Evaluation of 1‐arylpiperazine derivative of hydroxybenzamides as 5‐HT1A and 5‐HT7 serotonin receptor ligands: An experimental and molecular modeling approach

The synthesis and evaluation as 5‐HT_1A and 5‐HT₇ serotonin receptor ligands of the two sets of O‐substituted hydroxybenzamides, structurally related to 2‐{3‐[4‐(2‐methoxyphenyl)piperazin‐1‐yl]propoxy}benzamide ( 1 ), (K_i 5‐HT_1A = 21 nM, 5‐HT₇ = 234 nM) are reported. To affect the affinity for 5‐HT_1A and 5‐HT₇ receptors, an amide moiety ( 2 , 3 , 4 , 5 , 6 ) and a hydrocarbon chain length ( 7 , 8 , 9 , 10 ) were modified. The serotonergic activity of compounds 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 was generally higher in the case of 5‐HT_1A receptors compared with 5‐HT₇ ones; the most active 5‐HT_1A ligands being meta‐isomer 2 (K_i = 7 nM) and both analogs of 1 with the longest spacer, i.e., penta‐ and hexa‐methylene derivatives 9 and 10 (K_i = 4 and 3 nM, respectively). The observed biological properties of compounds 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 were elucidated using molecular modeling procedures. J. Heterocyclic Chem., (2010).     

Synthesis and biological testing of 3‐phenyloctahydro‐pyrimido[1,2‐a]‐s‐triazine derivatives

A series of 46 3‐phenyloctahydropyrimido[1,2‐a]‐s–triazine derivatives were synthesized. This synthesis was performed via iminodimethylation of dialkylated 2‐aminopyrimidinedione synthons by substituted primary arylamines. In vitro pharmacological evaluation of these compounds is reported. One of them exhibited antifungal activity against Microsporum canis (10^?6₅₀10^?5 mol/L), and another showed affinity for serotoninergic 5‐HT_1A and 5‐HT_2b receptors (10^?8₅₀10^?7 mol/L).     

The synthesis of cyclic and acyclic long‐chain arylpiperazine derivatives of salicylamide as serotonin receptor ligands

The 1‐arylpiperazine series of N‐substituted 1,3‐benzoxazine‐2,4‐diones as well as O‐ and N‐substituted salicylamides with an n‐propyl chain were synthesized in order to explore the effect of cyclic and acyclic salicylamide moieties on their binding affinity for 5‐HT_1A, 5‐HT_2A and 5‐HT₇ receptor sites. Target compounds 1 and 2 were prepared by a two‐step procedure, i.e. by alkylation of 1,3‐benzoxazine‐2,4‐dione or salicylamide with 1,3‐dibromopropane and next by condensation of 3‐bromopropyl intermediates with arylpiperazines; syntheses of 3‐bromopropyl intermediates were performed in solvent‐free conditions. Compounds 3 were prepared by hydrolysis of 1 . In respect of salicylamide moieties, binding affinities for 5‐HT_1A and 5‐HT₇ receptors increase according to the rank of derivatives 3 < 1 < 2 , for the same arylpiperazines. Regarding 5‐HT_2A receptors, increased activity of ligands was changed in reverse order to the affinity for 5‐HT_1A, i.e. 2 < 1 < 3 . 5‐HT_1A and 5‐HT₇ receptor binding constants were the highest for the 2‐methoxyphenyl ligand 2c , while the 3‐chlorophenyl ligand 3b was most active for 5‐HT_2A receptors.     

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 .     

Synthesis of Some Aminophosphonates Bearing N‐(Fluorophenyl)‐piperazynyl Moiety and Their Activity toward Serotonin Receptors

Syntheses of a series of compounds bearing a 1‐(fluorophenyl)piperazin‐4‐ylmethyl moiety, namely dialkyl 1‐(fluorophenyl)piperazin‐4‐ylmethyl phosphonates 3a–f , diethyl 2‐[1‐(fluorophenyl)piperazin‐4‐yl]‐ethyl phosphonates 4a,b , diethyl 3‐[1‐(4‐fluorophenyl)‐piperazin‐4‐yl]‐propyl phosphonate 5 , and di[1‐(fluorophenyl)piperazin‐4‐yl]methanes 6a,b were performed, and some of them were screened for their affinity for serotonin 5‐HT_1A, 5‐HT₆, and 5‐HT₇ receptors. Moderate interactions with these receptors were demonstrated.     

The Photocyclodimers of 2,3‐Dihydro‐2,2‐dimethyl‐4H‐pyran‐4‐one

On irradiation (350 nm) in benzene solution, dihydropyranone 3 affords predominantly (75%) the cis‐anti‐cis HH‐dimer 4 , but in smaller amounts (12%) also dimer 5 , wherein one of the six‐membered rings is trans‐fused to the (central) cyclobutane ring. The constitution and configuration of 5 was fully elucidated by NMR‐analysis. On contact with SiO₂, 5 isomerizes quantitatively to the cis‐anti‐cis HT‐dimer 7 , the structure of which was established by X‐ray crystal‐structure determination.     

Coordination Polymer Flexibility Leads to Polymorphism and Enables a Crystalline Solid–Vapour Reaction: A Multi‐technique Mechanistic Study

Despite an absence of conventional porosity, the 1D coordination polymer [Ag₄(O₂C(CF₂)₂CF₃)₄(TMP)₃] ( 1 ; TMP=tetramethylpyrazine) can absorb small alcohols from the vapour phase, which insert into Ag?O bonds to yield coordination polymers [Ag₄(O₂C(CF₂)₂CF₃)₄(TMP)₃(ROH)₂] ( 1‐ROH ; R=Me, Et, iPr). The reactions are reversible single‐crystal‐to‐single‐crystal transformations. Vapour‐solid equilibria have been examined by gas‐phase IR spectroscopy (K=5.68(9)×10^?5 (MeOH), 9.5(3)×10^?6 (EtOH), 6.14(5)×10^?5 (iPrOH) at 295 K, 1 bar). Thermal analyses (TGA, DSC) have enabled quantitative comparison of two‐step reactions 1‐ROH → 1 → 2 , in which 2 is the 2D coordination polymer [Ag₄(O₂C(CF₂)₂CF₃)₄(TMP)₂] formed by loss of TMP ligands exclusively from singly‐bridging sites. Four polymorphic forms of 1 ( 1‐A^LT , 1‐A^HT , 1‐B^LT and 1‐B^HT ; HT=high temperature, LT=low temperature) have been identified crystallographically. In situ powder X‐ray diffraction (PXRD) studies of the 1‐ROH → 1 → 2 transformations indicate the role of the HT polymorphs in these reactions. The structural relationship between polymorphs, involving changes in conformation of perfluoroalkyl chains and a change in orientation of entire polymers (A versus B forms), suggests a mechanism for the observed reactions and a pathway for guest transport within the fluorous layers. Consistent with this pathway, optical microscopy and AFM studies on single crystals of 1‐MeOH / 1‐A^HT show that cracks parallel to the layers of interdigitated perfluoroalkyl chains develop during the MeOH release/uptake process.     

Dimensional Control of Block Copolymer Nanofibers with a π‐Conjugated Core: Crystallization‐Driven Solution Self‐Assembly of Amphiphilic Poly(3‐hexylthiophene)‐b‐poly(2‐vinylpyridine)

With the aim of accessing colloidally stable, fiberlike, π‐conjugated nanostructures of controlled length, we have studied the solution self‐assembly of two asymmetric crystalline–coil, regioregular poly(3‐hexylthiophene)‐b‐poly(2‐vinylpyridine) (P3HT‐b‐P2VP) diblock copolymers, P3HT₂₃‐b‐P2VP₁₁₅ (block ratio=1:5) and P3HT₄₄‐b‐P2VP₁₁₅ (block ratio=ca. 1:3). The self‐assembly studies were performed under a variety of solvent conditions that were selective for the P2VP block. The block copolymers were prepared by using Cu‐catalyzed azide–alkyne cycloaddition reactions of azide‐terminated P2VP and alkyne end‐functionalized P3HT homopolymers. When the block copolymers were self‐assembled in a solution of a 50 % (v/v) mixture of THF (a good solvent for both blocks) and an alcohol (a selective solvent for the P2VP block) by means of the slow evaporation of the common solvent; fiberlike micelles with a P3HT core and a P2VP corona were observed by transmission electron microscopy (TEM). The average lengths of the micelles were found to increase as the length of the hydrocarbon chain increased in the P2VP‐selective alcoholic solvent (MeOH<iPrOH<nBuOH). Very long (>3 μm) fiberlike micelles were prepared by the dialysis of solutions of the block copolymers in THF against iPrOH. Furthermore the widths of the fibers were dependent on the degree of polymerization of the chain‐extended P3HT blocks. The crystallinity and π‐conjugated nature of the P3HT core in the fiberlike micelles was confirmed by a combination of UV/Vis spectroscopy, photoluminescence (PL) measurements, and wide‐angle X‐ray scattering (WAXS). Intense sonication (iPrOH, 1 h, 0 °C) of the fiberlike micelles formed by P3HT₂₃‐b‐P2VP₁₁₅ resulted in small (ca. 25 nm long) stublike fragments that were subsequently used as initiators in seeded growth experiments. Addition of P3HT₂₃‐b‐P2VP₁₁₅ unimers to the seeds allowed the preparation of fiberlike micelles with narrow length distributions (L_w/L_n <1.11) and lengths from about 100‐300 nm, that were dependent on the unimer‐to‐seed micelle ratio.     

Methyl 2‐acetamido‐2‐deoxy‐β‐d‐glucopyranoside dihydrate and methyl 2‐formamido‐2‐deoxy‐β‐d‐glucopyranoside

Methyl 2‐acetamido‐2‐deoxy‐β‐d ‐glucopyranoside (β‐GlcNAcOCH₃), (I), crystallizes from water as a dihydrate, C₉H₁₇NO₆·H₂O, containing two independent molecules [denoted (IA) and (IB)] in the asymmetric unit, whereas the crystal structure of methyl 2‐formamido‐2‐deoxy‐β‐d ‐glucopyranoside (β‐GlcNFmOCH₃), (II), C₈H₁₅NO₆, also obtained from water, is devoid of solvent water molecules. The two molecules of (I) assume distorted ⁴C₁ chair conformations. Values of ϕ for (IA) and (IB) indicate ring distortions towards B_C2,C5 and ^C3,O5B, respectively. By comparison, (II) shows considerably more ring distortion than molecules (IA) and (IB), despite the less bulky N‐acyl side chain. Distortion towards B_C2,C5 was observed for (II), similar to the findings for (IA). The amide bond conformation in each of (IA), (IB) and (II) is trans, and the conformation about the C—N bond is anti (C—H is approximately anti to N—H), although the conformation about the latter bond within this group varies by ∼16°. The conformation of the exocyclic hydroxymethyl group was found to be gt in each of (IA), (IB) and (II). Comparison of the X‐ray structures of (I) and (II) with those of other GlcNAc mono‐ and disaccharides shows that GlcNAc aldohexopyranosyl rings can be distorted over a wide range of geometries in the solid state.     

Finding all‐nonmetal transition‐metal‐like superatom and its magnetic building block

In novel superatom chemistry, it is very attractive that all‐metal clusters can mimic the behaviors of nonmetal atoms and simple nonmetal molecules. Wizardly all‐metal halogen‐like superatom Al₁₃ with 2P⁵ sub shell (corresponding to the 3p⁵ of chlorine) is the most typical example. In contrast, how to mimic the behaviors of magnetic transition‐metal atom using all‐nonmetal cluster is an intriguing challenge for superatom chemistry. In response to this based on human intuition, using quantum chemistry methods and extending jellium model from metal cluster to all‐nonmetal cluster, we have found out that all‐nonmetal octahedral B₆ cluster with characteristic jellium electron configuration 1S²1P⁶2S²1D⁸ in the triplet ground state can mimic the behaviors of transition‐metal Ni atom with electron configuration 3s²3p⁶4s²3d⁸ in electronic configuration, physics and chemistry. Interestingly, the characteristic order of 1S1P2S1D for the B₆ nonmetal cluster with short B‐B lengths is different from that of the traditional jellium model—1S1P1D2S for metal clusters with long M‐M lengths, which exhibits a novel size effect of nonmetal cluster on jellium orbital ordering. Based on the jellium electron configuration, the B₆ with the spin moment value of 2μ_B is a new all‐nonmetal transition‐metal nickel‐like superatom exhibiting a new kind of all‐nonmetal magnetic superatom. Finding the application of the all‐nonmetal magnetic superatom, we encapsulate the magnetic superatom B₆ inside fully hydrogenated fullerene forming a clathrate B₆@C₆₀H₆₀ with the spin moment value of 2μ_B. As the C₆₀H₆₀ cage as a polymerization unit can conserve the spin moment of endohedral B₆, the clathrate B₆@C₆₀H₆₀ is a new all‐nonmetal magnetic superatom building block. Naturally, magnetic superatom structures of the B₆ and B₆@C₆₀H₆₀ may be metastable.     

Ten‐vertex rhodadithiaborane ­chemistry: [8‐{I(CH2)5}‐3‐(η5‐C5Me5)‐arachno‐3,7,8‐RhS2B8H9]

Neutral 8‐(5‐iodo‐n‐pentyl)‐3‐(η⁵‐penta­methyl­cyclo­pentadi­enyl)‐arachno‐3‐rhoda‐7,8‐di­thia­undecaborane, [Rh(C₅H₁₉B₈­IS₂)­(C₁₀H₁₅)], obtained from the [arachno‐7,8‐S₂B₉H₁₀]^? anion by treatment with I(CH₂)₅I followed by [Rh(C₅Me₅)Cl₂]₂ and N,N,N′,N′‐tetra­methyl‐1,8‐di­amino­naphthalene, has the 11‐vertex cluster geometry of [arachno‐7,8‐S₂B₉H₁₀]^?, but with an {Rh(C₅Me₅)} unit in the 3‐position instead of a {BH} unit, and with a –(CH₂)₅I chain attached exo to an S atom.     

How to Make 8,1,2‐closo‐MC2B9 Metallacarboranes

Three examples of the rare 8,1,2‐closo‐MC₂B₉ isomeric form of an icosahedral metallacarborane have been isolated as unexpected trace products in reactions. Seeking to understand how these were formed we considered both the nature of the reactions that were being undertaken and the nature of the coproducts. This led us to propose a mechanism for the formation of the 8,1,2‐closo‐MC₂B₉ species. The mechanism was then tested, leading to the first deliberate synthesis of an example of this isomer. Thus, deboronation of 4‐(η‐C₅H₅)‐4,1,8‐closo‐CoC₂B₁₀H₁₂ selectively removes the B5 vertex to yield the dianion [nido‐(η‐C₅H₅)CoC₂B₉H₁₁]^2?, oxidative closure of which affords 8‐(η‐C₅H₅)‐8,1,2‐closo‐CoC₂B₉H₁₁ in moderate yield.     

Electrophile‐Induced Nucleophilic Substitution of the nido‐Dicarbaundecaborate Anion nido‐7,8‐C2B9H12− by Conjugated Heterodienes

Substitution of the dicarbaundecaborate anion nido‐7,8‐C₂B₉H₁₂^? ( 1 ) by precise hydride abstraction followed by nucleophilic attack usually leads to symmetric products 10‐R‐nido‐7,8‐C₂B₉H₁₁. However, thioacetamide (MeC(S)NH₂) as nucleophile and acetone/AlCl₃ as hydride abstractor gave asymmetric 9‐[MeC(NHiPr)S]‐nido‐7,8‐C₂B₉H₁₁ ( 2 ), whereas N,N‐dimethylthioacetamide (MeC(S)NMe₂) gave the expected symmetric 10‐[MeC(NMe₂)S]‐nido‐7,8‐C₂B₉H₁₁ ( 4 ). For the formation of 2 , acetone and thioacetamide are assumed to give the intermediate MeC(S)N(CMe₂) ( 3 ), which then attacks 1 with formation of 2 . Similarly, reaction of acetyliminium chloride [MeC(O)NH(CPh₂)]Cl ( 5 ) with 1 in THF gave a mixture of 9‐ and 10‐substituted [MeC(NHCHPh₂)O]‐nido‐7,8‐C₂B₉H₁₁ ( 6 and 7 , respectively). These reactions are the first examples in which compounds (here heterodienes) that unite the functionalities of both hydride acceptor and nucleophilic site react with 1 in a bimolecular fashion. Furthermore, the analogous reaction of 1 and 5 (in an equilibrium mixture with acetyl chloride and benzophenone imine) in MeCN afforded 10‐[MeC(NCPh₂)NH]‐nido‐7,8‐C₂B₉H₁₁ ( 8 ) and MeC(O)NHCHPh₂ ( 9 ).     

Synthesis and biological properties of 1,8‐naphthalimidebutylamines. Serotonin 5‐HT1A and 5‐HT7 binding data and pass‐assisted search

Syntheses of the N‐substituted butyl derivatives of 1,8‐naphthalimide ( 1‐8 ), containing various arylpiperazines, tetrahydroisoquinoline and methylhomopiperazine moieties attached at 4‐position of the butyl chain have been described. Biological activities were evaluated in vitro for their ability to bind to serotonin 5‐HT_1A and 5‐HT₇ receptors. Due to the structural similarity of derivatives 1‐8 to psychotropic agents, the pharmacological properties of target compounds were predicted using PASS program.     

[1,1,2,2‐(CO)4‐1,2‐μ‐(CO)‐4,11‐(SMe2)2‐closo‐1,2‐Co2B10H8]

The title compound, 1,1,2,2‐tetra­carbonyl‐1,2‐μ‐carbonyl‐4,11‐di­methyl­sulfido‐closo‐1,2‐dicobaltadodecaborane, [Co₂(C₄H₂₀B₁₀S₂)(CO)₅], has a closo 12‐vertex {1,2‐Co₂B₁₀H₈} structure with SMe₂ ligands at the exo‐4‐ and 11‐positions. The cluster displays close structural similarities to the SEt₂ analogue.     

η5‐(3)‐1‐Methyl‐1,2‐dicarbollyl‐η5‐2′,5′‐dimethylpyrrolylcobalt(III)

In the title compound, (η⁵‐2,5‐di­methyl­pyrrolyl)[(7,8,9,10,11‐η)‐7‐methyl‐7,8‐dicarba‐nido‐undecaborato]­cobalt(III), [3‐Co{η⁵‐[2,5‐(CH₃)₂‐NC₄H₂]}‐1‐CH₃‐1,2‐C₂B₉H₁₀] or [Co(C₃H₁₃B₉)(C₆H₈N)], the Co^III atom is sandwiched between the pentagonal faces of the pyrrolyl and dicarbollide ligands, resulting in a neutral mol­ecule. The C—C distance in the dicarbollide cage is 1.649 (3) Å.     

Bridging gold: B‐Au‐B three‐center‐two‐electron bonds in electron‐deficient B2Aun−/0 (n = 1, 3, 5) and mixed analogues

A systematic density functional theory and wave function theory investigation on the geometrical and electronic structures of the electron‐deficient diboron aurides B₂Au (n = 1, 3, 5) and their mixed analogues B₂H_mAu (m + n = 3, 5) has been performed in this work. Ab initio theoretical evidences strongly suggest that bridging gold atoms exist in the ground states of C_2v B₂Au^?(¹A₁), C₂ B₂Au(¹A), C_2v B₂Au₃(²B₁), C_2v B₂Au(¹A₁), and C_s B₂Au₅(²A″), which all prove to possess a B? Au? B three‐center‐two‐electron (3c‐2e) bond. For B₂H_mAu (m + n = 3, 5) mixed anions, bridging B? Au? B units appear to be favored in energy over bridging B? H? B, as demonstrated by the fact that the Au‐bridged C_2v B₂H₂Au^? (¹A₁), C_s B₂HAu (¹A′), and C₁ B₂HAu (¹A) lie clearly lower than their H‐bridged counterparts C_s B₂H₂Au^? (¹A′), C₂ B₂HAu (¹A), and C_2v B₂HAu (¹A₁), respectively. Orbital analyses indicate that Au 6s makes about 92–96% contribution to the Au‐based orbitals in these B‐Au‐B 3c‐2e interactions, whereas Au 5d contributes 8–4%. The adiabatic and vertical detachment energies of the concerned anions have been calculated to facilitate their future experimental characterizations. The results obtained in this work establish an interesting 3c‐2e bonding model (B? Au? B) for electron‐deficient systems in which Au 6s plays a major role with non‐negligible contribution from Au 5d. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2011     

Unveiling 79‐Year‐Old Ixene and Its BN‐Doped Derivative

Polycyclic aromatic hydrocarbons (PAHs) are key components of organic electronics. The electronic properties of these carbon‐rich materials can be controlled through doping with heteroatoms such as B and N, however, few convenient syntheses of BN‐doped PAHs have been reported. