Lewis-acid-catalyzed rearrangement of arylvinylidenecyclopropanes: significant influence of substituents and electronic nature of aryl groups

Lewis-acid-catalyzed reactions of arylvinylidenecyclopropanes having three substituents at the corresponding cyclopropyl rings have been investigated thoroughly. The reaction products are highly dependent on the substituents at the corresponding cyclopropyl rings and the electronic nature of the aryl groups. For arylvinylidenecyclopropanes bearing two alkyl groups at the C-1 position (R1, R2, R3=aryl; R4=H; R5, R6=alkyl), naphthalene derivatives were formed in the presence of Lewis-acid Eu(OTf)3 in DCE at 40 degrees C. For arylvinylidenecyclopropanes in which R1, R2, R3=aryl and R4, R5=alkyl (syn/anti isomeric mixtures), the corresponding 6aH-benzo[c]fluorine derivatives were formed in the syn-configuration via a double intramolecular Friedel-Crafts reaction when all of the aryl groups do not have electron-withdrawing groups or the corresponding indene derivatives were obtained via an intramolecular Friedel-Crafts reaction as long as one electron-deficient aryl group was attached. For arylvinylidenecyclopropanes in which R1, R2, R3, R4=aryl and R5=alkyl or H, the corresponding indene derivatives were obtained exclusively via a sterically demanding intramolecular Friedel-Crafts reaction. Lewis-acid effects and mechanistic insights have been discussed on the basis of experimental investigations.     

Synthesis of trichloromethylpyrimidines and trichloromethylpyrimido [4,5-<Emphasis Type="Italic">d</Emphasis>]pyrimidines from alkyl 2-(diaminomethylidene)-3-oxobutyrates and trichloroacetonitrile

Heterocyclization of alkyl 2-(diaminomethylidene)-3-oxobutyrates with trichloroacetonitrile yields alkyl 4-mino-6-methyl-2-trichloromethylpyrimidine-5-carboxylates. The latter compounds react with aryl isocyanates to produce the corresponding pyrimidinylureas, which undergo cyclization to 3-aryl-5-methyl-7-trichloromethylpyrimido[4,5- d]pyrimidine-2,4(1H,3H)-diones under the action of MeONa in MeOH.     

3-芳胺甲烯基-6-烷基(芳基)-5,6-二氢-2H-吡喃-2,4-二酮的合成及其杀菌活性的研究

以5,6-二氢-6-烷基(芳基)-2H-吡喃-2,4-二酮(1)、芳胺(2)和原甲酸三乙酯进行缩合反应,合成了20个3-芳胺甲烯基-6-烷基(芳基)-5,6-二氢-2H-吡喃-2,4-二酮(3).由于分子内氢键的形成,化合物3由一对构象异构体4和5组成.生物活性初步测定结果表明,这些化合物均有一定的杀菌活性.     

