Cyclization reaction of N-

Interesting observations were made on the cyclization reactions of N-benzoyl-CM- and fram-2-aminomethyl-l-cyclanols 216 and 217 with P4S10. From the cm isomers the spiro derivatives 219 were the main products, while the cm thiazines 220 were the minor products. In the cyclization of... 

The position of the alkene is crucial for efficient cyclization. Reactions of N-lithio-5-hexenamine led to only a trace of the piperidine from 6-exo cyclization. Reactions of N-lithio-3-butenylamine gave no cyclic products the acyclic amine and products most likely the result of /3-scission were obtained (87T281). 

The methodology was successfully extended to a one-pot total synthesis of complex heterocyclic systems such as pyrazino [2,1-b] quinazolines 79, encountered in nature as alkaloids 80-82 (Scheme 50) [125]. To assemble the pyrazino[2,l-fo]quinazoline core, N-Boc protected amino acid 76 was employed instead of carboxylic acid 72 (Scheme 49) in the synthesis of the corresponding intermediate benzoxazinones 77. The subsequent reaction with an amine moiety of another amino acid ester 78 was accompanied by concomitant cleavage of the N-Boc protecting group and diketopiperazine-like cyclization (for the one-pot deprotection-cyclization reaction of N-Boc dipeptide esters to afford 2,5-piperazinedione under microwave dielectric heating, see [128]) to afford the target heterocycle 79. Hence, the total... 

The first building block, the commercially available 11, is synthesized by a base-catalyzed cyclization reaction of N-cyano-dimethyldithioimidocarbonate (10a, CIDT) [65, 66] or N-cyano-dimethyl-imidocarbonate (10b, DCC) [67] with cyste-amine hydrochloride. From the technical process for 1, several attractive synthetic routes are described for the preparation of 5 (Table 29.2.2.3). Finally, the technical process is readily available by N-alkylation of 11 with 5. 

A chiral menthol auxiliary has been utilized by Hoffmann and coworkers for the radical addition/cyclization reaction of N,N-dimethylaniline 242 with 5R)-menthyloxyfuran-2(5H)-one 245 using photochemical electron transfer (PET). The reaction led to 246 and 247 with 44% yield and 3.3 1 diastereoselectivity [77, 78] (Scheme 5.52). A modified menthol auxiliary was utilized for the asymmetric synthesis of a chiral precursor to the natural terpenoid (+)-triptocallol by Yang and coworkers [79]. The reaction was performed under oxidative radical conditions mediated by l.Oequiv of Yb(OTf)3 and 2.2equiv of Mn(0Ac)3-2H20 Mn(OAc)3. Reasonable yields of 55-72% and a diastereoselectivity of 24.2 1-2.8 1 were... 

Shin, C., K. Nanjo, and J. Yoshimura Cyclization Reaction of N-(Haloacyl)- or N-(Phthaloylglycyl)-hydroxyamino Acid Esters with Ammonia. Chem. Letters (Japan) 1973, 1039. 

The polymerization of o,o-dlacetylenediphenyl glutarate and 5,7-dodecadiinediol-l,12 bis-phenylurethane. (b) The cyclization reaction of N-(para-chlorophenyl) phthalanilic acid to N-(para-chlorophenyl) phthalimidle with the elimination of water. (c) The polymerization of crystalline methacrylic acid. Finally a discussion will be undertaken of the polymerization of molecular multilayers of a number of monomers, such as vinyl stearates and a-octadecylacrylic acid, which may not fit conveniently into any of the above categories. 

THE CYCLIZATION REACTION OF N-(p-CHLOROPHENYL) PHTHALANILIC ACID TO N-(p-CHLOROPHENYL) PHTHALIMIDE... 

Ma H, Li D, Yu W (2016) Synthesis of quinoxaline derivatives via tandem oxidative azidation/cyclization reaction of N-arylenamines. Org Lett 18(4) 868-871... 

Pattenden and coworkers investigated radical cyclization reactions of N-propargyl bromoacetamides mediated by tributyltin hydride in some... 

Dimethyl acetylenedicarboxylate (80) undergoes initial 1,2 cycloaddition with acyclic enamines to form cyclobutene intermediates which immediately decompose into acyclic dienaminodiesters (94,95). When an acyclic n/c-enediamine is used instead of a simple acyclic enamine, a dienediamino-diester is produced via a cyclobutene intermediate (95a). A cyclization reaction of dimethyl acetylenedicarboxylate with an acyclic enaminoketone... 

