Synthesis and stereochemistry of stereoisomeric 1,3-benzoxazino-1,3- and -3,1-benzoxazines

Partly saturated 3,1-benzoxazino[1,2-c][1,3]benzoxazines and 1,3-benzoxazino[3,2-c][1,3]benzoxazines were prepared in one-pot syntheses from different cyclic 1,3-aminoalcohols by treatment with salicylaldehyde or 5-bromosalicylaldehyde, followed by formaldehyde. The structures of tetracycles 3a and 5 were determined by means of X-ray diffraction.     

Synthesis of new fluorinated 1,5-benzoxazepine derivatives

A simple approach to the fluorinated 1,5-benzoxazepine ring system is described. By reacting commercially accessible aminophenols 1 and the trifluoroacetylvinyl ether 2, high yields of enaminones 3 were obtained. Functionalization of methyl group of compounds 3 gave rise to dieneamines 4 that were cyclized in acidic environment to benzoxazepine derivatives 5.     

The Reaction of 2-Aminoethyl- and 3-Aminopropyl-substituted Heterocycles with 2-Formyl-1,3-cyclanediones and 4-Oxo-3,1-benzoxazines

The reaction of 2-formyl-1,3-cyclohexanedione, its 5,5-dimethyl, 5-phenyl and 5-(2-furyl) derivatives and of 2-formyl-1,3-indanedione and dehydroacetic acid with histamine, 3-(1-imidazolyl)propylamine, 3-(4-morpholyl)propylamine, 3-(2-pyrrolidon-1-yl)propylamine, 2-(1-piperazinyl)ethylamine, tryptamine, and 2-(aminomethyl)pyridine gave fifteen 2-aminomethylene derivatives. The reaction of these amines with 2-methyl-4-oxo-3,1-benzoxazine gave the 3-substituted 2-methyl-4(3H)-quinazolinones and with 4-oxo-2-phenyl-3,1-benzoxazine the monosubstituted N-benzoylanthranilic acid amides.     

Stereochemical studies 83 saturated heterocycles 76 : Preparation and conformational study of partially saturated 3,1-benzoxazines, 3,1-benzoxazin-2-ones and 3,1-benzoxazine-2-thiones

The $\text{cis}$- and $\text{trans}$-2-amino-4-cyclohexene-1-carboxylic acids $\text{1}$ and $\text{3}$ react with imidates to give the condensed-skeleton, bicyclic $\text{cis}$- and $\text{trans}$-pyrimidin-4-ones $\text{8}$ and $\text{9}$. The amino acids $\text{1}$ and $\text{3}$ were reduced to the $\text{cis}$-and $\text{trans}$-1, 3-aminoalcohoIs $\text{6}$ and $\text{7}$, which were cyclized by means of imidates to the bicyclic tetrahydro-4$\text{H}$-3,1-benzoxazines $\text{10}$ and $\text{11}$, or were converted, $\text{via}$ the corresponding carbamates $\text{14}$ and $\text{15}$ into the tetrahydro-4$\text{H}$-3,1-benzoxazin-2(1$\text{H}$)-ones $\text{16}$ and $\text{17}$. The 2-thioxo analogues $\text{18}$ and $\text{19}$ were prepared by cyclization of the dithiocarbamates obtained from the aminoalcohols $\text{6}$ and $\text{7}$ by treatment with carbon disulphide. The $\text{trans}$-aminoalcohol $\text{7}$ and its saturated analogue reacted with $\text{p}$-chlorobenzaldehyde to furnish the hexahydro $\text{13}$ and octahydro-4$\text{H}$-3,1-benzoxazine $\text{13a}$, respectively. ¹H and ¹³C NMR studies showed that, similarly to the earlier-investigated analogues containing oxygen or unsubstituted nitrogen at position 1, the synthesized $\text{cis}$ isomrs $\text{8}$, $\text{10}$, $\text{16}$ and $\text{18}$ occurred as the preferred conformer in the heterocyclic twist inverse form of $\text{N}$-inside type ($\text{quasiaxial}$ C₆-N bond) (B). In the $\text{trans}$ isomers containing a saturated C-2 atom ($\text{13}$ and $\text{13a}$), H-2 and H-6 are in $\text{cis}$ relative positions.     