Dihydrocytosines and cytokines from 3-aminopropionitriles

The synthesis of dihydrocytosines 4 from 3-aminopropionitriles 1 has been broadened and the dihydrocytosines themselves have now been successfully converted to cytosines 9 . Unsubstituted 3-(H, alkyl or aryl) aminopropionitriles ( 1 , X = H) convert with cyanate to 1-(H, alkyl or aryl)-1-(2-cyanoethyl)ureas ( 2 , X = H), which in turn easily cyclize with anhydrous strong acid or base to 1-(H, alkyl or aryl)-5,6-dihydrocytosines ( 4 , X = H). The 1-arylaminopropionitriles ( 1 , X = H) which are poorly reactive with cyanic acid combine readily with benzoylureas to form 3-benzoyl-1-(2-cyanoethyl)-1-arylureas ( 3 , X = H). These benzoylureas likewise cyclize with strong acid or base but with simultaneous elimination of the benzoyl moiety to yield the 1-aryldihydrocytosines 4 (X = H). Amines have successfully been added to 2-chloroacrylonitrile to yield 2-chloro-3-(amino and substituted amino)propionitriles ( 1 , X = Cl). These 2-chloropropionitriles also could be converted with cyanate or benzoylisocyanate to ureas and benzoylureas, respectively (1-(H or alkyl)-1-(2-chloro-2-cyanoethyl)ureas ( 2 , X = Cl) or 1-(H or alkyl)-1-(2-chloro-2-cyanoethyl)-3-benzoylureas ( 3 , X = Cl). The chlorine substituted ureas were unstable especially to base and to heat but with anhydrous acid were cyclized in high yield to 1-(H or alkyl)-5-chloro-5,6-dihydro-cytosines ( 4 , X = Cl). Direct chlorination of unsubstituted dihydrocytosines 4 (X = H) did not afford these same 5-chlorodihydrocytosines 4 (X = Cl) under any conditions investigated. 1-Ethyl-5,6-dihydrocytosine ( 4b ) as the cation (hydrobromide) is converted directly in good yield to 1-ethylcytosine hydrobromide ( 7 ) by bromine in nitrobenzene at 140-160° in a concomitant bromination dehydrobromination reaction. 1-(Alkyl or aryl)-5,6-dihydrocytosines ( 4 , X = H) are halogenated at low temperature in the presence of base to form (N³ or N⁴)halogenodihydrocytosines ( 8 , R = H). The N-chlorodihydrocytosines 8 are stable. The N-bromo and N-iodo compounds isomerize spontaneously to 5-halogeno-5,6-dihydrocytosines ( 4 , X = Br, I; R = H). The 5-halogeno-5,6-dihydrocytosines 4 (X = Cl, Br, I) whether from cyclization or direct halogenation are readily dehydrohalogenated to the corresponding cytosines 9.     

Synthesis of 2,3‐dihydro‐1,3‐thiazin‐4(1H)‐ ones and their remarkably facile recyclization to 2,3‐dihydropyrimidin‐4(1H)‐ones

Functionalized 2,3‐dihydro‐1,3‐thiazin‐4(1H)‐one derivatives have been synthesized by cyclocondensation of 3‐alkyl(aryl)amino‐2‐cyano‐3‐mercaptoacrylamides with aldehydes and ketones under acidic catalysis. 6‐Alkyl(aryl)amino‐5‐cyano‐2,3‐dihy‐ dro‐1,3‐thiazin‐4(1H)‐ones, when treated with a dilute solution of potassium hydroxide, are converted into the potassium salts of isomeric compounds, 1‐alkyl‐ (aryl)‐5‐cyano‐6‐mercapto‐2,3‐dihydropyrimidin‐ 4(1H)‐ones. Alkylation of the latter with dimethyl sulfate in situ furnishes 1‐alkyl(aryl)‐6‐alkylthio‐5‐ cyano‐2,3‐dihydropyrimidin‐4(1H)‐ones, whereas boiling them in ethanol with an excess of hydrochloric acid leads to starting 2,3‐dihydro‐1,3‐thiazin‐4(1H)‐ones. © 2005 Wiley Periodicals, Inc. Heteroatom Chem 16:426–436, 2005; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20129     

Dissociative electron attachment to triflates

Gas phase studies of dissociative electron attachment to simple alkyl (CF(3)SO(3)CH(3)) and aryl (C(6)H(5)SO(3)CF(3) and CF(3)SO(3)C(6)H(4)CH(3)) triflates, model molecules of nonionic photoacid generators for modern lithographic applications, were performed. The fragmentation pathways under electron impact below 10 eV were identified by means of crossed electron-molecular beam mass spectrometry. Major dissociation channels involved C-O, S-O, or C-S bond scissions in the triflate moiety leading to the formation of triflate (OTf(-)), triflyl (Tf(-)), or sulfonate (RSO(3)(-)) anions, respectively. A resonance leading to C-O bond breakage and OTf(-) formation in alkyl triflates occurred at electron energies about 0.5 eV lower than the corresponding resonance in aryl triflates. A resonance leading to S-O bond breakage and Tf(-) formation in aryl triflates occurred surprisingly at the same electron energies as C-O bond breakage. In case of alkyl triflates S-O bond breakage required 1.4 eV higher electron energies to occur and proceeded with substantially lower yields than in aryl triflates. C-S bond scission occurred for all presently studied triflates at energies close to 3 eV.     