The reaction of N-amino heterocycles 759 and 760 with diaryl carbodii-mide gave triazolotriazine 761 in good yield. In some cases the intermediate guanidines are isolated which by thermal or basic treatment cyclized (86H3363 89H1607) to neutral or mesoionic compounds. 

Although efficient for the intramolecular hydroamination/cyclization (abbreviated IH below) of aminoalkenes (see below), organolanthanides exhibit a much lower catalytic activity for the intermolecular hydroamination of aUcenes, as exemplified by the reaction of n-PrNH2 with 1-pentene catalyzed by a neodymium complex (Eq. 4.17) [127]. 

In a related example, reaction of N-hydroxy-N-methylthiophene-2-carboximidamide 56 with DMAD gave a double Michael addition product 57, which when heated at reflux in xylenes, afforded hydroxypyrimidinone 60 in 57% overall yield (Scheme 6.21) [9f]. The mechanism invoked was opening of the oxa-diazole 57 to 58, followed by a [3,3]-Claisen-type rearrangement to 59, which, after tautomerization and cyclization, afforded 60. 

Hydrazones are also useful substrates in the preparation of pyrazoles. Reaction of N-monosubstituted hydrazones with nitroolefins led to a regioselective synthesis of substituted pyrazoles <060L3505>. lf/-3-Ferrocenyl-l-phenylpyrazole-4-carboxaldehyde was achieved by condensation of acetylferrocene with phenylhydrazine followed by intramolecular cyclization of the hydrazone obtained under Vilsmeier-Haack conditions <06SL2581>. A one-pot synthesis of oxime derivatives of l-phenyl-3-arylpyrazole-4-carboxaldehydes has been accomplished by the Vilsmeier-Haack reaction of acetophenone phenylhydrazones <06SC3479>. 

In a separate study, Ohberg and Westman applied the same PS-DMAP in a one-pot microwave-induced base-catalyzed reaction of N-aryl and N-alkyl amino acids (or esters) and thioisocyanates for the library synthesis of thiohydantoins (Scheme 7.115) [136]. Thiohydantoins are of interest due to their ease of preparation and the range of biological properties associated with this heterocyclic ring system. The use of PS-DMAP as the base in this reaction gave slightly lower yields compared to when triethylamine (TEA) was used, but it resulted in a cleaner reaction mixture and an easier purification procedure. Cyclizations of a number of N-substituted... 

Reaction of 6-halopurines with Michael acceptors under Heck conditions gives N- -substituted hypoxanthine derivatives <00CCC797>. Reactions of a series of 1-aminobenzimidazoles and l-amino-3-methylbenzimidazolium chlorides with 2,4-pentanediones afford pyridazino[l,6-a]benzimidazoles and 2-pyrazolylanilines, the product ratio depending on conditions and on the electronic character of the substituents at the benzene moiety <00BMC37>. Cyclization reactions of adenine derivative 75 with different amines or hydrazine afford tricyclic polyaza compounds 76 <00CCC1109>. 

The synthesis of the corresponding naphthyridone scaffold was carried out according to the methods reported by Chu et al. [12] and Sanchez et al. [13]. Namely, the hydrolysis of ethyl 2,6-dichloro-5-fluoronicotinate (3) [14] followed by reaction with thionyl chloride results in the formation of 2,6-dichloro-5-fluoronicotinyl chloride (4). Treatment of this compound with monoethyl malonate in THF under n-butyllithium followed by acidification and decarboxylation gives rise to ethyl 2,6-dichloro-5-fluoronicotinylacetate (5). Reaction of compound 5 with ethyl orthoformate in acetic acid followed by cyclopropylamine results in the formation of 3-cyclopropylamino-2-(2,6-dichloro-5-fluoronicotinyl)acrylate (6), the cyclization reaction of which under NaH/THF gives rise to the required ethyl l-cyclopropyl-6-fluoro-7-chloro-l,4-dihydro-4-oxo-l,8-naphthyridine-3-carboxylate (7), as shown in Scheme 3. 

Reaction of N-(2-bromoallyl)-N-prop-2-ynylamines 72 with tert-butyllithium, followed by reaction with zirconocene methyl chloride and subsequent cyclization gives 1,1-lithio-zirconioalkenes 73 via 74 and intermediate 75 (Scheme 7.23) [144,145], Treatment of the lithiozirconium complex 73 with deuterated sulfuric acid leads to the trideuterated pyrrolidine 76. 

