Reaction of 4,5-diaminopyrimidine and ethyl acetoacetate: Synthesis and chemistry of isomeric dihydropyrimido[4,5-b][1,4] diazepinones

Depending upon reaction conditions, 4,5-diaminopyrimidine and acetoacetic ester gave a variety of condensation products, including the two isomeric dihydropyrimido[4,5-b][1,4]-diazepinones. Under conditions leading to bicyclic products, the formation of 1,5-dihydro-4-methyl-2H-pyrimido[4,5-b][1,4]diazepin-2-one ( 2 ) was strongly favored. The isomeric 3,5-dihydro-2-methyl-4H-4-one compound ( 4 ) was best obtained by cyclization of ethyl 3-(4-amino-5-pyrimidylamino)crotonate ( 3 ) under base catalysis. Thermal rearrangement of 2 and 4 proceeded, in each instance, with loss of the isopropenyl moiety and gave 8-purinone. Compound 4 underwent ring contraction under the influence of alkoxide to yield a product which was shown to be the 7-isopropenyl-8-purinone ( 6 ).     

Über die säurekatalysierte Umlagerung von β-Jonon-5,6-epoxid

β-Ionone-5,6-epoxide ( 1 ) undergoes acid-catalyzed ring contraction and enlargement, concurrently, by [1, 2]-alkyl shifts, to give the isomeric cyclopentane derivative 6 and the cycloheptafurane derivative 7 . Spectroscopic and chemical evidence for the structures of 6 and 7 is presented.     

Ring transformation of 5-acylpyrimidines into 4-acylpyrazoles with hydrazine and phenylhydrazine in acidic medium

5-Benzoyl-4-methylpyrimidines 4a,b and 5-acetyl-4-phenylpyrimidines 5a,b reacted with hydrazines in alcoholic acidic medium to give respectively 4-acetyl-3-phenylpyrazoles 7, 9 and 10 and 4-benzoyl-3-methylpyrazoles 6, 8 and 11 . In the reaction with phenylhydrazine, 5-benzoyl-4-methyl-2-methylthiopyrimidine ( 4a ) led exclusively to 4-acetyl-1,3-diphenylpyrazole ( 10 ) as 5-acetyl4-phenyl-2-methylthiopyrimidine ( 5a ) led to 4-benzoyl-3-methyl-1-phenylpyrazole ( 11 ) via the initial formation of phenylhydrazones of pyrimidines 4a and 5a . However, 5-benzoyl-4-methyl-2-phenylpyrimidine ( 4b ) and 5-acetyl-2,4-diphenylpyrimidine ( 5b ) reacted with phenylhydrazine to afford, each of them, a mixture of two isomeric pyrazoles. The mechanism of these ring contraction reactions is discussed.     

A highly selective Bi(OTf)3 mediated fragmentation-contraction of δ-ortholactones. A facile route to functionalized γ-lactones

A very selective method for the formation of γ-lactones from pyranyl ortholactones has been developed which occurs via a fragmentation-acetate migration-ring contraction process. The reaction is very functional group tolerant, providing functionalized γ-lactones as a single isomeric product following the ring contraction. Mechanistic studies indicate the reaction is mediated by triflic acid liberated from Bi(OTf)₃ in a slow and controlled manner providing excellent chemo and regioselectivity. We propose the triflic acid acts as both a proton and a nucleophile source with triflate anion mediating the fragmentation process.     

2-pyrazinylnitrene and 4-pyrimidylnitrene. Ring expansion to 1,3,5-triazacyclohepta-1,2,4,6-tetraene and ring opening to (2-Isocyanovinyl)carbodiimide

Tetrazolo[1,5-a]pyrazine/2-azidopyrazine 9T/9A undergo photolysis in Ar matrix at cryogenic temperatures to yield 1,3,5-triazacyclohepta-1,2,4,6-tetraene 21 as the first observable intermediate, and 1-cyanoimidazole 11 and (2-isocyanovinyl)carbodiimide 22 as the final products. The latter tautomerizes to 2-(isocyanovinyl)cyanamide 23 on warming to 40 K. The same intermediate 21 and the same final products are obtained on matrix photolysis of the isomeric tetrazolo[1,5-c]pyrimidine/4-azidopyrimidine 24T/24A. These photolysis results as well as those of the previously reported thermal ring contraction of (15)N-labeled 2-pyrazinyl- and 4-pyrimidylnitrenes to 1-cyanoimidazoles can all be rationalized in terms of selective ring opening of 21 or nitrine 10 to a nitrile ylide zwitterion 28 prior to formation of the final products, 11 and 22. The results are supported by high-level ab initio and DFT calculations (CASPT2-CASSCF(6,6), G3(MP2), and B3LYP/6-31+G) of the energies and IR spectra of the intermediates and products.     

