Reactive properties of trans-dichlorooxirane in relation to the contrasting carcinogenicities of vinyl chloride and trans-dichloroethylen

Our objective in this work is to gain insight into the contrasting carcinogenic activities of vinyl chloride (definitely carcinogenic) and trans-dichloroethylene (apparently inactive). The initial metabolic step for each molecule is believed to be epoxidation of the double bond, and there is evidence indicating that for vinyl chloride, this epoxide (chlorooxirane) is its ultimate (direct-acting) carcinogenic form. This article presents the findings of a computational study of the reactive properties of trans-dichlorooxirane (the epoxide of trans-dichloroethylene). An ab initio SCF -MO procedure was used to determine the energy requirements for stretching the C? O and C? Cl bonds (S_N1 reactivity) and to study the epoxide's S_N2 interactions with ammonia, taken as a model nucleophile. The starting points were the oxygen- and chlorine-protonated forms of the epoxide. The structure of the system was reoptimized at each step along the various reaction pathways. The results of this work are compared to an analogous earlier study of the reactive properties of chlorooxirane. The chlorineprotonated C? Cl bonds are found to have much lower energy barriers to stretching than do the oxygen-protonated C? O bonds. In the S_N2 processes, intermediate complexes are formed with ammonia by both the oxygen- and the chlorine-protonated epoxides; the latter complexes are the more stable. Based on our results, we propose two mechanisms (one S_N1 and the other S_N2) whereby trans-dichlorooxirane can interact with N₇ of guanine to produce an adduct analogous to one formed by chlorooxirane, which has been found to be the primary in vivo DNA alkylation product of vinyl chloride and to which has been attributed the carcinogenicity of the latter. Overall, trans-dichlorooxirane is found to be chemically more reactive than chlorooxirane; this may help to account for the much lesser carcinogenic and mutagenic activities of trans-dichloroethylene, since the epoxide may be reacting with other cellular nucleophiles before it reaches the key site(s) at which the carcinogenic or mutagenic interaction would occur. We also offer some speculations concerning other possible factors related to the differing carcinogenicities of vinyl chloride and trans-dichloroethylene, such as ease of epoxide formation and the likelihood of oxygen protonation.     

Some reactive properties of chlorooxirane,a likely carcinogenic metabolite of vinyl chloride

We have carried out a computational study of the reactive properties of chlorooxirane, the metabolically produced epoxide of vinyl chloride that is believed to be a direct-acting carcinogenic form of this molecule. An ab initio SCF-MO procedure (GAUSSIAN 70) was used to compute the energy requirements for stretching the C? Cl and both C? O bonds (S_N 1 reactivity) and to determine the course of the epoxide's possible S_N 2 reactions with ammonia, taken as a model for nucleophilic sites on DNA. The epoxide was assumed to be protonated; both the oxygen- and chloro-protonated forms were considered. At each step along the various reaction pathways, the structure of the system was reoptimized. For the oxygen-protonated epoxide, the C₁? O bond has a significantly lower energy barrier to stretching than does the C₂? O. (The carbon bearing the chlorine is designated C₁.) However, both are very much higher than that of the C? Cl bond in the chloro-protonated form, confirming our earlier finding of the relative weakness of this bond. In the S_N 2 processes involving ammonia, intermediate complexes are formed with both carbons of the oxygen-protonated epoxide, the C₂-complex being the more stable. However, the most stable ammonia complex occurs at C₁ of the chloro-protonated epoxide. Our calculated results, both the energies and also the geometry changes, allow us to propose two possible mechanisms for the formation of the 7-N-(2-oxoethyl) derivative of guanine that has been observed to be the major in vivo DNA alkylation product of vinyl chloride and has been suggested as possibly being responsible for its carcinogenicity. One of these mechanisms is S_N 1 and starts with the chloro-protonated epoxide; the other is S_N 2 and involves the oxygen-protonated form.     