An efficient and regioselective synthesis of 1,1′-oxalylbis[3-(alkyl/aryl/heteroaryl)-5-(trihalomethyl)-1H-pyrazoles] from 4-alkoxy-1,1,1-trihaloalk-3-en-2-ones

Abstract  

This work describes the regioselective synthesis of two new series of 1,1′-oxalylbis[3-(alkyl/aryl/heteroaryl)-4,5-dihydro-5-hydroxy-5-(trihalomethyl)-1H-pyrazoles], where the 3-substituents are H, Me, C₆H₅, 4-FC₆H₄, 4-ClC₆H₄, 4-BrC₆H₄, 4-NO₂C₆H₄, 4,4′-BiPh, and 2-furyl, in a one-pot methodology with ethanol as solvent, from the reaction of 4-alkoxy-4-(alkyl/aryl/heteroaryl)-1,1,1-trihaloalk-3-en-2-ones with oxalyldihydrazide (51–89%). Complementarily, the dehydration reactions of five examples of the described oxalylbispyrazolines are also reported, which furnished the respective 1,1′-oxalylbis[3-(alkyl/aryl/heteroaryl)-5-(trihalomethyl)-1H-pyrazoles] in 53–78% yields without the two C(O)–N bond cleavages.     

New Approaches to the Synthesis of 4‐(2‐Aminophenyl)‐1,3‐dihydro‐2H‐imidazol‐2‐ones and 3‐Ureidoindoles and a Study of Their Interconversion

3‐Alkyl/aryl‐3‐ureido‐1H,3H‐quinoline‐2,4‐diones ( 2 ) and 3a‐alkyl/aryl‐9b‐hydroxy‐3,3a,5,9b‐tetrahydro‐1H‐imidazo[4,5‐c]quinoline‐2,4‐diones ( 3 ) react in boiling concentrated HCl to give 5‐alkyl/aryl‐4‐(2‐aminophenyl)‐1,3‐dihydro‐2H‐imidazol‐2‐ones ( 6 ). The same compounds were prepared by the same procedure from 2‐alkyl/aryl‐3‐ureido‐1H‐indoles ( 4 ), which were obtained from the reaction of 3‐alkyl/aryl‐3‐aminoquinoline‐2,4(1H,3H)‐diones ( 1 ) with 1,3‐diphenylurea or by the transformation of 3a‐alkyl/aryl‐9b‐hydroxy‐3,3a,5,9b‐tetrahydro‐1H‐imidazo[4,5‐c]quinoline‐2,4‐diones ( 3 ) and 5‐alkyl/aryl‐4‐(2‐aminophenyl)‐1,3‐dihydro‐2H‐imidazol‐2‐ones ( 6 ) in boiling AcOH. The latter were converted into 1,3‐bis[2‐(2‐oxo‐2,3‐dihydro‐1H‐imidazol‐4‐yl)phenyl]ureas ( 5 ) by treatment with triphosgene. All compounds were characterized by ¹H‐ and ¹³C‐NMR and IR spectroscopy, as well as atmospheric pressure chemical‐ionisation mass spectra.     

A detailed study of the intramolecular hydroamination of N-(ortho-alkynyl)aryl-N'-substituted trifluoroacetamidines and bromodifluoroacetamidines

The intramolecular hydroamination of N-(ortho-alkynyl)aryl-N'-substituted trifluoroacetamidines and bromodifluoroacetamidines is studied in detail. When the substituents on the alkyne fragment are aryl and alkyl groups, 5-endo-dig cyclization occurs utilizing NaAuCl(4)·2H(2)O as a catalyst, while 6-exo-dig cyclization proceeds in the presence of K(2)CO(3) as a base. Interestingly, the indole derivatives are afforded with good regioselectivity via a 5-endo-dig pathway catalyzed by Cu(OAc)(2) when ortho-ethynyl appears on the aryl substituent of the amidine. The electrophilic cyclization of the amidines also shows good regioselectivity under the I(2)/NaHCO(3) system. At the end, a facile cascade synthesis of fluorinated quinazolones is described via hydroamination/ozonolysis from the corresponding amidine.     

