Ethoxycarbonyl Isothiocyanate Research Articles

Conformations and structures of ethoxycarbonyl isothiocyanate revealed by rotational spectroscopy

The ethoxycarbonyl isothiocyanate has been investigated by using supersonic jet Fourier transform microwave spectroscopy. Two sets of rotational spectra belonging to conformers TCC (with the backbone of C−C−O−C, C−O−C=O, and O−C(=O)−NCS being trans, cis, and cis arranged, respectively) and GCC (gauche, cis, and cis arrangement of the C−C−O−C, C−O−C=O, and O−C(=O)−NCS) have been measured and assigned. The measurements of 13C, 15N and 34S mono-substituted species of the two conformers have also been performed. The comprehensive rotational spectroscopic investigations provide accurate values of rotational constants and 14N quadrupole coupling constants, which lead to structural determinations of the two conformers of ethoxycarbonyl isothiocyanate. For conformer TCC, the values of Pcc keep constant upon isotopic substitution, indicating that the heavy atoms of TCC are effectively located in the ab plane.

Fused Heterocyclic Systems with an s-Triazine Ring. 34. Development of a Practical Approach for the Synthesis of 5-Aza-isoguanines.

Purine isosteres present excellent opportunities in drug design and development. Using isosteres of natural purines as scaffolds for the construction of new therapeutic agents has been a valid strategy of medicinal chemistry. Inspired by the similarity to isoguanine, we attempted to develop a practical method for the preparation of 5-aza-isoguanines. Several synthetic approaches were explored to establish a robust general protocol for the preparation of these compounds. The significant difference in the reactivity of the C-5 and C-7 electrophilic centers of 1,2,4-triazolo[1,5-a][1,3,5]triazines (5-azapurines) towards nucleophiles was demonstrated. The most practical and general method for the preparation of 5-aza-isoguanines involved a regioselective reaction of ethoxycarbonyl isothiocyanate with a 5-aminotriazole. The intramolecular ring closure of the resulted product followed by the S-methylation afforded 7-methylthio-2-phenyl-1,2,4-triazolo[1,5-a][1,3,5]triazin-5-one, which could be effectively aminated with various amines. The resulted 5-aza-isoguanines resemble a known purine nucleoside phosphorylase inhibitor and could be interesting for further investigations as potential anticancer agents.

Regioselective (thio)carbamoylation of 2,7-di-tert-butylpyrene at the 1-position with iso(thio)cyanates.

It has been found that 2,7-di-tert-butylpyrene reacts with aliphatic iso(thio)cyanates in the presence of trifluoromethanesulfonic acid to exclusively afford the corresponding 1-substituted (thio)amides in high yields. For aromatic iso(thio)cyanates the reaction is less regioselective, although substitution at the 1-position prevails. For ethoxycarbonyl isothiocyanate, apart from the 1-substituted thioamide, 1,8-disubstituted thioamide and 2,7-di-tert-butylpyrene-1-carbonitrile are formed (especially at longer reaction times).

Establishment of highly sensitive and selective fluorescent sensor for Fe3+ based on a post-synthetic modification of metal-organic framework

A post-synthetic modification method was developed to prepare fluorescent metal organic frameworks by the covalent interaction of ethoxycarbonyl isothiocyanate with amine functionalized UMCM-4. X-ray diffraction spectrometry, X-ray photoelectron spectrometry, elemental analysis, Fourier-transformed infrared spectroscopy, nuclear magnetic resonance spectrometry, thermogravimetric analysis/derivative thermogravimetry analysis, and nitrogen sorption isotherms were employed to characterize the modified metal organic frameworks. With high emission efficiency and excellent fluorescence stability, the sensing properties of Fe3+ were studied. Possible mechanisms of energy and electron transfers between the target and the fluorescent probe were demonstrated. Effects of response time, Fe3+ concentration, and other metal ions on the fluorescence intensity were also studied.

Synthesis and carbonic anhydrase I, II, IX and XII inhibition studies of 4-N,N-disubstituted sulfanilamides incorporating 4,4,4-trifluoro-3-oxo-but-1-enyl, phenacylthiourea and imidazol-2(3H)-one/thione moieties

A series of sulfonamides incorporating the sulfanilamide (SA) scaffold were prepared. Reaction of the 4-amino moiety of SA with benzyl chlorides or substituted bromoacetophenones afforded the 4-mono-alkylated derivatives which were then reacted with 1,1,1-trifluoro-4-isobutoxybut-3-en-2-one leading to a series of 4-N,N-disubstituted SAs. The key intermediates were also reacted with ethoxycarbonyl isothiocyanate leading to thioureas or were cyclized in the presence of potassium cyanate/isothiocyanate to the corresponding imidazol-2(3H)-one/thiones. The new compounds were tested as inhibitors of four carbonic anhydrase (CA, EC 4.2.1.1) isoforms, the cytosolic CA I and II, and the transmembrane, tumor-associated CA IX and XII. These sulfonamides were ineffective CA I and II inhibitors but were nanomolar CA IX and XII inhibitors, making them of interest as clinical candidates for antitumor/antimetastasis applications.