Chiral Primary‐Amine‐Catalyzed Conjugate Addition to α‐Substituted Vinyl Ketones/Aldehydes: Divergent Stereocontrol Modes on Enamine Protonation

Enantioselective protonation with a catalytic enamine intermediate represents a challenging, yet fundamentally important process for the synthesis of α‐chiral carbonyls. We describe herein chiral primary‐amine‐catalyzed conjugate additions of indoles to both α‐substituted acroleins and vinyl ketones. These reactions feature enamine protonation as the stereogenic step. A simple primary–tertiary vicinal diamine 1 with trifluoromethanesulfonic acid (TfOH) was found to enable both of the reactions of acroleins and vinyl ketones with good activity and high enantioselectivity. Detailed mechanistic studies reveal that these reactions are rate‐limiting in iminium formation and they all involve a uniform H₂O/acid‐bridged proton transfer in the stereogenic steps but divergent stereocontrol modes for the protonation stereoselectivity. For the reactions of α‐branched acroleins, facial selections on H₂O‐bridged protonation determine the enantioselectivity, which is enhanced by an OH???π interaction with indole as uncovered by DFT calculations. On the other hand, the stereoselectivity of the reactions with vinyl ketones is controlled according to the Curtin–Hammett principle in the C? C bond‐formation step, which precedes a highly stereospecific enamine protonation.     

Competitive Bond Rupture in the Photodissociation of Bromoacetyl Chloride and 2‐ and 3‐Bromopropionyl Chloride: Adiabatic versus Diabatic Dissociation

Competitive bond dissociation mechanisms for bromoacetyl chloride and 2‐ and 3‐bromopropionyl chloride following the ¹[n(O)→π*(C?O)] transition at 234–235 nm are investigated. Branching ratios for C? Br/C? Cl bond fission are found by using the (2+1) resonance‐enhanced multiphoton ionization (REMPI) technique coupled with velocity ion imaging. The fragment branching ratios depend mainly on the dissociation pathways and the distances between the orbitals of Br and the C?O chromophore. C? Cl bond fission is anticipated to follow an adiabatic potential surface for a strong diabatic coupling between the n(O)π*(C?O) and n_p(Cl)σ*(C? Cl) bands. In contrast, C? Br bond fission is subject to much weaker coupling between n(O)π*(C?O) and n_p(Br)σ*(C? Br). Thus, a diabatic pathway is preferred for bromoacetyl chloride and 2‐bromopropionyl chloride, which leads to excited‐state products. For 3‐bromopropionyl chloride, the available energy is not high enough to reach the excited‐state products such that C? Br bond fission must proceed through an adiabatic pathway with severe suppression by nonadiabatic coupling. The fragment translational energies and anisotropy parameters for the three molecules are also analyzed and appropriately interpreted.     

The Mechanism of NO Bond Cleavage in Rhodium‐Catalyzed CH Bond Functionalization of Quinoline N‐oxides with Alkynes: A Computational Study

Metal‐catalyzed C?H activation not only offers important strategies to construct new bonds, it also allows the merge of important research areas. When quinoline N‐oxide is used as an arene source in C?H activation studies, the N?O bond can act as a directing group as well as an O‐atom donor. The newly reported density functional theory method, M11L, has been used to elucidate the mechanistic details of the coupling between quinoline N?O bond and alkynes, which results in C?H activation and O‐atom transfer. The computational results indicated that the most favorable pathway involves an electrophilic deprotonation, an insertion of an acetylene group into a Rh?C bond, a reductive elimination to form an oxazinoquinolinium‐coordinated Rh^I intermediate, an oxidative addition to break the N?O bond, and a protonation reaction to regenerate the active catalyst. The regioselectivity of the reaction has also been studied by using prop‐1‐yn‐1‐ylbenzene as a model unsymmetrical substrate. Theoretical calculations suggested that 1‐phenyl‐2‐quinolinylpropanone would be the major product because of better conjugation between the phenyl group and enolate moiety in the corresponding transition state of the regioselectivity‐determining step. These calculated data are consistent with the experimental observations.     

Site selectivity in the protonation of a phosphinito bridged Pt(I)-Pt(I) complex: a combined NMR and density-functional theory mechanistic study