C(arenium)-C(alkyl) bond making and breaking: key process in the platinum-mediated C(aryl)-C(alkyl) bond formation. Analogies to organic electrophilic aromatic substitution

The reaction of cationic platinum aqua complexes 2 [Pt(C(6)H(2)[CH(2)NMe(2)](2)-E-4)(OH(2))](X') (X' = SO(3)CF(3), BF(4)) with alkyl halides RX gave various air-stable arenium complexes 3-5 containing a new C-C bond (R = Me, 3; Et, 4; Bn, 5). Electron-releasing oxo-substituents on the aromatic ligand (E = e.g., OH, b; OMe, c) enhance the reactivity of the aqua complex 2 and were essential for arenium formation from alkyl halides different from MeX. This process is initiated by oxidative addition of alkyl halides to the platinum(II) center of 2, which affords (alkyl)(aryl) platinum(IV) complexes (e.g., 9, alkyl = benzyl) as intermediates. Spectroscopic analyses provided direct evidence for a subsequent reversible 1,2-sigmatropic shift of the alkyl group along the Pt-C(aryl) bond, which is identical to repetitive C(arenium)-C(alkyl) bond making and breaking and concerted metal reduction and oxidation. Temperature-dependent NMR spectroscopy revealed DeltaH degrees = -1.3 (+/- 0.1) kJ mol(-1), DeltaS degrees = +3.8 (+/- 0.2) J mol(-1) K(-1), and DeltaG degrees (298) = -2.4 (+/- 0.1) kJ mol(-1) for the formation of the arenium complex 5b from 9 involving the migration of a benzyl group. The arenium complexes were transformed to cyclohexadiene-type addition products 7 or to demetalated alkyl-substituted arenes, 8, thus completing the platinum-mediated formation of a sp(2)-sp(3) C-C bond which is analogous to the aromatic substitution of a [PtX](+) unit by an alkyl cation R(+). The formation of related trimethylsilyl arenium complexes 6 suggests arenium complexes as key intermediates, not only in (metal-mediated) sp(2)-sp(3) C-C bond making and breaking but also in silyl-directed cyclometalation.     

Innovative synthesis of 4-carbaldehydepyrrolin-2-ones by zwitterionic rhodium catalyzed chemo- and regioselective tandem cyclohydrocarbonylation/CO insertion of alpha-imino alkynes

The tandem cyclohydrocarbonylative/CO insertion of alpha-imino alkynes employs CO, H(2), and catalytic quantities of zwitterionic rhodium complex (eta(6)-C(6)H(5)BPh(3))(-)Rh(+)(1,5-COD) and triphenyl phosphite affording aldehyde substituted pyrrolinones in 67-82% yields. This unique transformation is readily applied to imino alkynes containing alkyl, alkoxyl, vinyl, and aryl substituents. The ability to prepare highly functionalized pyrrolinones makes this an attractive route to these important and versatile pharmaceuticals.     

Synthesis of derivatives of 4-alkylthiouracil,cytosine, pyrido[2,3-d]pyrimidine,and pyrimido[4,5-d]pyrimidine from the N,S- and N,N-acetals of diacetylketene and isocyanates