Synthesis of ethoxycarbonyl isothiocyanate by orthogonal design

Using Schiff base as a phase transfer catalyst, ethoxycarbonyl isothiocyanate was synthesized by reacting ethyl chloroformate with sodium thiocyanate. In order to get the best synthetic technology, an orthogonal test (L9(34)) was applied. The results show that reaction temperature, reaction time, content of catalyst and molar ratio of sodium thiocyanate to ethyl chloroformate are the main factors influencing the yield. The four factors chosen for the present investigation are based on the results of a single-factor test. The optimum synthetic technology is determined as follows: reaction temperature 35 °C, reaction time 3 h, the content of catalyst (molar fraction based on ethyl chloroformate) 1.5% and molar ratio of sodium thiocyanate to ethyl chloroformate 1.1. Under the optimized synthetic technology, the experimental yield reaches 96.8%.

-OXOANILIDE AS BUILDING BLOCKS IN HETEROCYCLIC SYNTHESIS: A NEW SYNTHESIS OF POLYFUNCTIONALLY SUBSTITUTED PYRIDINES, PYRANS AND PYRIMIDINES

β-Oxoanilide 1 reacted with acetyl isothiocyanate and ethoxycarbonyl isothiocyanate to givepyridine derivatives 6a,b and pyrimidinethiol 8 respectively. While with arylidine malononitrile gave the pyran derivative 12. Similarly, treatment of 1 with arylidine cyanoacetamide or arylidine cyanothioacetamide afforded the pyridine derivatives 13a,b, 14a,b respectively. Condensation of 1 with aromatic aldehyde obtained the cyclohexenones 19a-c. The reaction of 1 with a mixture of aromatic aldehyde and urea or thiourea gave the pyrimidine derivatives 23a,b. Treatment of compound 1 with arylidine acetophenone yield the cyclohexene derivatives 26a,b. Reaction of 1 with a mixture of ethyl cyanoacetate and sulfur yield the thiophene derivative 27. Which was reacted with formamide, potassium thiocyanate and hydrazine to afford the thienopyrimidines 28, 29 and the hydrazide derivative 30. respectively.

Preparation and Chelating Properties of Polystyrene Modified Ethoxycarbonyl Thiourea Resin

A novel polystyrene modified ethoxycarbonyl thiourea resin(PSETU) was synthesized by polymer grafting of aminated polystyrene and ethoxycarbonyl isothiocyanate. The adsorption capacities of PSETU follow the order: Au(III) > Cu(II) > Zn(II) > Ni(II) > Fe(III) > Ca(II) ≈ Mg(II). The adsorption capacity for Au(III) increases with the increase of contact time, temperature and initial concentration of Au(III). The adsorption data fit Boyd’s diffusion equation of liquid film, Langmuir adsorption isotherm and Freundlich adsorption isotherm. The maximum adsorption capacity of PSETU calculated by Langmuir isotherm equation is 3.485 mmol/g, and the separation factors of PSETU for Au(III)-base metal ions are above 380. According to XPS results, the functional atoms of PSETU coordinate with Au(III) during the adsorption process.

Triazine-fused β-carbolines: a facile three-step, one-pot synthesis of novel 2-alkyl(aryl)amino and 2-dialkylamino-7H-[1,3,5]triazino [1',2':1,6]pyrido[3,4-b]indol-4-ones

A straightforward approach to novel fused β-carbolines namely (1,3,5)triazino (1',2':1,6)pyrido(3,4-b)indol-4-ones is presented. The construction of these compounds was achieved by one-pot synthesis involving condensation of 3-amino-β-carbolines with ethoxycarbonyl isothiocyanate followed by amination of the resulting thioureas and finally thermal ring closure of the resulting guanidines which allowed access to the unreported title heterocycles.

