Preparation of 1,3‐diphosphabuta‐1,3‐dienes from sterically encumbered phosphaalkyne and phosphaethenyllithium

Kinetically stabilized 2‐lithio‐1‐(2,4,6‐tri‐t‐butylphenyl)‐1‐phosphapropene was allowed to react with a bulky phosphaalkyne Mes*CP (Mes* = 2,4,6‐t‐Bu₃C₆H₂) followed by quenching with iodomethane or benzyl bromide to give the corresponding 1,3‐diphosphabuta‐1,3‐dienes. The presence of the bulky Mes* group on the 1‐phosphorus atom prevents intramolecular [2+2] cyclization and gave the PC PC skeleton, whereas Mes*CP reacted with half an equivalent of nucleophile to afford the PCPC four‐membered ring compounds. X‐ray crystallography of 4‐benzyl‐1,3‐diphosphabuta‐1,3‐diene confirmed the molecular structure showing conjugation on the 1,3‐diphosphabuta‐1,3‐diene moiety. © 2005 Wiley Periodicals, Inc. Heteroatom Chem 16:357–360, 2005; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20104     

Hydrogen‐bonded ribbons in ethyl (E)‐3‐[2‐amino‐4,6‐bis(dimethylamino)pyrimidin‐5‐yl]‐2‐cyanoacrylate and 2‐[(2‐amino‐4,6‐di‐1‐piperidylpyrimidin‐5‐yl)methylene]malononitrile

The pyrimidine rings in ethyl (E)‐3‐[2‐amino‐4,6‐bis(dimethylamino)pyrimidin‐5‐yl]‐2‐cyanoacrylate, C₁₄H₂₀N₆O₂, (I), and 2‐[(2‐amino‐4,6‐di‐1‐piperidylpyrimidin‐5‐yl)methylene]malononitrile, C₁₈H₂₃N₇, (II), which crystallizes with Z′ = 2 in the space group, are both nonplanar with boat conformations. The molecules of (I) are linked by a combination of N—H...N and N—H...O hydrogen bonds into chains of edge‐fused R₂²(8) and R₄⁴(20) rings, while the two independent molecules in (II) are linked by four N—H...N hydrogen bonds into chains of edge‐fused R₂²(8) and R₂²(20) rings. This study illustrates both the readiness with which highly‐substituted pyrimidine rings can be distorted from planarity and the significant differences between the supramolecular aggregation in two rather similar compounds.     

Hydrogen‐bonding patterns in rac‐1‐acetyl‐5‐methyl‐2‐thioxoimidazolidin‐4‐one

In the title compound, C₆H₈N₂O₂S, also known as N‐acetyl‐2‐thiohydantoin–alanine, the molecules are joined by N—H...O hydrogen bonds, forming centrosymmetric R₂²(8) dimers; these dimers are linked by C—H...O interactions to form R₂²(10) rings, thus forming C₂²(10) chains that run along the [101] direction.     

[2 + 3]‐Cycloadditions of Phosphonodithioformate S‐Methanides with CS,NN,and CC Dipolarophiles

The reaction of the methyl (dialkoxyphosphinyl)‐dithioformates (= methyl dialkoxyphosphinecarbodithioate 1‐oxides) 10 with CH₂N₂ at − 65° in THF yielded cycloadducts which eliminated N₂ between − 40 and − 35° to give the corresponding phosphonodithioformate S‐methanides ( =methylenesulfonium (dialkoxyoxidophosphino)(methylthio)methylides) 11 (Scheme 3). These reactive 1,3‐dipoles were intercepted by aromatic thioketones to yield 1,3‐dithiolanes. Whereas the reaction with thiobenzophenone ( 12b ) led to the sterically more congested isomers 15 regioselectively, a mixture of both regioisomers was obtained with 9H‐fluorene‐9‐thione ( 12a ). Trapping of 11 with phosphono‐ and sulfonodithioformates led exclusively to the sterically less hindered 1,3‐dithiolanes 16 and 18 , respectively (Scheme 4). In addition, reactive CC dipolarophiles such as ethenetetracarbonitrile, maleic anhydride, and N‐phenylmaleimide as well as the NN dipolarophile dimethyl diazenedicarboxylate were shown to be efficient interceptors of 11 (Scheme 5).     