The action of alkyl and aryl isocyanates on the N,S-acetals of diacetylketene leads to the formation of 4-alkylthio-5-acetyl-1-alkyl(aryl)-6-methyl-1H-pyrimidin-2-ones (derivatives of 4-alkylthiouracils). The reaction of the synthesized thiouracils with amines or the reaction of the N,N-acetals of diacetylketene (N,N-ADK) with an equi-molar amount of aryl isocyanates leads to the formation of substituted 4-amino-5-acetyl-1H-pyrimidin-2-ones (derivatives of cytosine). From the latter and isocyanates or directly from N,N-ADK and an excess of the isocyanate, derivatives of 4-methylene-1H,3H, 4H-pyrimido[4,5-d]pyrimidine-2,7-dione were obtained. The exception was the condensation of 3-[N-(4,6-dimethyl-2-pyrimidinyl)diaminomethylene]pentane-2,4-dione with aryl isocyanates, which led to 3H,8H-pyrido[2,3-d]pyrimidine-2,5-diones.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 11, pp. 2593–2599, November, 1991.     

NMR spectral study of some 2r,6c-diarylpiperidin-4-one (3'-hydroxy-2'-naphthoyl)hydrazones with special reference to γ-syn effect

1H and 13C NMR spectra have been recorded for 2r,6c-diarylpiperidin-4-one (3'-hydroxy-2'-naphthoyl)hydrazones 10-17 and 3,3-dimethyl-2r,6c-bis(p-methoxyphenyl)piperidin-4-one (5). For selected compounds 2D NMR spectra have been recorded. The spectral data along with those reported for related compounds are used to study the effect of a heteroatom X on the 13C chemical shift of a γ-carbon with X Cα Cβ Cγ torsional angle close to 0°, termed as γ-syn effect. Also γ-gauche and δ-effects of the alkyl groups at C-3 on the carbons of the aryl group at C-2 have been studied. The chemical shifts for the naphthalene ring are in accord with the mesomeric and steric effects of the carbonyl and hydroxy groups.     

Synthesis of novel 5-chloro-2-(thiophen-2-yl)-7,8-dihydroquinoline-6-carboxamides as potent inhibitors of Mycobacterium tuberculosis

A series of novel 5-chloro-2-(thiophen-2-yl)-7,8-dihydroquinoline-6-carboxamides was designed, synthesized, and evaluated for antitubercular activity. The required 5-chloro-2-(thiophen-2-yl)-7,8-dihydroquinoline-6-carboxylic acid intermediate was prepared by oxidizing the respective aldehyde with sodium chlorite and 30% H2O2. Further, the acid was coupled with various aryl, alkyl, and heterocyclic amines using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride and hydroxybenzotriazole to give the desired 5-chloro-2-(thiophen-2-yl)-7,8-dihydroquinoline-6-carboxamides in excellent yields. All the new compounds were characterized by their NMR and mass spectral analysis. Screening of all new compounds for in vitro antimycobacterial activity against M. tuberculosis H37Rv (Mtb) resulted in five analogs with MIC 3.12 µg/cm3 as promising antitubercular agents with lower cytotoxicity profiles.     

A mechanistic investigation of the carbon-carbon bond cleavage of aryl and alkyl cyanides using a cationic RhIII silyl complex

Cationic Rh(III) complex [Cp(PMe(3))Rh(SiPh(3))(CH(2)Cl(2))]BAr(4)' (1) activates the carbon-carbon bond of aryl and alkyl cyanides (R-CN, where R = Ph, (4-(CF(3))C(6)H(4)), (4-(OMe)C(6)H(4)), Me, (i)Pr, (t)Bu) to produce complexes of the general formula [Cp*(PMe(3))Rh(R)(CNSiPh(3))]BAr(4)'. With the exception of the (t)BuCN case, every reaction proceeds at room temperature (t(1/2) < 1 h for aryl cyanides, t(1/2) < 14 h for alkyl cyanides). A general mechanism is presented on the basis of (1) an X-ray crystal structure determination of an intermediate isolated from the reaction involving 4-methoxybenzonitrile and (2) kinetic studies performed on the C-C bond cleavage of para-substituted aryl cyanides. Initial formation of an eta(1)-nitrile species is observed, followed by conversion to an eta(2)-iminoacyl intermediate, which was observed to undergo migration of R (aryl or alkyl) to rhodium to form the product [Cp*(PMe(3))Rh(R)(CNSiPh(3))]BAr(4)'.     