The protonation of the dinuclear phosphinito bridged complex [(PHCy2)Pt(mu-PCy2){kappa(2)P,O-mu-P(O)Cy2}Pt(PHCy2)] (Pt-Pt) (1) by Br?nsted acids affords hydrido bridged Pt-Pt species the structure of which depends on the nature and on the amount of the acid used. The addition of 1 equiv of HX (X = Cl, Br, I) gives products of formal protonation of the Pt-Pt bond of formula syn-[(PHCy2)(X)Pt(mu-PCy2)(mu-H)Pt(PHCy2){kappaP-P(O)Cy2}] (Pt-Pt) (5, X = Cl; 6, X = Br; 8, X = I), containing a Pt-X bond and a dangling kappa P-P(O)Cy2 ligand. Uptake of a second equivalent of HX results in the protonation of the P(O)Cy2 ligand with formation of the complexes [(PHCy2)(X)Pt(mu-PCy2)(mu-H)Pt(PHCy2){kappaP-P(OH)Cy2}]X (Pt-Pt) (3, X = Cl; 4, X = Br; 9, X = I). Each step of protonation is reversible, thus reactions of 3, 4, with NaOH give, first, the corresponding neutral complexes 5, 6, and then the parent compound 1. While the complexes 3 and 4 are indefinitely stable, the iodine analogue 9 transforms into anti-[(PHCy2)(I)Pt(mu-PCy2)(mu-H)Pt(PHCy2)(I)] (Pt-Pt) (7) deriving from substitution of an iodo group for the P(OH)Cy2 ligand. Complexes 3 and 4 are isomorphous crystallizing in the triclinic space group P1 and show an intramolecular hydrogen bond and an interaction between the halide counteranion and the POH hydrogen. The occurrence of such an interaction also in solution was ascertained for 3 by (35)Cl NMR. Multinuclear NMR spectroscopy (including (31)P-(1)H HOESY) and density-functional theory calculations indicate that the mechanism of the reaction starts with a prior protonation of the oxygen with formation of an intermediate (12) endowed with a six membered Pt(1)-X...H-O-P-Pt(2) ring that evolves into thermodynamically stable products featuring the hydride ligand bridging the Pt atoms. Energy profiles calculated for the various steps of the reaction between 1 and HCl showed very low barriers for the proton transfer and the subsequent rearrangement to 12, while a barrier of 29 kcal mol(-1) was found for the transformation of 12 into 5.     

Conformational properties of polar polymers. I. Poly(vinyl chloride)

A recently developed method for including polar bonds in conformational energy calculations is applied to poly(vinyl chloride). Inductive effects on dipole moments and the effects of intervening atoms on electrostatic interaction energies are represented by polarizability centers in conjunction with bond centered dipoles. Solvation energies are estimated by means of a continuum dipole–quadrupole electrostatic model. Calculated energies of a number of conformations of meso and racemic 2,4-dichloropentane and the iso, syndio, and hetero forms of 2,4,6-trichloroheptane give satisfactory representations of isomer and conformer populations. Electrostatic effects are found to be quite important. However they appear to be effectively of sufficiently short range that the calculated conformer energies are found to be fit well by a linear combination of interaction parameters (consisting of gauche, skew chlorine, four-bond CH₂…CH₂, CH₂…Cl, and Cl…Cl interactions) conventional to vinyl polymers and a special four-bond interaction that arises when the bond sequence Cl? CH? CH²? CH? Cl is (nearly) coplanar. These interaction parameters when assembled into statistical weight matrices lead to calculated values of both the characteristic ratio and the dipole moment ratio in satisfactory agreement with experiment. Least energy paths for transitions between the most stable conformations are also calculated.     

Protonation Switching to the Least‐Basic Heteroatom of Carbamate through Cationic Hydrogen Bonding Promotes the Formation of Isocyanate Cations

We found that phenethylcarbamates that bear ortho‐salicylate as an ether group (carbamoyl salicylates) dramatically accelerate O?C bond dissociation in strong acid to facilitate generation of isocyanate cation (N‐protonated isocyanates), which undergo subsequent intramolecular aromatic electrophilic cyclization to give dihydroisoquinolones. To generate isocyanate cations from carbamates in acidic media as electrophiles for aromatic substitution, protonation at the ether oxygen, the least basic heteroatom, is essential to promote C?O bond cleavage. However, the carbonyl oxygen of carbamates, the most basic site, is protonated exclusively in strong acids. We found that the protonation site can be shifted to an alternative basic atom by linking methyl salicylate to the ether oxygen of carbamate. The methyl ester oxygen ortho to the phenolic (ether) oxygen of salicylate is as basic as the carbamate carbonyl oxygen, and we found that monoprotonation at the methyl ester oxygen in strong acid resulted in the formation of an intramolecular cationic hydrogen bond (>C?O⁺?H???O<) with the phenolic ether oxygen. This facilitates O?C bond dissociation of phenethylcarbamates, thereby promoting isocyanate cation formation. In contrast, superacid‐mediated diprotonation at the methyl ester oxygen of the salicylate and the carbonyl oxygen of the carbamate afforded a rather stable dication, which did not readily undergo C?O bond dissociation. This is an unprecedented and unknown case in which the monocation has greater reactivity than the dication.     