Convenient Entry to α‐Amino‐β‐hydroxy‐γ‐methyl Carboxylic Acids. Diastereoselective Formation and Directed Homogeneous Hydrogenation of 3‐(3‐Aryl‐1‐hydroxy‐2‐methylprop‐2‐enyl)‐1,4‐benzodiazepin‐2‐ones

Aldol reaction of 7‐chloro‐1,3‐dihydro‐1‐methyl‐5‐phenyl‐2H‐1,4‐benzodiazepin‐2‐one ( 1 ) with 4‐substituted α‐methylcinnamaldehydes 2 – 5 afforded a mixture of threo‐ and erythro‐3‐(3‐aryl‐1‐hydroxy‐2‐methylprop‐2‐enyl)‐7‐chloro‐1,3‐dihydro‐1‐methyl‐5‐phenyl‐2H‐1,4‐benzodiazepin‐2‐ones 6 – 13 . The chromatographically separated threo diastereoisomers 6, 8, 10 , and 12 and erythro diastereoisomers 7, 9, 11 , and 13 were submitted to ‘directed' homogeneous hydrogenation catalyzed by [Rh^I(cod)(diphos‐4)]ClO₄ (cod=cycloocta‐1,5‐diene, diphos‐4=butane‐1,4‐diylbis[diphenylphosphine]. From the erythro‐racemates 9, 11 , and 13 , the erythro,erythro/erythro,threo‐diastereoisomer mixtures 16 / 17, 20 / 21 , and 24 / 25 were obtained in ratios of 20 : 80 to 28 : 72 (HPLC), which were separated by chromatography. From the threo racemates 8, 10 , and 12 , the threo,threo/threo,erythro‐diastereoisomer mixtures were obtained in a ratio of ca. 25 : 75 (¹H‐NMR). The relative configurations were assigned by means of ¹H‐NMR data and X‐ray crystal‐structure determination of 21 . Hydrolysis of 21 afforded the diastereoisomerically pure N‐(benzyloxy)carbonyl derivative 27 of α‐amino‐β‐hydroxy‐γ‐methylpentanoic acid 26 , representative of the novel group of polysubstituted α‐amino‐β‐hydroxycarboxylic acids.     

2,3‐Dihydro‐1,3‐benzothiazol‐2‐iminium monohydrogen sulfate and 2‐iminio‐2,3‐dihydro‐1,3‐benzothiazole‐6‐sulfonate: a combined structural and theoretical study

The 2‐aminobenzothiazole sulfonation intermediate 2,3‐dihydro‐1,3‐benzothiazol‐2‐iminium monohydrogen sulfate, C₇H₇N₂S⁺·HSO₄⁻, (I), and the final product 2‐iminio‐2,3‐dihydro‐1,3‐benzothiazole‐6‐sulfonate, C₇H₆N₂O₃S₂, (II), both have the endocyclic N atom protonated; compound (I) exists as an ion pair and (II) forms a zwitterion. Intermolecular N—H...O and O—H...O hydrogen bonds are seen in both structures, with bonding energy (calculated on the basis of density functional theory) ranging from 1.06 to 14.15 kcal mol⁻¹. Hydrogen bonding in (I) and (II) creates DDDD and C(8)C(9)C(9) first‐level graph sets, respectively. Face‐to‐face stacking interactions are observed in both (I) and (II), but they are extremely weak.     