The Synthesis of Novel 2,4,6-Trisubstituted 1,3,5-Triazines: A Search for Potential MurF Enzyme Inhibitors

A series of new 2,4,6-trisubstituted 1,3,5-triazines, possessing a variety of substituents (-OH, -SH, -OMe, -Cl, -HNR, -SR and amino acid moieties), were synthesized and evaluated for the inhibition of the bacterial peptidoglycan biosynthesis enzyme MurF. Ethoxycarbonyl isothiocyanate successfully reacted with a variety of amidines, enabling an approach to 6-substituted-4-thioxo-1,3,5-triazin-2-ones. Also, a representative set of 2-thio-, 2-amino-, and 2-oxo-substituted 1,3,5-triazines was synthesized by the S N Ar reaction, employing 2,4,6-trichloro-1,3,5-triazine and 2-chloro-4,6-dimethoxy-1,3,5-triazine as the starting materials. One compound displayed notable inhibitory activity against MurF from Escherichia coli.

Synthesis and reactions of p-hydroxythiobenzamides

Ethoxycarbonyl isothiocyanate reacted with phenols in a nitromethane solution of aluminum chloride to yield the appropriate 4-hydroxy-N-ethoxycarbonylthiobenzamides. In the reaction with dinucleophiles they gave heterocyclic compounds which were subsequently functionalized on the hydroxy group. The reaction of p-hydroxythiobenzamides with carbamoyl chloride, chlorides of α,β-unsaturated carboxylic acids, and isocyanates yielded the corresponding O-acylated products.

Substituted 2-Methylene-1,3-oxazolidines, -1,3-thiazolidines, -1,3-benzothiazines, -1,3-oxazines, and Substituted Imidazopyrimidinediones from Cl(CH2)nNCO and Cl(CH2)nNCS and Active Methylene Compounds

The reaction of omega-chloroalkyl isocyanates Cl(CH2)nNCO (n = 2 (2), 3 (4)) and isothiocyanate Cl(CH2)2NCS (3) with active methylene compounds CH2YY' 1 in the presence of Et3N or Na give 2-YY'-methylene-1,3-oxazolidines, (E,Z)-1,3-thiazolidines, and 1,3-oxazines from 2, 3, and 4, respectively. 2-(Chloromethyl)phenyl isocyanate 8 gives with 1 the corresponding benzo-oxazines. Ethyl 2-isothiocyanatobenzoate 10 gives the corresponding benzothiazolinone, whereas the analogous isocyanate 12 gives noncyclic enols. Ethoxycarbonyl isothiocyanate 14 gives an open-chain thioenol or an enol-thioamide. The cyanoamides CH2(CN)CONHR, R = H, Me, CHPh2, give with Et3N and 2 the bicyclic imidazopyrimidinediones 16, derived from two molecules of 2, but with their preformed Na salt they give the 1,3-oxazolidines. Reaction of cyanoacetamide with 3 in the presence of Na gave a tricyclic triaza(thia)indacene, derived from two molecules of 3. A reaction mechanism involving an initial attack of the anion 1- on the N=C=X (X = O, S) moiety gives an anion 18, which cyclizes intramolecularly and after tautomerization gives the mono-ring heterocycle. With the cyanoamides, the N- site of the ambident ion 18 attacks another molecule of 2 giving the anion 20, which by intramolecular attack on the CN, followed by expulsion of the Cl- gives the bicyclic 16 after tautomerization.

Ferrocenecarbothioamide and N-ethoxycarbonylferrocenecarbothioamide: Synthesis, structure and application in synthesis of 2,4-diferrocenylthiazole

Ferrocenecarbothioamide ( 1) and its N-ethoxycarbonyl derivative ( 2) were synthesised by a Friedel–Crafts type reaction of ferrocene with potassium thiocyanate and ethoxycarbonyl isothiocyanate, respectively, in a strongly acidic medium. The X-ray structure of 1 was determined and shows conjugation between the ferrocene moiety and the thioamido group. Compound 1 reacts with chloroacetylferrocene affording 2,4-diferrocenylthiazole, whose structure was determined by X-ray diffraction and electronic properties studied by cyclic voltammetry.

TMEDA‐Catalyzed Synthesis of N‐Aryl‐N′‐ethoxycarbonyl Thiourea and Arene (or Polymethylene)‐bis‐ethoxycarbonylthiourea Derivatives.

AbstractFor Abstract see ChemInform Abstract in Full Text.

TMEDA-CATALYZED SYNTHESIS OF N-ARYL-N′-ETHOXYCARBONYL THIOUREA AND ARENE (OR POLYMETHYLENE)-BIS-ETHOXYCARBONYLTHIOUREA DERIVATIVES

A novel and efficient method for synthesis ethoxycarbonyl isothiocyanate and ethoxycarbonyl thioureas catalyzed by TMEDA is reported. A series of N-aryl-N′-ethoxycarbonyl thioureas and arene (or polymethylene)-bis-ethoxycarbonyl thiourea derivatives have been synthesized in good-to-excellent yields via this method at room temperature.