Pyridine N-alkylation by lithium, magnesium, and zinc alkyl reagents: synthetic, structural, and mechanistic studies on the bis(imino)pyridine system

The 2,6-bis(alpha-iminoalkyl)pyridines 2,6-[ArNC(CR(3))](2)C(5)H(3)N [R = H, D; Ar = 2,6-i-Pr(2)C(6)H(3) (DIPP), 2,6-Me(2)C(6)H(3) (DMP)] react with MeLi in Et(2)O to give a binary mixture of products: the pyridine N-methylated species 2,6-[ArNC(CR(3))](2)C(5)H(3)N(Me)Li(OEt(2)) and the deprotonated/dedeuterated species 2-[ArNC(CR(3))],6-[ArNC(=CR(2))]C(5)H(3)NLi(OEt(2)). For R = D, the product ratio is 2:1 in favor of the N-methylated product, while, for R = H, the deprotonated product is favored by 5:1, increasing to 8:1 in toluene solvent. Warming solutions of the N-methylated species leads to clean conversion to the thermodynamically preferred deprotonated species. Crossover experiments show that MeLi is re-formed and dissociates from the terdentate ligand before deprotonating the ketimine methyl unit. For MgR(2) (R = Et, i-Pr) and ZnR(2) (R = Et) reagents, N-alkylation products are formed exclusively, but derivatives containing bulky aryl substituents are found to undergo further rearrangement to 2-alkylated species, arising by migration of the alkyl group of the N-alkyl moiety to the adjacent ring carbon atom. The reversibility of the N-alkylation process has been probed using deuterio-labeled Mg alkyl reagents and mixed alkyl zinc species. A cationic zinc derivative is shown to undergo "reverse" alkyl migration, from the heterocycle nitrogen atom to the zinc center. EPR spectroscopy reveals a paramagnetic intermediate in which the unpaired electron is delocalized over the heterocycle and di-imine moieties of the ligand, indicating that the N-alkylation reactions proceed via single electron-transfer processes.     

C-H activation motivated by N,N'-diisopropylcarbodiimide within a lutetium complex stabilized by an amino-phosphine ligand

A lutetium bis(alkyl) complex stabilized by a flexible amino-phosphine ligand LLu(CH(2)Si(CH(3))(3))(2)(THF) (L = (2,6-C(6)H(3)(CH(3))(2))NCH(C(6)H(5))CH(2)P(C(6)H(5))(2)) was prepared which upon insertion of N,N'-diisopropylcarbodiimide led to C-H activation via metalation of the ligand aryl methyl followed by reduction of the C[double bond, length as m-dash]N double bond.     

3-(2'-苯基-1', 2', 3'-连三唑-4'-基)-6-烷基/芳基-均三唑并[3, 4-b]-1, 3, 4-噻二唑的合成

研究了3-(2'-苯基-1', 2', 3'-连三唑-4'-基)-4-氨基-5-巯基-1, 2, 4-三唑(1)与取代苯甲酸和脂肪酸(2a-r)在POCl3催化下的反应, 共合成得到18个新的3-(2'-苯基-1', 2', 3'-连三唑-4'-基)-6-烷基/芳基-均三唑并[3, 4-b]-1, 3, 4-噻二唑(3a-r), 经元素分析,IR, 1H NMR和MS进行了结构确证。     