Two derivatives of 1,5‐disubstituted tetrazoles: 1‐(4‐nitrophenyl)‐1H‐tetrazol‐5‐amine and {(E)‐[1‐(4‐ethoxyphenyl)‐1H‐tetrazol‐5‐yl]iminomethyl}dimethylamine

The geometric features of 1‐(4‐nitrophenyl)‐1H‐tetrazol‐5‐amine, C₇H₆N₆O₂, correspond to the presence of the essential interaction of the 5‐amino group lone pair with the π system of the tetrazole ring. Intermolecular N—H...N and N—H...O hydrogen bonds result in the formation of infinite chains running along the [110] direction and involve centrosymmetric ring structures with motifs R₂²(8) and R₂²(20). Molecules of {(E)‐[1‐(4‐ethoxyphenyl)‐1H‐tetrazol‐5‐yl]iminomethyl}dimethylamine, C₁₂H₁₆N₆O, are essentially flattened, which facilitates the formation of a conjugated system spanning the whole molecule. Conjugation in the azomethine N=C—N fragment results in practically the same length for the formal double and single bonds.     

New electron‐deficient chiral phosphines: (4R,5R)‐1,3‐bis(trifluoromethanesulfonyl)perhydro‐1,3,2‐benzodiazaphosphol‐2‐yl] substituted amines

Three chiral electron‐deficient phosphine ligands, [(4R,15R)‐,3‐bis­(tri­fluoro­methane­sulfonyl)­per­hydro‐1,3,2‐benzodiazaphosphol‐2‐yl]­diethyl­amine, C₁₂H₂₀F₆N₃O₄PS₂, (IIIa), [(4R,5R)‐1,3‐bis­(tri­fluoro­methane­sulfonyl)­per­hydro‐1,3,2‐benzodi­aza­phosphol‐2‐yl]­di­methyl­amine, C₁₀H₁₆F₆N₃O₄PS₂, (IIIb), and bis­[(4R,5R)‐1,3‐bis­(tri­fluoro­methane­sulfonyl)­per­hydro‐1,3,2‐benzodi­aza­phosphol‐2‐yl]­methyl­amine, (IV), as the chloroform solvate, C₁₇H₂₃F₁₂N₅O₈P₂S₄·0.98CHCl₃, have been prepared from (1R,2R)‐N,N′‐bis­(tri­fluoro­methane­sulfonyl)‐1,2‐cyclo­hexane­di­amine and diethyl phosphor­amido­us dichloride, dimethyl phosphoramidous dichloride or methyl imidodi­phosphorus tetrachloride. The π‐acceptor abilities of these new types of ligands have been evaluated by X‐ray determination of the P—N bond lengths; it has been found that the most promising ligand is the bis­(phosphine) (IV).     

Weak C—H...O and C—H...π hydrogen bonds and π–π stacking interactions in a series of four N′‐[(E)‐(aryl)methylidene]‐N‐methyl‐2‐oxo‐1,3‐oxazolidine‐4‐carbohydrazides

Oxazolidin‐2‐ones are widely used as protective groups for 1,2‐amino alcohols and chiral derivatives are employed as chiral auxiliaries. The crystal structures of four differently substituted oxazolidinecarbohydrazides, namely N′‐[(E)‐benzylidene]‐N‐methyl‐2‐oxo‐1,3‐oxazolidine‐4‐carbohydrazide, C₁₂H₁₂N₃O₃, (I), N′‐[(E)‐2‐chlorobenzylidene]‐N‐methyl‐2‐oxo‐1,3‐oxazolidine‐4‐carbohydrazide, C₁₂H₁₂ClN₃O₃, (II), (4S)‐N′‐[(E)‐4‐chlorobenzylidene]‐N‐methyl‐2‐oxo‐1,3‐oxazolidine‐4‐carbohydrazide, C₁₂H₁₂ClN₃O₃, (III), and (4S)‐N′‐[(E)‐2,6‐dichlorobenzylidene]‐N,3‐dimethyl‐2‐oxo‐1,3‐oxazolidine‐4‐carbohydrazide, C₁₃H₁₃Cl₂N₃O₃, (IV), show that an unexpected mild‐condition racemization from the chiral starting materials has occurred in (I) and (II). In the extended structures, the centrosymmetric phases, which each crystallize with two molecules (A and B) in the asymmetric unit, form A+B dimers linked by pairs of N—H...O hydrogen bonds, albeit with different O‐atom acceptors. One dimer is composed of one molecule with an S configuration for its stereogenic centre and the other with an R configuration, and possesses approximate local inversion symmetry. The other dimer consists of either R,R or S,S pairs and possesses approximate local twofold symmetry. In the chiral structure, N—H...O hydrogen bonds link the molecules into C(5) chains, with adjacent molecules related by a 2₁ screw axis. A wide variety of weak interactions, including C—H...O, C—H...Cl, C—H...π and π–π stacking interactions, occur in these structures, but there is little conformity between them.     