A ring walk of methylene groups in toluene radical cations. An extension of the toluene-cycloheptatriene rearrangement of aromatic radical cations. Theory and experiment

The minimum energy reaction pathway (MERP) of the toluene-cycloheptatriene radical cation rearrangement (TOL/CHT-rearrangement) has been calculated by the UHF and DFT model at the level UHF/6-311+G(3df,2p)//UHF/6-31G(d) and B3LYP/6-311+G(3df,2p)//B3LYp/6-31G(d), respectively, including the ring walk of the substituent by a 1,2-shift around the aromatic ring. This ring walk corresponds to interconversion of distonic ions and norcaradiene radical cations (the two intermediates of the TOL/CHT-rearrangement) by making and breaking of the external C-C bonds of the cyclopropane moiety of the intermediate norcaradiene structure. For toluene radical cation 1, UHF calculations adequately reproduce earlier results(4) and show, that the ring walk of the CH(3)-substituents requires slightly more energy than formation of the cycloheptatriene radical cation. By the DFT model, the distonic ion, which is formed initially by a 1,2-H shift from CH(3) to the benzene ring, is not stable but the transition state of an interconversion of norcaradiene radical cations along a ring walk of the CH(3) substituent. The activation energy for this ring walk exceeds that for formation of the cycloheptatriene radical cation by c. 30 kJ mol(-1). Thus, isomerization of 1 by a ring walk of the CH(3)-substituent competes with the TOL/CHT-rearrangement likely only for excited 1. The calculation was repeated for the MERPs of a TOL/CHT-rearrangement of para-xylene radical cation 5 and ethylbenzene radical cation 2, yielding basically the same results as for 1. According to the calculation, polar substituents alter significantly the relative energies of the competing routes of isomerization. For benzylcyanide 3 (X = CN), the activation energy for a ring walk of the NC-CH(2)-substituent is distinctly below that of a ring enlargement. For benzyl methyl ether 4 (X = OCH(3)), the distonic intermediate along the UHF-MERP is unusually stable. Further, the 7-methoxy-norcaradiene radical ion is unstable and corresponds to a transition state between isomeric distonic intermediates differing by a 1,2-shift of the side chain. In contrast, the 7-methoxy-norcaradiene radical ion is the only intermediate of the DFT-MERP, and the distonic ion is the transition state for a 1,2-shift of the cyclopropane ring. A ring walk of the CH(3)OCH(2)-substituent is much more favorable than formation of a 7-methoxy-cycloheptatriene radical cation in both MERPs. The findings of the theoretical calculation are substantiated by the mass spectrometric fragmentations of meta- and para-methoxymethylated 1-phenylethanols 8 and 9 and of para-methoxymethyl substituted benzyl ethyl ether 10 and benzyl n-propyl ether 11. Important fragmentation routes of metastable molecular ions of these compounds correspond to elimination of alcohols. Use of deuterated derivatives shows that the elimination occurs by a "false" ortho-effect which requires migration of a ROCH(2)-substituent around the benzene ring. Results of particular interest are obtained for the asymmetric bis-ethers 10 and 11. Here, the MIKE spectra of the molecular ions of deuterated analogs reveal a selective ring walk of the C(2)H(5)OCH(2)- and n-C(3)H(7)OCH(2)-side chain, respectively.     

2-Thioxo-1,3-thiazepan-4-ones,a novel class of cyclic dithiourethanes with a 7-membered ring system

Reaction of isothiocyanates 1 with γ-thiobutyrolactone ( 2 ) in alkaline medium yielded 4-thiocarbamoylthiobutyric acids 3 after acidification, which could be cyclized to the 2-thioxo-1,3-thiazepan-4-ones 6 . Additional reactions were observed with the formation of 6t from p-phenylenediisothiocyanate ( 1s ) and with the formation of 6w from benzyl isothiocyanate ( 1t ). 3-Acetylamino-γ-thiobutyrolactone ( 7 ) could also be used in this reaction yielding the butyric acid derivatives 3u-3w . Cyclization yielded the 1,3-thiazepane derivatives 6x, y which rearranged under ring contraction to the 1,3-thiazinanes 8a, b .     