Catalytic C-H bond amination from high-spin iron imido complexes

Dipyrromethene ligand scaffolds were synthesized bearing large aryl (2,4,6-Ph(3)C(6)H(2), abbreviated Ar) or alkyl ((t)Bu, adamantyl) flanking groups to afford three new disubstituted ligands ((R)L, 1,9-R(2)-5-mesityldipyrromethene, R=aryl, alkyl). While high-spin (S=2), four-coordinate iron complexes of the type ((R)L)FeCl(solv) were obtained with the alkyl-substituted ligand varieties (for R=(t)Bu, Ad and solv=THF, OEt(2)), use of the sterically encumbered aryl-substituted ligand precluded binding of solvent and cleanly afforded a high-spin (S=2), three-coordinate complex of the type ((Ar)L)FeCl. Reaction of ((Ad)L)FeCl(OEt(2)) with alkyl azides resulted in the catalytic amination of C-H bonds or olefin aziridination at room temperature. Using a 5% catalyst loading, 12 turnovers were obtained for the amination of toluene as a substrate, while greater than 85% of alkyl azide was converted to the corresponding aziridine employing styrene as a substrate. A primary kinetic isotope effect of 12.8(5) was obtained for the reaction of ((Ad)L)FeCl(OEt(2)) with adamantyl azide in an equimolar toluene/toluene-d(8) mixture, consistent with the amination proceeding through a hydrogen atom abstraction, radical rebound type mechanism. Reaction of p-(t)BuC(6)H(4)N(3) with ((Ar)L)FeCl permitted isolation of a high-spin (S=2) iron complex featuring a terminal imido ligand, ((Ar)L)FeCl(N(p-(t)BuC(6)H(4))), as determined by (1)H NMR, X-ray crystallography, and (57)Fe Mo?ssbauer spectroscopy. The measured Fe-N(imide) bond distance (1.768(2) ?) is the longest reported for Fe(imido) complexes in any geometry or spin state, and the disruption of the bond metrics within the imido aryl substituent suggests delocalization of a radical throughout the aryl ring. Zero-field (57)Fe Mo?ssbauer parameters obtained for ((Ar)L)FeCl(N(p-(t)BuC(6)H(4))) suggest a Fe(III) formulation and are nearly identical with those observed for a structurally similar, high-spin Fe(III) complex bearing the same dipyrromethene framework. Theoretical analyses of ((Ar)L)FeCl(N(p-(t)BuC(6)H(4))) suggest a formulation for this reactive species to be a high-spin Fe(III) center antiferromagnetically coupled to an imido-based radical (J = -673 cm(-1)). The terminal imido complex was effective for delivering the nitrene moiety to both C-H bond substrates (42% yield) as well as styrene (76% yield). Furthermore, a primary kinetic isotope effect of 24(3) was obtained for the reaction of ((Ar)L)FeCl(N(p-(t)BuC(6)H(4))) with an equimolar toluene/toluene-d(8) mixture, consistent with the values obtained in the catalytic reaction. This commonality suggests the isolated high-spin Fe(III) imido radical is a viable intermediate in the catalytic reaction pathway. Given the breadth of iron imido complexes spanning several oxidation states (Fe(II)-Fe(V)) and several spin states (S=0→(3)/(2)), we propose the unusual electronic structure of the described high-spin iron imido complexes contributes to the observed catalytic reactivity.     

Synthesis of substituted 4-oxo-2-thioxo-1,2,3,4-tetrahydroquinazolines and 4-oxo-3,4-dihydroquinazoline-2-thioles

We have developed a liquid-phase synthesis of combinatorial libraries of new disubstituted 4-oxo-2-thioxo-1,2,3,4-tetrahydroquinazolines and trisubstituted 4-oxo-3,4-dihydroquinazoline-2-thioles. The former were prepared using two general procedures: (i) cyclization of substituted methyl anthranilates with isothiocyanates, or (ii) cyclization of substituted 2-(methylcarboxy)benzeneisothiocyanates with primary amines or hydrazines. 4-Oxo-3,4-dihydroquinazoline-2-thioles were prepared by S-alkylation of disubstituted 4-oxo-2-thioxo-1,2,3,4-tetrahydroquinazolines with alkyl or aryl halides. The hydrolysis of methyl benzimidazo[1,2-c]quinazoline-6(5H)-thione-3-carboxylate led to the corresponding acid. This acid was utilized in the synthesis of new benzimidazo[1,2-c]quinazoline-6(5H)-thione-3-carboxamide and S-substituted 6-mecaptobenzimidazo[1,2-c]quinazoline-3-carboxamide libraries.