Investigation of the C−H Activation Potential of [Hydrotris(1H‐pyrazolato‐κN1)borato(1−)]iridium (IrTpx) Fragments Featuring Aromatic Substituents x at the 3‐Position of the Pyrazole Rings,The Choice of the Precursor

A series of pyrazole‐substituted [hydrotris(1H‐pyrazolato‐κN¹)borato(1−)]iridium complexes of the general composition [Ir(Tp^x)(olefin)₂] (Tp^x=Tp^Ph and Tp^Th) and their capability to activate C−H bonds is presented. As a test reaction, the double C−H activation of cyclic‐ether substrates leading to the corresponding Fischer carbene complexes was chosen. Under the reaction conditions employed, the parent compound [Ir(Tp^Ph)(ethene)₂] was not isolable; instead, (OC‐6‐25)‐[Ir(Tp^PhκC^Ph,κ³N,N′,N″)(ethyl)(η²‐ethene)] ( 1 ) was formed diastereoselectively. Upon further heating, 1 could be converted exclusively to (OC‐6‐24)‐[Ir(Tp^Phκ²C^Ph,C^Ph,κ³N,N′,N″)(η²‐ethene)] ( 2 ). Complex 1 , but not 2 , reacted with THF to give (OC‐6‐35)‐[Ir(Tp^Phκ³N,N′,N″)H(dihydrofuran‐2(3H)‐ylidene)] ( 3 ), a cyclic Fischer carbene formed by double C−H activation of THF. Accordingly, complexes of the general formula [Ir(Tp^x)(butadiene)] (see 4 – 6 ; butadiene=buta‐1,3‐diene, 2‐methylbuta‐1,3‐diene (isoprene), 2,3‐dimethylbuta‐1,3‐diene) reacted with THF to yield 3 or the related derivative 9 . The reaction rate was strongly dependent on the steric demand of the butadiene ligand and the nature of the substituent at the 3‐position of the pyrazole rings.     

N—H⋯N and C—H⋯π inter­actions in 4‐amino‐3‐methyl‐5‐(p‐tol­yl)‐4H‐1,2,4‐triazole and 4‐amino‐3‐methyl‐5‐phenyl‐4H‐1,2,4‐triazole

The title compounds, C₁₀H₁₂N₄, (I), and C₉H₁₀N₄, (II), have been synthesized and characterized both spectroscopically and structurally. The dihedral angles between the triazole and benzene ring planes are 26.59 (9) and 42.34 (2)°, respectively. In (I), mol­ecules are linked principally by N—H⋯N hydrogen bonds involving the amino NH₂ group and a triazole N atom, forming R₄⁴(20) and R₂⁴(10) rings which link to give a three‐dimensional network of mol­ecules. The hydrogen bonding is supported by two different C—H⋯π inter­actions from the tolyl ring to either a triazole ring or a tolyl ring in neighboring mol­ecules. In (II), inter­molecular hydrogen bonds and C—H⋯π inter­actions produce R₃⁴(15) and R₄⁴(21) rings.     

