Isothiocyanates heterocyclics

The reaction of 2-aminothiazoles with alkyl isothiocyanates yields 2-thiazolylthioureas (30.3, 490), otherwise usually obtained by direct heterocyclization (Chapter II. Section II.4). Other synthetic methods... 

The reaction of the enamines of cyclic ketones with alkyl isocyanates, acyl isocyanates, phenyl isothiocyanates, and acyl isothiocyanates has also been reported 112). The products are the corresponding carboxamides. The products from the isothiocyanates have been utilized as intermediates in the preparation of various heterocyclic compounds 113). 

Reactions of unsaturated carbanions with isothiocyanates in synthesis of heterocycles 99JHC1469. 

Free amino acids can be derivatized with isothiocyanates to phenyl- or methyl-thiohydantoin derivatives. The thiohydantoins can be separated on a CSP with poly-[Af-acryloyl-L-phenylalanine ethylester] (Chiraspher ) as a chiral selector [25]. This CSP offers a known selectivity for many five-membered heterocyclic rings. 

The second approach for the synthesis of 2-amino-3-hydroxycarboxylic acids starts with a chiral isothiocyanate which is added, via the tin enolate, to aldehydes. The initially formed adducts are immediately derivatized to the heterocycles, from which. yj 7-2-amino-3-hy-droxycarboxylic acids result after a three-step procedure. The diastereomeric ratios of the intermediate bis-heterocyclic products range from 93 7 to 99 1 (desired isomer/sum of all others)104. 

Other thietane derivatives have been obtained by isomerization of nitrogen-containing heterocycles. The reaction of an acyl isothiocyanate (RCONCS) with diphenyldiazomethane gave 20 and this isomerized in solution to the tetraphenyl-3-thietanone 21 <96BSB253>. Additionally, the isoxazolidine 22 was converted into 23 by the action of trimethylsilyl iodide and zinc iodide <96H1211>. 

Glutaconaldehyde anion serves as an interesting intermediate for the synthesis of heterocyclic compounds. The parent pyrylium perchlorate has been prepared from glutaconaldehyde and 70% perchloric acid in ether at -55°.° The reaction of glutaconaldehyde anion with alkyl and aryl isothiocyanates and... 

A recent paper from Katritsky summarises all the preparations of achiral dissymmetrical thioureas and proposes a new one, based on l-(alkyl/arylthio-carbamoyl)benzotriazoles, which act as masked isothiocyanates. As described in the previous section, other N-heterocyclic derivatives can be used instead... 

Reactions of Heterocyclic N-Oxides with Trimethylsilyl Cyanide, Trimethylsilyl Azide, Trimethylsilyl Isothiocyanate, and Trimethylsilyl Halides... 

Ferndndez-Bolanos JG, Lopez 6 (2007) Heterocycles from Carbohydrate Isothiocyanates. 7 67-100... 

The synthesis of (V-heterocyclic isothiocyanates has been a difficult challenge due to their propensity to oligomerize by autocatalysis. In an attempt to alleviate this issue, silver thiocyanate was used in a novel synthesis of 4-quinolyl isothiocyantes <06TL2161>. Reaction of 4-chloroquinoline with silver thiocyanate in refluxing anhydrous toluene for 12 h results in the desired product in quantitative yields and excellent purity. 

Reaction of isothiocyanate with amine gives the corresponding thioureas. Many reports are appeared.102 111 The thiourea derivatives have been prepared by reactions of isothiocyanates with arylamines (Scheme 39) and reacted with some substrates to afford heterocyclic compounds, such as 2-amino-4//-ben-zothiazine, 1,3-thiazine, 1,3-thiazinone and l,3-thiazolidin-4-one.112 115... 

Substituted derivatives of l-(tetrahydrobenzo[b]thiophen-2-yl-3-carboxylate)-5-phenyl-6-thio-l,2,4-triazin-4-one have been synthesized by heterocyclization reactions of different hydrazones obtained from 2-amino-tetrahydrobenzo[b]thiophene-3-carboxylate with phenyl isothiocyanate <00PS275>. Reaction of 5-methyl isothiosemicarbazide with a-amino acid vicinal tricarbonyl reactive substrates 1 and 2 yields 1,2,4-triazine substituted a-amino acids, as an equimolar mixture of regioisomers 3a/3b and 4a /4b, respectively <00JCS(P1)299>. 

Complexes of picolinamide with lanthanide perchlorates, nitrates, and isothiocyanates have been isolated by Condorelli et al. (59). All these complexes show changes in the stoichiometry on going from La(III) to Lu(III). The ligand acts as bi-dentate with the oxygen of the amide group as well as the heterocyclic nitrogen coordinating to the metal (Structure I). While the anions in the perchlorate complexes are not coordinated to lanthanide ions, those in the nitrate and isothiocyanate complexes are coordinated. 

The carbon in the isothiocyanate grouping is highly susceptible to nucleophilic attack by the peptide s free amino group. Overall addition to the C=N creates a thiourea derivative. Making the conditions strongly acidic then promotes nucleophilic attack by the sulfur of the thiourea on to the carbonyl of the first peptide bond, producing a five-membered thiazoline heterocycle. Proton loss occurs from the nitrogen, and this creates an intermediate that is equivalent to the addition product in simple acid-catalysed amide... 

Solomon DM, Rizvi RK, Kaminski JJ (1987) Observations on the reactions of isocyanoacetate esters with isothiocyanates and isocyanates. Heterocycles 26(3) 651-674... 

A second type of synthetic route to meso-ionic l,3,4-thiadiazol-2-imines (247) is based on the acid-catalyzed reaction of N-thioacylhydrazines (232) with aryl isothiocyanates (Ar-NCS). " This reaction yields the s ts (248) as precursors of the meso-ionic heterocycles (247). An interesting variant upon this route involves the reaction between IV-thioacylhydrazines (232) and acyl isothiocyanates (RCO-NCS). This leads to the meso-ionic heterocycles 247, R = COzEt, CONMej, COMe, COCMe, COAr, and SOjPh. The investigation of these compounds by X-ray photoelectron spectroscopy is a good example of the application of this physical method for the examination of meso-ionic compounds. 

Robert and co-workers (239,240) discovered novel conversions of 2-amino-1,3-dithiolium-4-olates (348) into other mesoionic heterocycles. For example, reaction of 348 with carbon disulfide, phenyl isocyanate, or phenyl isothiocyanate affords l,3-dithiolium-4-thiolates (349), l,3-thiazolium-4-olates (350), and 1,3-thiazolium-4-thiolates (351), respectively. Some of these reactions proceed via the ring-opened ketene tautomer of 348 (240). 

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