Stereochemical studies. 81. Saturated heterocycles. 69 . Preparation of methylene-bridged 3,1-benzoxazines, 3,1-benzoxazin-2-ones and 3,1-benzoxazine-2-thiones

3-exo-Aminobicyclo[2.2.1]hept-5-ene-2-exo-carboxylic acid and ethyl 3-endo-aminobicyclo[2.2.1]heptane-2-endo-carboxylate ( 6 ) were reduced with lithium aluminum hydride to the corresponding bicyclic aminoalcohols 3 and 4 . These and the saturated endo-endo and exo-exo N-methylaminoalcohols 16 and 22 , respectively, were converted to methylene-bridged tetrahydro- ( 11 ) and hexahydro-3,1-benzoxazin-2-ones 12, 17, 23 and 3,1-benzoxazin-2-thiones 13, 14, 18, 24 . The exo-exo 3 and endo-endo 4 aminoalcohols were cyclized by means of ethyl arylimidates to tricyclic dihydro-1,3-oxazines 7a-d, 8a-d . The structures were confirmed by ir, ¹H and ¹³C nmr spectroscopy.     

Synthesis of novel 1,3,4-benzotriazepine derivatives from 4-oxo-3,1-benzoxazine and 3,1-benzothiazine-2-carbonitriles

Synthesis of novel oxygen and sulfur containing 1,3,4-benzotriazepine derivatives was performed via 3,1-benzoxazine and 3,1-benzothiazine intermediates obtained from Appel's salt chemistry. We observed that the sulfur containing precursors reacted differently than their oxygenated congeners and, after rearrangement, afforded novel heterocyclic compounds (e.g., benzoxazin-4-thione and 2-cyano-1,3,4-triazepine).     

On 1,3-phosphaazaallenes and their diverse reactivity

1,3-Phosphaazaallenes are heteroallenes of the type RP C NR′ and little is known about their reactivity. In here we describe the straightforward synthesis of ArPCNR (Ar = Mes*, 2,4,6-tBu-C₆H₂; ^MesTer, 2.6-(2,4,6-Me₃C₆H₂)–C₆H₃; ^DipTer, 2.6-(2,6-iPr₂C₆H₂)–C₆H₃; R = tBu; Xyl, 2,6-Me₂C₆H₃) starting from phospha-Wittig reagents ArPPMe₃ and isonitriles CNR. It is further shown that ArPCNtBu are thermally labile with respect to the loss of iso-butene and it is shown that the cyanophosphines ArP(H)CN are synthetically feasible and form the corresponding phosphanitrilium borates with B(C₆F₅)₃, whereas deprotonation of ^DipTerP(H)CN was shown to give an isolable cyanidophosphide. Lastly, the reactivity of ArPCNR towards Pier''s borane was investigated, showing hydroboration of the C N bond in Mes*PCNtBu to give a hetero-butadiene, while with ^DipTerPCNXyl the formation of the Lewis acid–base adduct with a B–P linkage was observed.

The combination of phospha-Wittig reagents with isonitriles affords 1,3-phosphaazaallenes and their diverse reactivity has been studied in detail.     

On the preparation of 2-halo alkyl substituted 1,3-dioxolanes and 1,3-dioxanes

Several methods for the preparation of 2-perfluoromethyl-substituted 1,3-dioxolanes and 1,3-dioxanes were tried. The method of Nerdel for the preparation of 1,3-dioxolanes, making use of the condensation between carbonyl compounds and oxiranes, was found to be suitable for perhalogenated ketones and aldehydes, and may even be extended to oxetanes, affording 2-perhaloalkylated 1,3-dioxanes.The yield of the cyclic acetals drops with inreasing substitution.     