On Alkylideneamidosulfenyl Chlorides and 1‐Thia‐2‐azoniaallene Salts

X‐Ray‐diffraction analysis of ^tBu₂CN SCl ( 4b ) revealed an almost linear CNS unit with an SN bond order of ca. 1.9 (Fig. 1), in agreement with the structure of a 1‐thia‐2‐azoniaallene chloride. With SCl₂ and SbCl₅, compound 4b was transformed into the imidosulfurous dichloride 6 (Scheme 2). With morpholine, compounds 4b and 6 afforded the sulfenamide 7 and the aminosulfonium salt 8 , respectively. The (diarylmethylene)amidosulfenyl chlorides 4g , h , i reacted with SbCl₅ to give SbCl salts of the 1,2‐benzisothiazoles 9a , b , d , most likely via 1‐thia‐2‐azoniaallene intermediates 2 (Scheme 3).     

1‐(2‐Cyclohex‐2‐enylpropionyl)‐3‐methylurea, 2‐ethyl‐5‐methylhexanamide and 2‐ethylpentanamide: three products of barbiturate decomposition

The three title compounds were obtained by reactions which mimic, with more extreme conditions, the in vivo metabolism of barbiturates. 1‐(2‐Cyclohex‐2‐enylpropionyl)‐3‐methylurea, C₁₁H₁₈N₂O₂, (I), and 2‐ethylpentanamide, C₈H₁₇NO, (III), both crystallize with two unique molecules in the asymmetric unit; in the case of (III), one unique molecule exhibits whole‐molecule disorder. 2‐Ethyl‐5‐methylhexanamide, C₉H₁₉NO, (II), crystallizes as a fully ordered molecule with Z′ = 1. In the crystal structures, three different hydrogen‐bonding motifs are observed: in (I) a combination of R₂²(4) and R₂²(8) motifs, and in (II) and (III) a combination of R₄²(8) and R₂²(8) motifs. In all three structures, one‐dimensional ribbons are formed by N—H...O hydrogen‐bonding interactions.     

Electrophilic Reactivities of 1,2‐Diaza‐1,3‐dienes

The kinetics of the reactions of 1,2‐diaza‐1,3‐dienes 1 with acceptor‐substituted carbanions 2 have been studied at 20 °C. The reactions follow a second‐order rate law, and can be described by the linear free energy relationship log k(20 °C)=s(N+E) [Eq. (1)]. With Equation (1) and the known nucleophile‐specific parameters N and s for the carbanions, the electrophilicity parameters E of the 1,2‐diaza‐1,3‐dienes 1 were determined. With E parameters in the range of ?13.3 to ?15.4, the electrophilic reactivities of 1 a–d are comparable to those of benzylidenemalononitriles, 2‐benzylideneindan‐1,3‐diones, and benzylidenebarbituric acids. The experimental second‐order rate constants for the reactions of 1 a – d with amines 3 and triarylphosphines 4 agreed with those calculated from E, N, and s, indicating the applicability of the linear free energy relationship [Eq. (1)] for predicting potential nucleophilic reaction partners of 1,2‐diaza‐1,3‐dienes 1 . Enamines 5 react up to 10² to 10³ times faster with compounds 1 than predicted by Equation (1), indicating a change of mechanism, which becomes obvious in the reactions of 1 with enol ethers.     

[N,N′‐Bis­(salicyl­idene)‐2,2‐di­methyl‐1,3‐propane­diaminato]­nickel(II) and [N,N′‐bis­(salicyl­idene)‐2,2‐di­methyl‐1,3‐propane­diaminato]copper(II)

In the title compounds, {2,2′‐[2,2‐di­methyl‐1,3‐propane­diyl­bis­(nitrilo­methyl­idyne)]­diphenolato‐κ⁴N,N′,O,O′}nickel(II), [Ni(C₁₉H₂₀N₂O₂)], and {2,2′‐[2,2‐di­methyl‐1,3‐propane­diyl­bis­(nitrilo­methyl­idyne)]­diphenolato‐κ⁴N,N′,O,O′}copper(II), [Cu(C₁₉H₂₀N₂O₂)], the Ni^II and Cu^II atoms are coordinated by two iminic N and two phenolic O atoms of the N,N′‐bis­(salicyl­idene)‐2,2‐di­methyl‐1,3‐propane­diaminate (SALPD^2?, C₁₇H₁₆N₂O₂^2?) ligand. The geometry of the coordination sphere is planar in the case of the Ni^II complex and distorted towards tetrahedral for the Cu^II complex. Both complexes have a cis configuration imposed by the chelate ligand. The dihedral angles between the N/Ni/O and N/Cu/O coordination planes are 17.20 (6) and 35.13 (7)°, respectively.     