Vinyl polymerization initiated by system of organic halides and tertiary amines

A study of the polymerization of vinyl monomers with binary systems of tertiary amines and various organic halides containing chemical bonds such as C? Cl, N? Cl, O? Cl, S? Cl, and Si? Cl has been made at 60°C. Some of the binary systems were found to be effective as radical initiator in the polymerization of methyl methacrylate. The relative initiating activities of the halides in the presence of dimethylaniline were found to be in the following order: tert-C₄H₉OCl > n-C₄H₉NCl₂ > (n-C₄H₉)₂NCl ? CH₃SiCl₃ ? C₆H₅SiCl₃ > C₆H₅SO₂Cl > C₆H₅Cl > C₆H₅PCl₂. Styrene and vinyl acetate polymerized only with the initiator system of dimethylaniline and benzyl chloride. Tri-n-butylamine was less active than dimethylaniline. Pyridine and 4-vinylpyridine, in combination with some organic halides, also initiated the polymerization of methyl methacrylate. The N-vinylcarbazole–benzenesulfonyl chloride system, in the presence of methyl methacrylate, gave only the homopolymer of N-vinylcarbazole.     

Determination of tacticity in poly(vinyl chloride) by infrared spectroscopy

From the temperature dependence of infrared spectra of poly(vinyl chloride) samples prepared by different methods, the intensity of the band at 690 cm.¹ (proportional to the number of isotactic diads in the sample), as well as that of the tacticity-independent C? H stretching band, was found to be independent of the crystallinity of the sample. These lines were therefore applied for the tacticity determination in poly(vinyl chloride), measured in the form of KBr pellets. The numerical tacticity value was obtained from the known values of absorbance coefficients of SCH and SHH type C? Cl stretching bands in solution, and from the shape of the spectrum.     

IR laser ablation of poly(vinyl chloride): Formation of monomer and deposition of nanofibres of chlorinated polyhydrocarbon

IR laser-induced ablation of poly(vinyl chloride) was examined under different irradiation conditions and its volatile and solid products were characterized by mass, infrared, UV and X-ray photoelectron spectroscopy, electron microscopy and thermogravimetry. It is demonstrated that the major component among the volatile products is monomeric vinyl chloride and that the process causes deposition of Cl-containing polymeric films. The proportion between the volatile and solid products as well as the nature of the deposited films at different laser fluences have been examined. We show that the deposited films incorporate less Cl atoms than poly(vinyl chloride) and that they initially contain conjugated CC bonds and incorporate nano-sized fibre and necklace features. The process represents the first example of thermal degradation of poly(vinyl chloride) into monomer and makes it possible to fabricate crosslinked Cl-containing intractable polymer films.     

Functionalization and Rearrangement of Spirocyclohexadienyl Oxindoles: Experimental and Theoretical Investigations

The preparation and functionalization of spirocyclohexa‐2,5‐diene oxindoles is described. The spirocyclic core of the title compounds was installed by using a SmI₂‐mediated cyclization of aryl iodobenzamides. Epoxidation with CF₃CO₃H was then carried out and was shown to occur with a high level of diastereocontrol: the reagent approaches the diene moiety syn to the amide group, which is likely to be as a consequence of hydrogen bonding between the amide C?O bond and the peracid hydrogen. Carbanionic functionalization of the spirocyclohexa‐2,5‐diene oxindoles was then examined, leading to an unprecedented rearrangement of the strained spiro system into dearomatized phenanthridinones. Upon treatment with lithium diisopropylamide (LDA) at ?40 °C, the dienes rearranged to provide a phenanthridinone lithium enolate intermediate that was trapped by electrophiles including alkyl halides and aldehydes. Interestingly, alkylation and hydroxyalkylation occurred with different regiocontrol. DFT calculations were performed that rationalize the observed skeleton rearrangement, emphasizing the role of LDA/diisopropylamine in this rearrangement. The proposed mechanism thus relies on a thermodynamically driven diisopropylamine‐mediated proton transfer with the cleavage of the diene–amide C?O bond as the key step.     