Recyclization of 2-(3,6-diaryl-2,5-dihydropyridazin-4-yl)-1H-benzimidazoles to 2-[(3,5-diarylpyrazol-4-yl)methyl]-1H-benzimidazoles

2-(3,6-Diaryl-2,5-dihydropyridazin-4-yl)-1H-benzimidazoles undergo a previously unknown type of recyclization of the pyridazine ring to a pyrazole to give 2-[(3,5-diarylpyrazol-4-yl)methyl]-1H-benzimidazoles. It is suggested that the mechanism of this conversion, which includes formation of a secondary enhydrazine group in the diazine ring and its subsequent contraction, occurs after the intramolecular formation and opening of a cyclopropane ring. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 853–861, June, 2008.     

Intramolecular 1,8-hydrogen atom transfer reactions in disaccharide systems containing furanose units

A previously developed 1,8-hydrogen atom transfer (HAT) reaction promoted by 6-O-yl alkoxyl radicals between the two pyranose units in Hexp-(1→4)-Hexp disaccharides has been extended to other systems containing at least a furanose ring in their structures. In Penf-(1→3)-Penf (A) and Hexp-(1→3)-Penf (B) disaccharides, the 1,8-HAT reaction and concomitant cyclization to a 1,3,5-trioxocane ring are in competition with radical β-scission of the C4-C5 bond and formation of dehomologated products. The influence of the stereoelectronic β-oxygen effect on the β-scission and consequently on the 1,8-HAT reaction has been studied using the four possible isomeric d-furanoses. d-xylo- and d-lyxo-derivatives afforded preferentially 1,8-HAT products, whereas d-arabino- and d-ribo-derivatives gave exclusively direct β-scission of the alkoxyl radical. When the 6-O-yl radical is on a pyranose ring, as occurs in Penf-(1→4)-Hexp (C), it has been shown to provide the cyclized products exclusively.     

The synthesis of six‐membered P‐heterocycles with sterically demanding substituent on the phosphorus atom

The ring enlargement of 1‐(2,4,6‐trialkylphenyl)2,5‐dihydro‐1H‐phosphole oxides ( 1 ) via 6,6‐dichloro‐3‐Phosphabicyclo[3.1.0]hexanes ( 2 ) afforded the double‐bond isomers of 1,2‐dihydrophosphinine oxides ( 3 ). Catalytic hydrogenation of the isomeric 1‐(di‐tert‐butyltolyl)‐1,2‐dihydrophosphinine oxides ( 3a ) gave the diastereomers of phosphinane oxide ( 4 ), while that of the 1‐(tri‐isopropylphenyl) isomers ( 5 ) led predominantly to phospholane oxides ( 6 ) formed by ring contraction. © 2001 John Wiley & Sons, Inc. Heteroatom Chem 12:528–533, 2001     

Massenspektroskopische fragmentierungsreaktionen—III : Das scheinbar anomale verhalten von 3-hydroxytetrahydropyransystemen

Tetrahydropyran derivatives may lose C-2 together with a substituent from C-3 accompanied by ring contraction. This explains why, e.g., compounds derived from 3-hydroxytetrahydropyran sometimes fragment in a manner expected for an isomeric tetrahydrofuran system. The prerequisities for this rearrangement and its mechanism are discussed.     

The photochemistry of cyclic nonenolizable α-diketones and ketones influence of remotely positioned sulfide,sulfone, and sulfoxide functionalities

The photochemistry of 3,3,6,6-tetramethyl-1-thiacycloheptane-4,5-dione has been examined along with that of the corresponding S-oxide and S,S-dioxide. The chief photochemical process in the first mentioned compound is ring contraction affording 3,3-dimethyl-1-thia-cyclobutan-2-one, isobutene, and carbon monoxide. In addition a small amount of 3,3,6,6-tetramethyl-1-thiacyclohexan-4-one is formed along with two isomeric unsaturated aldehydes. On independent irradiation this thiacyclohexanone affords the same products as its 7-membered diketone counterpart. Similar products are obtained for the S-dioxides investigated save that the ring contraction process was absent. The S-oxides gave no identifiable products. All the results are rationalized in terms of a generalized mechanism involving biradical intermediates.     

2-(1-Azulyl)ethyl tosylate methylene scrambling in the gas phase. Similarities to solution chemistry

The methylene groups in 2-(1-azulyl)ethyl tosylate are largely scrambled prior to formation of fragment ions in the mass spectrometer. This process also occurs in the 3-nitro analog, where it is dependent on sample residence time in the source and independent of electron energy. It could not be observed with the isomeric 6-substituted tosylates, the 1-substituted acetates or alcohols, or with 2-(p-anisyl)ethyl tosylate. Scrambling occurs in the neutral molecule prior to ionization and a mechanism involving absorption onto the metal surface and formation of a complexed ethylenazulonium ion is suggested.     