4‐(3‐Azaniumylpropyl)morpholin‐4‐ium chloride hydrogen oxalate: an unusual example of a dication with different counter‐anions

The mixed organic–inorganic title salt, C₇H₁₈N₂O²⁺·C₂HO₄⁻·Cl⁻, forms an assembly of ionic components which are stabilized through a series of hydrogen bonds and charge‐assisted intermolecular interactions. The title assembly crystallizes in the monoclinic C2/c space group with Z = 8. The asymmetric unit consists of a 4‐(3‐azaniumylpropyl)morpholin‐4‐ium dication, a hydrogen oxalate counter‐anion and an inorganic chloride counter‐anion. The organic cations and anions are connected through a network of N—H...O, O—H...O and C—H...O hydrogen bonds, forming several intermolecular rings that can be described by the graph‐set notations R₃³(13), R₂¹(5), R₁²(5), R₂¹(6), R₂³(6), R₂²(8) and R₃³(9). The 4‐(3‐azaniumylpropyl)morpholin‐4‐ium dications are interconnected through N—H...O hydrogen bonds, forming C(9) chains that run diagonally along the ab face. Furthermore, the hydrogen oxalate anions are interconnected via O—H...O hydrogen bonds, forming head‐to‐tail C(5) chains along the crystallographic b axis. The two types of chains are linked through additional N—H...O and O—H...O hydrogen bonds, and the hydrogen oxalate chains are sandwiched by the 4‐(3‐azaniumylpropyl)morpholin‐4‐ium chains, forming organic layers that are separated by the chloride anions. Finally, the layered three‐dimensional structure is stabilized via intermolecular N—H...Cl and C—H...Cl interactions.     

A novel 18‐membered metallocycle in {2,5‐bis[3‐(1H‐1,3‐imidazol‐1‐ylmethyl)phenyl]‐1,3,4‐oxadiazole}dichloridocobalt(II)

The title molecular complex, [CoCl₂(C₂₂H₁₈N₆O)], features a novel 18‐membered Co‐containing metallocycle. The Co^II atom lies in a fairly regular tetrahedral geometry defined by two imidazole N‐atom donors from one 2,5‐bis[3‐(1H‐1,3‐imidazol‐1‐ylmethyl)phenyl]‐1,3,4‐oxadiazole (L) ligand and two chloride anions. The coordinating orientation of the L ligand plays an important role in constructing the metallocycle complex. The complexes form a three‐dimensional supramolecular assembly via nonclassical C—H...Cl and C—H...N hydrogen bonds and π–π interactions.     

3‐Nitrophenol–4,4′‐bipyridyl N,N′‐dioxide (2/1): a DFT study and CSD analysis of DPNO molecular complexes

The title 2:1 complex of 3‐nitrophenol (MNP) and 4,4′‐bipyridyl N,N′‐dioxide (DPNO), 2C₆H₅NO₃·C₁₀H₈N₂O₂ or 2MNP·DPNO, crystallizes as a centrosymmetric three‐component adduct with a dihedral angle of 59.40 (8)° between the planes of the benzene rings of MNP and DPNO (the DPNO moiety lies across a crystallographic inversion centre located at the mid‐point of the C—C bond linking its aromatic rings). The complex owes its formation to O—H...O hydrogen bonds [O...O = 2.605 (3) Å]. Molecules are linked by intermolecular C—H...O and C—H...N interactions forming R₂¹(6) and R₂²(10) rings, and R₆⁶(34) and R₄⁴(26) macro‐rings, all of which are aligned along the [01] direction, and R₂²(10) and R₂¹(7) rings aligned along the [010] direction. The combination of chains of rings along the [01] and [010] directions generates the three‐dimensional structure. A total of 27 systems containing the DNPO molecule and forming molecular complexes of an organic nature were analysed and compared with the structural characteristics of the dioxide reported here. The N—O distance [1.325 (2) Å] depends not only on the interactions involving the O atom at the N—O group, but also on the structural ordering and additional three‐dimensional interactions in the crystal structure. A density functional theory (DFT) optimized structure at the B3LYP/6‐311G(d,p) level is compared with the molecular structure in the solid state.     