The Synthesis and Reactions of Yomogi Alcohol. Conversion of the artemisyl skeleton to the santolinyl skeleton by a 1,2-shift of a vinyl group. Synthesis of santolinatriene

The synthesis of yomogi alcohol (2, 5, 5-trimethylhepta-3,6-dien-2-ol, 2 ) is described, and experiments directed towards its allylic rearrangement to artemisia alcohol detervatives have been carried out. Acidic reagents open the ring of yomogi alcohol epoxide ( 16 ) at with participation of the 6,7-double-bond, a shift of the vinyl group results to yield a compound with the santolinyl skeleton. The same reagents are without effect when this double bond reduced. Action of butyllithium of the benzaldehyde acetal ( 41 ) of 2, 5-dimethyl-4-vinyl-2, dihydroxy-hex-5-ene ( 28 ), obtained by acid-catalyzed ring opening of yomogi alcohol epoxide in the presence of benzaldehyde, leads to santolinatriene ( 42 ). This vinyl shift is not observed in the case of O-acetyl yomogi alcohol epoxide ( 46 ), from white a compound believed to be an oxetan 48 (R ? COCH₃) is formed with concomitent shift of the acetate group. Further unusual reactions of the oxetan are described, and some observation about the epoxidation of sterically hindered allyl alcohols and their acetates are made.     

Preparation of [5,6]- and [6,6]-oxahomofullerene derivatives and their interconversion by Lewis acid assisted reactions of fullerene mixed peroxides

[60]Fullerene mixed peroxides C60(O)(OOtBu)4 exhibit chemo- and regioselective reactions under mild conditions. The epoxy moiety is opened by ferric chloride to form vicinal hydroxy chloride C60Cl(OH)(OOtBu)4. BF3 is also effective in opening the epoxy moiety. The O-O bond of the fullerene mixed peroxide is cleaved by aluminum chloride to form both [5,6]- and [6,6]-fullerene hemiketals (oxohomo[60]fullerenes). A Hock-type rearrangement is proposed for the formation of the hemiketals, in which a fullerene C-C bond is cleaved. Lewis acids and/or visible light can initiate isomerization of the hemiketal isomers. Single-crystal X-ray analysis and theoretical calculations confirmed the results.     

α‐Halogenoacetanilides as Hydrogen‐Bonding Organocatalysts that Activate Carbonyl Bonds: Fluorine versus Chlorine and Bromine

α‐Halogenoacetanilides (X=F, Cl, Br) were examined as H‐bonding organocatalysts designed for the double activation of C?O bonds through NH and CH donor groups. Depending on the halide substituents, the double H‐bond involved a nonconventional C?H???O interaction with either a H?CX_n (n=1–2, X=Cl, Br) or a H?C_Ar bond (X=F), as shown in the solid‐state crystal structures and by molecular modeling. In addition, the catalytic properties of α‐halogenoacetanilides were evaluated in the ring‐opening polymerization of lactide, in the presence of a tertiary amine as cocatalyst. The α‐dichloro‐ and α‐dibromoacetanilides containing electron‐deficient aromatic groups afforded the most attractive double H‐bonding properties towards C?O bonds, with a N?H???O???H?CX₂ interaction.     

On the Catalytic Mechanism of (S)‐2‐Hydroxypropylphosphonic Acid Epoxidase (HppE): A Hybrid DFT Study

The mechanism of oxidative epoxidation catalyzed by HppE, which is the ultimate step in the biosynthesis of fosfomycin, was studied by using hybrid DFT quantum chemistry methods. An active site model used in the computations was based on the available crystal structure for the HppE‐Fe^II‐(S)‐HPP complex and it comprised first‐shell ligands of iron as well as second‐shell polar groups interacting with the substrates. The reaction energy profiles were constructed for three a priori plausible mechanisms proposed in the literature, and it was found that the most likely scenario for the native substrate, that is, (S)‐HPP, involves generation of the reactive Fe^III? O ^. /Fe^IV?O species, which is responsible for the C? H bond‐cleavage. At the subsequent reaction stage, the OH‐rebound, which would lead to a hydroxylated product, is prevented by a fast protonation of the OH ligand and, as a result, ring closure is the energetically preferred step. For the R enantiomer of the substrate ((R)‐HPP), which is oxidized to a keto product, comparable barrier heights were found for the C? H bond activation by both the Fe^III? O₂ ^. and Fe^IV?O species.     