Research on 4H-3,1-benzoxazines. 8. Synthesis and properties of 4H-3,1-benzoxazinium chlorides

A mechanism for the acylation of substituted o-aminophenylcarbinols with carboxylic acid chlorides and the formation of 2-alkyl(aryl, furyl)-4H-3,1-benzoxaziniun chlorides is proposed. The nitration and introduction of a sulfur atom into the heterocyclic ring of the 4H-3,1-benzoxazinium salts were investigated.For communication 7 see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 537–541, April, 1993.     

Novel heterocycles. 13 Synthesis of 5,6-dihydro-1H-3H-pyrrolo[3,2,1-ij][3,1]benzoxazine-1,3-dione

The synthesis of 5,6-dihydro-1H,3H-pyrrolo[3,2,1-ij][3,1]benzoxazine-1,3-dione ( 2a ), a new ring system, from N-acetylindoline is described.     

Synthesis and reactions of 4H-3,1-benzothiazines

This study is directed towards the synthesis of the pyrrolo[1,2-α]indole skeleton which is the essential ring system of the active antitumor miomycins. To this end a number of fused heterocycles such as benzothiazines, benzoxazines, indoles and quinolines were synthesized. The structures of the new compounds were assigned by ir, ¹H nmr and ms-data.     

3,1-苯并噁嗪化合物的合成及晶体结构

报道了一种用5-硝基-2-胺基苯甲腈为原料, 在二氯化锌催化下与环酮反应环化合成3,1-苯并噁嗪类化合物的新方法, 并用此方法合成了6-硝基-1,2-二氢-2,2-(1,5-亚戊基)-4-亚胺-4H-3,1-苯并噁嗪(4a). 产物经元素分析、红外光谱、核磁共振氢谱和碳谱进行了表征, 用X射线单晶衍射法测定了其晶体结构. 晶体属单斜晶系, P2₁/c空间群, a＝0.66339(13) nm, b＝2.5329(5) nm, c＝0.73756(15) nm, β＝91.85(3)°, V＝1.2387(4) nm³, Z＝4, D_c＝1.401 g/cm³, F(000)＝552, µ＝0.102 mm^－1, R＝0.0994, wR＝0.3001.     

Studies of 4H-3,1-benzoxazines

Bromination of 2,4-substituted 1,2-dihydro-4H-benzoxazines with bromine in acetic acid was conducted. It was shown that either the corresponding 6,8-dibromo-1,2-hydrobenzoxazines or the products of their dehydrogenation — 6,8-dibromobenzoxazines, are primarily formed as a function of the structure of the dihydrobenzoxazine and the concentration of bromine in the reaction mixture. The structure of 6,8-dibromo-2-(5-nitrofuryl-2)-4, 4-diphenyl-1,2-dihydro-4H-3,1-benzoxazine was investigated by XSA. A stacking interaction between the nitrofuran fragment of one molecule and the condensed benzene ring of the other was detected in the crystal.See [1] for Communication 12.Kuban State Technological University, Krasnodar 350072. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1391–1397, October, 1997.     

New synthesis of nitro-substituted 3,1-benzoxazines

A new one-step procedure has been proposed for the synthesis of nitro derivatives of 3,1-benzoxazines from substituted N-[2-(cyclopent-2-en-1-yl)phenyl]acetamides.     

On the Synthesis and Basicity of 1,3-Diaminoisoquinolines

Summary.  A series of 6- and 7-substituted derivatives of 1,3-diaminoisoquinoline were synthesized by the reaction of N,N-diethylarylacetamides with POCl₃ and then with N,N-dimethylcyanamide. The products were identified by means of spectroscopic methods and their pK _a dissociation constants were determined. Corresponding author. E-mail: kudelkoa@zeus.polsl.gliwice.pl Received July 7, 2002; accepted July 22, 2002