The electrocyclic reactions of n systems containing an impaired electron are difficult to interpret using the above simple theories. The symmetry of the HOMO of the radical system corresponds to that of the corresponding anion. Thus the allyl radical would be expected to cyclize in the same manner as the alkyl anion i.e., in a conrotatory manner. In fact the interconversion takes place in a disrotatory manner. Theoretical calculations based on Huckets theory also give ambiguous or incorrect predictions. And therefore more sophisticated calculations are required to obtain reliable results. 

Dioxotetrahydropyrimidine-5-carboxylates (1341) were prepared in 50-72% yields, by the cyclization of (V-(aminocarbonyl)aminomethy-lenemalonates (1340) in alcohol by the action of sodium alcoholate, or in 48-97% yields in the reaction of /V-substituted urea and EMME in ethanol in the presence of sodium ethylate at room temperature for several days. Compounds 1341 were also prepared in 41 and 62% yields, respectively, in the reactions of N-methyl- and /V,N -dimethylurea and EMME in the melt at 120°C for 24 hr (52JA4267). 

Azetidones (p-lactams) are generally obtained in high yield from (3-halopropion-amides (Table 5.18) and the low yield from the reaction of N-phenyl (3-chloropropi-onamide can be reconciled with the isolation of A-phenyl acrylamide in 58% yield [34]. The unwanted elimination reaction can be obviated by conducting the cyclization in a soliddiquid system under high dilution [35, 36]. Azetidones are also formed by a predominant intramolecular cyclization of intermolecular dimerization to yield piperazine-2,5-diones, or intramolecular alkylation to yield aziridones. Aone-pot formation of azetidones in 45-58% yield from the amine and P-bromocarboxylic acid chloride has also been reported [38]. 

Aromatization of hydrocarbons with more than six carbon atoms is thermodynamically even more favorable than the reaction of n-hexane 28). These hydrocarbons offer more than one way of cyclization, for example, n-octane may give either o-xylene or ethylbenzene. -Nonane can even give bicyclic products (indane system) (72). 

Sprio et al. reported the preparation of 6-acetylimidazo[2,l-Z)]thiazoles derivatives 57 (74JHC91). TTie synthesis involves substituted 4-(2-thiazo-lyl)aminoisoxazoles 56, which were obtained in good yield by the reaction of N-(3,5-dimethylisoxazol-4-yl) thiourea 55 with a-chloro ketones. Subsequent isoxazole ring opening led to intermediates which readily underwent cyclization by refluxing in acetic acid or ethanol/hydrochloric acid. 

Some A -enecarboxylic acids undergo a rapid intramolecular cyclization reaction of the 5-exo-trig type prior to the radical coupling step. Substituted tetrahydro-furans [95] and pyrrolidines [96] can be prepared by this Kolbe route. It is preferable to protect the amine function in the pyrrolidine synthesis by N-formy ation in... 

Reaction of N-benzoyl isoindolin-l-one with 2-lithio-l-phenylsulfonylindole takes place at both lactam and acyclic carbonyl groups generating a separatable 4 3 mixture of ketone 33 with 2-benzoyl-l-phenylsulfonylindole. When the reaction is allowed to proceed for longer than ca. 15 min, cyclized product 34 is formed as the result of an intramolecular nucleophilic substitution. Compound 34 can be obtained from the isolated ketone 33 in good yield on exposure to NaH in refluxing THE (Scheme 5 (1996TL4283)). 

A. Kittaka, T. Asakura, T. Kuze, H. Tanaka, N. Yamada, K. T. Nakamura, and T. Miyasaka, Cyclization reactions of nucleoside anomeric radical with olefin tethered on base Factors that induce anomeric stereochemistry,/. Org. Chem., 64 (1999) 7081-7093. 

Cyclization by amidomercuration has been reported (391). Reaction of N-methoxycarbonyl-6-aminohept-l-ene (211) with mercuric acetate gave the organomercurial (212). Reductive coupling of 212 with l-decen-3-one in the usual way gave the cis and trans isomers (213). Successive treatment of 213 with ethanedithiol, Raney nickel, and ethanolic hydrogen chloride afforded ( )-sole-nopsin A (Id, 2 parts) and its isomer (Ic, 3 parts), which were separable by preparative gas chromatography (GC) (Scheme 5) (391). 

Based on the previous findings by Koomen [21], the Hiemstra group subsequently reported the Pictet-Spengler reaction of N-tritylsulfenyl tryptamines and various aliphatic and aromatic aldehydes by 11 (Scheme 5.11) [22]. Notably, the authors found that stabilization of the N-sulfenyliminium ion by the sulfenyl substituent facilitated preferential cyclization over enamine formation. 

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