Acid-Catalyzed Hydration of anti-Sesquinorbornene

The acid-catalyzed hydration of anti-sesquinorbornene (1) has been studied at 25 degrees C in 20% DME/H(2)O from 0.001 M < [HC1] < 0.05 M. The second-order rate constant for hydration is 5.35 +/- 0.07 M(-)(1) s(-)(1) which can be compared with a value of 1.38 +/- 0.06 M(-)(1) s(-)(1) for ethyl vinyl ether determined under the same conditions. The solvent deuterium kinetic isotope effect for hydration of 1 is 2.7, and a plot of the observed second-order rate constant for the hydration in a mixed solvent system of H(2)O/D(2)O against the atom fraction of deuterium (n) is bowed upward. The reaction also shows marked buffer catalysis by formic, chloroacetic, and dichloroacetic acids, the Br?nsted alpha being 1 for these three carboxylic acids: H(3)O(+) does not fit on this Br?nsted line. A mechanism for the reaction is presented which is consistent with the generally accepted one for acid-catalyzed hydration of an alkene in which the rate-limiting step involves proton transfer from H(3)O(+) to the double bond. Whether attack of a second water on the developing carbocation occurs simultaneously with protonation cannot be ascertained from the data for 1, but if so, the extent of its C-OH(2) bond formation must be small enough that there is little change in the bonding of these O-H bonds.     

Regio- and endo-selective

Irradiation of various meta- and para-substituted homobenzoquinones with ethyl vinyl ether gave the [2 + 2] photoadducts, tricyclic diones, regio- and endo-selectively and in good yields. The tricyclic skeleton has an anti-form built by the addition of ethyl vinyl ether from the less hindered side of homoquinones. All of the CH(3), Cl, Br, and CH(3)O substituents at the reacting C=C double bond afforded head-to-head (HH) addition predominantly. In the case of CH(3), Cl, and Br, the ethoxy group was oriented in the endo-position, while the CH(3)O substituent led to a 1/5 mixture with the exo-isomer. It was also found that the Br-substituted [2 + 2] adducts undergo a facile skeletal rearrangement, being converted into dihydro-o-benzoquinone monomethide derivatives for para-substitution and dihydrobenzofuran derivatives for meta-substitution, probably under the influence of the in situ generated HBr. Intramolecular [2 + 2] photocycloaddition of an alkenylhomobenzoquinone afforded a tetracyclic dione.     

Photochemische Reaktionen. 71. Mitteilung. Die Photoisomerisierung eines spirocyclischen α, β-Epoxyketons

On direct UV. irradiation and on triplet sensitization with acetophenone the spirocyclic epoxyketone (R)-(?)- 9 undergoes racemization (Φ^313/334 0.014, Φ^Sens 0.0060) and rearrangement to the enantiomeric spiro-β-diketones (R)-(+)- 14 (Φ^313/334 0.068, Φ^Sens 0.0037) and (S)-(?)- 14 (Φ^313/334 0.024, Φ^Sens 0.0023). The quantum yield data show that triplet reaction due to intersystem crossing is unimportant on direct irradiation, and they exclude that one common diradical intermediate of type d (Scheme 8) for the three reaction paths is involved in both the singlet and the triplet reaction. The postulate of photolytic Cα? O epoxide cleavage to intermediates of type d for the rearrangement requires that the rate of rearrangement is greater than the rate of rotation around the Cα? Cβ; bond in a given d , and that the rate difference is greater in singlet-generated d than in the triplet analogue. Reclosure of diradicals d and/or photolytic Cα? Cβ cleavage to diradical e and reclosure can account for the racemization of 9 . The optically active spiro-β-diketone 14 was found to racemize also on direct irradiation and on triplet sensitization. Furthermore, both 14 and the isomeric β-diketone 20 , which was obtained by UV. irradiation of the homocyclic epoxyketone 19 , photochemically isomerize to the enol lactones 23 and 21 , respectively.     

2,8‐Di­hydroxy‐1,3,7,9‐tetra­methyl‐6,12‐di­hydro­dipyrido­[1,2‐a:1′,2′‐d]pyrazine­diyl­ium dichloride dihydrate

The 2,8‐di­hydroxy‐1,3,7,9‐tetra­methyl‐6,12‐di­hydro­di­pyrido[1,2‐a:1′,2′‐d]pyrazine­diyl­ium dication possesses 2/m symmetry and lies in the mirror plane together with a chloride anion and the water O atom. The dication also lies on an inversion centre, i.e. C₁₆H₂₀N₂O₂²⁺·2Cl^?·2H₂O. Due to these symmetry constrictions the dication adopts an unexpected planar conformation. Molecules are linked by O—H?O and O—H?Cl hydrogen bonds to form chains, which are cross‐connected by C—H?Cl attractive interactions forming a complex three‐dimensional hydrogen‐bond network.