounds and of the isoster nitrosoguanidine, in which denitrosation is almost quantitative. The reaction is acid‐catalyzed in the 0−2.5 pH range and pH‐independent in the 3−5 pH range. The presence of general acid catalysis (α = 0.60), the absence of nucleophilic catalysis, and the thermodynamic activation parameters for the reaction support the mechanism proposed in the literature for the deamination of N‐nitrosoureas in acidic media. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

Solid-phase synthesis of complex oligosaccharides using a novel capping reagent.

Solid-phase-supported oligosaccharide synthesis of a core N-glycan tetrasaccharide and of a trisaccharide containing the Galili antigen is reported. The synthesis is based on a hydroxymethylbenzyl benzoate spacer-linker system attached to the Merrifield resin, O-Fmoc-protected O-glycosyl trichloroacetimidates as glycosyl donors, and benzoyl isocyanate as a capping reagent for low-reactivity hydroxy groups. In this way, the target molecules could be efficiently obtained with little byproduct formation, and hence final purification was convenient.

CHLOROSULFONATION OF SOME CRISSCROSS CYCLOADDUCTS FROM ISOCYANATES AND DIARYL AZINES

Reaction of chlorosulfonyl isocyanate (1) with arylaldehyde azines (7) gave the 2:1 crisscross adducts (8);attempts to prepare a disulphonamide of 8a gave only a mixture of the monosulfamide 9 and the diureide 10. The latter with trichloromethanesulfenyl chloride afforded the derivative 12a. and with chlorosulfonic acid hydrazinodicarbonamide (11). The azine 7a with benzoyl isocyanate (2) gave the expected crisscross adduct 13. With thiobenzoyl isocyanate (3) however, both 7a and 7d gave the 1: 1 adducts (14). whereas 7c gave a different 2: 1 adduct (15). Treatment of 14a with 1 gave the ureide 16. With both methyl isocyanate (4) and phenyl isocyanate (S), 7a gave the expected crisscross adducts (17a and b), and 7c with 5 similarly gave 17c. When 7a was treated with 1 followed by aqueous potassium iodide, the diureide (10) was formed; concentrated nitric acid converted 10 into the triazolenone (18). Treatment of 18 with chlorosulfonic acid-thionyl chloride gave the sulfonyl chloride (19) which was characterised as the sulfonamides (20 a-d). Diarylsulfamoyl azines (21 a-f) with 1 and potassium iodide, gave the diureides 22 a-f. 4-Methoxy-3-sulfamoylbenzaldehydeazines (23 a-c) reacted with 3 to give the 1: I adducts 24 a-c, while 4-chlorosulfonylphenyl isocyanate (6) with benzaldehyde azine (7a) gave the bis-chlorosulfonyl adduct (25a). characterised as the diethylsulfonamide 25b. Attempted chlorosulfonation of the tetraphenyl cycloadduct 17b did not give the tetrasulfonyl chloride (although the reaction was successful with the more reactive rnethoxy adduct 17c); the tetrasulfonyl chloride (26a) was converted into 3 sulfonamides (26 b-d). The unsymmetrically-substituted diaryl azines (27) reacted with 1 and potassium iodide to yield the diureides 28 a-f. Analogous cycloadditions of 1 with several keto azines were unsuccessful. Selected compounds will be screened for medicinal and pesticidal activity; compounds 9,10 and 12a showed fungicidal activity against barley powdery mildew.

N-(3-Phenyl-2-propinoyl)benzamide

During the synthesis of a series of carboximides using acyl isocyanates [1], the title compound 3 was synthesised as a model compound from benzoyl isocyanate (1) and lithium phenylacetylide (2).[...]

High-pressure [2 + 2]cyloaddition of acyl isocyanates to glycals

Abstract Isocyanates derived from uretanes 4, s and benzamides 6, 7 react with di-O-benzyl-D-arabinal 3 under 12 kbar pressure to afford the corresponding cycloadducts with high stereoselectivity. Alkoxycarbonyl isocyanates 4 and 5 from [2 + 2]cycloadducts almost exclusively, where benzoyl iSocyanates produce 1:1 mixtures of [2 + 21 and [4 + 2]cycloadducts.

2′‐Deoxyisoguanosine and Base‐Modified Analogues: Chemical and Photochemical Synthesis

AbstractThe synthesis of 2′‐deoxyisoguanosine (2), and the pyrrolo[2,3‐d]pyrimidine and pyrazolo[3,4‐d]pyrimidine 2′‐deoxyribonucleosides 3 and 4 is described. Condensation of the imidazole precursor 5 with benzoyl isocyanate followed by reaction with ammonia gave 2. Its N(7) regioisomer was obtained from 6. Compound 2 was also prepared by the photochemically induced conversion of 2‐Chloro‐ and 2‐bromopurine 2′‐deoxyribofuranosides 9a and 10, respectively, in aqueous solution, The photo reaction was further used for the synthesis of the compounds 3 and 4 starting with the amino‐chloro‐2′‐deoxynucleosides 9b and 9c, respectively.

Pyrazolo[3,4-d]pyrimidine analogues of isoguanine

Abstract 4-Amino-1-phenyl-5H-pyrazolo[3,4-d]pyrimidin-6-one (5a) was synthesized in 68% yield in a one pot reaction involving the condensation of 5-amino-1-phenylpyrazole-4-carbonitrile with benzoyl isocyanate followed by an annulation with ammonia.

ChemInform Abstract: Rapid Synthesis of β‐Hydroxy‐α‐amino Acids, such as L‐Threonine, β‐Hydroxyphenylalanine, and β‐Hydroxyleucine, via an Application of the Sharpless Asymmetric Epoxidation.

AbstractThe 1‐substituted allylic alcohols (I) are subjected to enantioselective Sharpless oxidation, followed by coupling with benzoyl isocyanate (II) and rearrangement, to form the chiral oxazolidinones (VI).

ChemInform Abstract: A Facile Synthesis of N′‐Benzoyl‐N‐thiophosphorylureas.

AbstractThe thiophosphorylureas (III) mentioned in the title are prepared by coupling the thiophosphoric amide (I) with benzoyl isocyanate (II), generated from benzamide and oxalyl chloride.