Reaction of tetraazathiapentalene and thiadiazolopyrimidine derivatives with heterocumulenes: Cycloaddition and elimination reactions via hypervalent sulfur intermediates

AbstractTetraazathiapentalene derivative 1 reacts with heterocumulenes such as diphenylketene (2) and 2‐pyridylisothiocyanate (5) to give heterocycles 3, 6 and 7 with elimination of methylisothiocyanate. The reactions of thiadiazolopyrimidine derivatives 8a‐b with ethoxycarbonyl isothiocyanate (9) and carbon disulfide (11) gives heterocycles 10 and 12 via thermal decomposition of 1:1 cycloadducts C and D which have a hypervalent sulfur. The mechanistic and reactivity features of these reactions are described.

Formation of a Stable Adduct of Ethoxycarbonyldithiocarbamic Acid and a Dimer of Ethoxycarbonyl Isothiocyanate

The reaction of ethoxyxcarbonyl isothiocyanate with water in the absence of a solvent has yielded the new compound [EtO2CN=CS2C{N(H)CO2Et}{S2CN(H)CO2Et}] (1) in 76% yield that has been isolated in a crystalline form that con-tains one equivalent of ethoxyxcarbonyl isothiocyanate. Compound 1 can be viewed as an adduct of a dimer of EtO2CN=C=S and the dithiocarbamic acid 2. Compound 1 dissociates in solution to yield 2 and free ethoxyxcarbonyl isothiocyanate. Compound 2 can be isolated chromatog-raphically, but it is slowly oxidized when allowed to stand in the open air to form the thiuram disulfide 3. Compounds 1 and 3 were characterized crystallographically. Compound 1 contains an imino-substituted dithietane ring with a dithiocarbamate substitutent bonded to one of the ring carbon atoms. Compound 3 is a thiuram disulfide which has C2 crystallographic symmetry.

Formation of a Stable Adduct of Ethoxycarbonyldithiocarbamic Acid and a Dimer of Ethoxycarbonyl Isothiocyanate

The reaction of ethoxyxcarbonyl isothiocyanate with water in the absence of a solvent has yielded the new compound [EtO2CN=CS2C{N(H)CO2Et}{S2CN(H)CO2Et}] (1) in 76% yield that has been isolated in a crystalline form that con-tains one equivalent of ethoxyxcarbonyl isothiocyanate. Compound 1 can be viewed as an adduct of a dimer of EtO2CN=C=S and the dithiocarbamic acid 2. Compound 1 dissociates in solution to yield 2 and free ethoxyxcarbonyl isothiocyanate. Compound 2 can be isolated chromatog-raphically, but it is slowly oxidized when allowed to stand in the open air to form the thiuram disulfide 3. Compounds 1 and 3 were characterized crystallographically. Compound 1 contains an imino-substituted dithietane ring with a dithiocarbamate substitutent bonded to one of the ring carbon atoms. Compound 3 is a thiuram disulfide which has C2 crystallographic symmetry.

On the reaction of isothiosemicarbazides with heterocumulenes. Part I

AbstractIsothiosemicarbazides 2 react with acyl isothiocyanates under addition‐cyclization to yield 1,3,4‐thiadiazoline‐2‐imines 3 as well as the isomeric 2‐amino‐substituted 1,3,4‐thiadiazolium‐5‐acylaminides 3′. In a similar manner the 2‐hydrazino‐substituted 1,3‐thiazoline 4 adds ethoxycarbonyl isothiocyanate to give the thiosemicarbazide 5, which undergoes a rearrangement to the 1,3,4‐thiadiazoline‐2‐imine 5′. The [2+2] cycloreversion of 3d involving ethoxycarbonyl iso(thio)cyanate and the thermal induced Dimroth rearrangement of 3′f and h are also discussed.

Novel Imidazoles and Hydantoins Moderately Strained by Incorporation with 2-Azabicyclo[2.2.1]heptene Skeleton

Abstract The reactions of 3-acyl-2-azabicyclo[2.2.1]hept-5-enes with phenyl isocyanate, phenyl isothiocyanate, and ethoxycarbonyl isothiocyanate followed by cyclization reactions under basic conditions respectively provided a hydantoin, a thiohydantoin, and a 1,3-dihydro-2H-imidazole-2-thione incorporated with the azabicyclic skeleton. Treatment of the imidazolethione with Raney nickel gave a phenyl-substituted imidazole fused with 2-azabicyclo[2.2.1]hept-2-ene. The effect of annulation on the 13C NMR of the imidazole ring is discussed.