[(1R,2R)‐1,2‐Di­amino­cyclo­hexane‐κ2N,N′](α‐di­imine‐κ2N,N′)­platinum(II) bis­(hexa­fluoro­phosphate), where α‐di­imine is 2,2′‐bi­pyridine and 1,10‐phen­anthroline

The title Pt^II complexes, viz. (2,2′‐bi­pyridine‐κ²N,N′)[(1R,2R)‐1,2‐di­amino­cyclo­hexane‐κ²N,N′]­platinum(II) bis­(hexa­fluoro­phosphate), [Pt(C₆H₁₄N₂)(C₁₀H₈N₂)](PF₆)₂, and [(1R,2R)‐1,2‐di­amino­cyclo­hexane‐κ²N,N′](1,10‐phenanthroline‐κ²N,N′)platinum(II) bis­(hexa­fluoro­phosphate), [Pt(C₆H₁₄N₂)(C₁₂H₈N₂)](PF₆)₂, containing an aromatic α‐di­imine and a non‐planar di­amino­cyclo­hexane, both form a ladder‐type structure, which is constructed via loose π–π stacking on the α‐di­imine ligands and hydrogen bonding between the cyclic amines and the counter‐anions. In the former compound, there are two independent complex cations, both of which have a twofold axis through the Pt atom.     

Synthesis of optically active af‐(1‐Ethyl‐3‐methylhexahydro‐1,3‐diazin‐5‐yl)‐ and N‐(1‐Ethyl‐5‐methyloctahydro‐1,5‐diazocin‐3‐yl)pyridine‐3‐carboxamides

As part of the structure‐activity relationship of the dopamine D₂ and serotonin 5‐HT₃ receptors antagonist 1, which is a clinical candidate with a broad antiemetic activity, the synthesis and dopamine D₂ and serotonin 5‐HT₃ receptors binding affinity of (R)‐5‐bromo‐N‐(1‐ethyl‐3‐methylhexahydro‐1,3‐diazin‐5‐yl)‐ and (R)‐5‐bromo‐N‐(1‐ethyl‐5‐methyloctahydro‐1,5‐diazocin‐3‐yl)‐2‐methoxy‐6‐methylaminopyridine‐3‐carboxam‐ides ( 2 and 3 ) are described. Treatment of 1‐ethyl‐2‐(p‐toluenesulfonyl)amino‐3‐methylaminopropane dihy‐drochloride ( 4a ) with paraformaldehyde and successive deprotection gave the 5‐aminohexahydro‐1,3‐diazine 6 in excellent yield. 3‐Amino‐1‐ethyl‐5‐methyloctahydro‐1,5‐diazocine ( 15 ) was prepared from 2‐(benzyloxycarbonyl)amino‐3‐[[N‐(tert‐butoxycarbonyl)‐N‐methyl]amino]‐1‐ethylaminopropane ( 9 ) through the intramolecular amidation of (R)‐3‐[N‐[(2‐benzyloxycarbonylamino‐3‐methylamino)propyl]‐N‐ethyl]aminopropionic acid trifluoroacetate ( 12 ), followed by lithium aluminum hydride reduction of the resulting 6‐oxo‐1‐ethyl‐5‐methyloctahydrodiazocine ( 13 ) in 41% yield. Reaction of the amines 6 and 15 with 5‐bromo‐2‐methoxy‐6‐methylaminopyridine‐3‐carboxylic acid furnished the desired 2 and 3 , which showed much less potent affinity for dopamine D₂ receptors than 1 .