N- and C-sulfenylation of 1-(1,2-oxazol-3 (and 5)-yl)-3-alkylureas with organic sulfenyl chlorides

Condensation of chlorocarbonylsulfenyl chloride 1 with 1-(5-(1,1-dimethylethyl)-1,2-oxazol-3-yl)-3-methylurea 4a has been found to give isomeric 2,4-disubstituted-1,2,4-thiazolidine-3,5-diones 5 and 6 . Assignments are confirmed by the X-ray structure data of 6 . Sulfenylation with alkoxycarbonylsulfenyl chlorides 7 and trichloromethylsulfenyl chloride 10 of 4 occurs exclusively on N-1 rather than N-3 of the urea moiety. With the isomeric 1-[3-(1,1-dimethylethyl)-1,2-oxazol-5-yl]-3-methylurea 14 and ethoxycarbonylsulfenyl chloride 7b , C-sulfenylated derivatives 15 and 16 are formed in low yield.     

Six- versus five-membered ring formation in radical cyclizations of 7-bromo-substituted hexahydroindolinones

[reaction: see text] Radical cyclization of N-allyl-7-bromo-3a-methyl-hexahydroindol-2-one affords a six-membered ring product that prevails over the isomeric five-membered compound. The former product is generated through two reaction pathways: (a) 6-endo-trig ring closure and (b) rearrangement of an intermediate methylenecyclopentyl radical obtained by 5-exo-trig cyclization.     

Synthesis and stereochemistry of rac.-trans-tetrahydro-6-hydroxy-7-(4-methoxyphenyl)-1,4-thiazepin-5(2H)-one

The base catalyzed reaction of 2-aminoethanethiol ( 3 ) with trans-3-(p-methoxyphenyl)glycidate ( 4 ) gave a mixture of isomeric lactams 5 and 6 , and in addition, a by-product 7 . The structures of these isomers were proven by X-ray crystallography. The data revealed that both isomers adopt the chair conformation in the solid state and the size of the heterocyclic ring in compound 5 is a six- and in compound 6 is a seven-membered ring.     

3-(4-Thiocarbamoyl-1,2,3-triazol-1-yl)benzo-15-crown-5: synthesis and properties

A reaction of 1,2,3-thiadiazole-4-carbaldehyde with 3-aminobenzo-15-crown-5 involves the Cornforth rearrangement of the 1,2,3-thiadiazole ring, which leads to 1,2,3-triazole-4-carbothioamide containing the benzocrown ether substituent in position 1 of the triazole ring. Reversible formation of the isomeric thiadiazole occurs in aprotic nonpolar solvents such as deuterated chloroform. These compounds are suitable for extraction of α-amino acids from an aqueous phase.     

Dieckmann cyclisation of some β,γ-unsaturated dimethyl esters—I

Dieckmann cyclisation of some β,γ-unsaturated diesters of the indane series gives as major product of the ring closure the compound derived from the more carbanion formed under standardised reaction conditions. The methyl β-(2-methoxycarbonylmethyl-7-methylinden-3-yl)propionate (2) on Dieckmann ring closure, gives 1-methoxycarbonyl-2-oxo-1,2,3,4-tetrahydro-8-methylfluorene (7) and not the isomeric 3-methoxycarbonyl-2-oxo-1,2,3,4-tetrahydro-8-methylfluorene (6) reported earlier.     

Experimental and theoretical studies on carbon-nitrogen clusters C2nN7-

C(2n)N7(-) cluster ions are produced by laser ablating on the K(3)[Fe(CN)6] sample. DFT calculations have been performed for these cluster anions. Various isomeric structures of these clusters are optimized and their energies are compared to find the most stable isomers. The most stable structure for C8N7(-) is similar to that of adenine by theoretical calculation, which is in agreement with the collision-induced dissociation (CID) experimental results. With the increasing even numbers of C atoms from 8 to 16, the N atoms in the double-ring structure are gradually substituted by C atoms from the six-membered ring to the five-membered ring. All these C(2n)N7(-) (n = 3-9) clusters exhibit planar aromatic characters. The energy difference and incremental binding energy analyses show that C(2n)N7(-) (n = 4-8) clusters are more stable than C6N7(-) and C18N7(-), which are consistent with the observed mass spectrum.     

Intramolecular 2+2 addition of a difluorovinyl ether aldehyde yields [3.2.0] And no [3.1.1] products

Irradiation of the difluorovinyl ether aldehyde 6 yields the tricyclic products 7 and 8 and the bicyclic dioxepene 9. There was no evidence for the formation of the isomeric [3.1.1] structure 1 containing the ring system of thromboxane A₂.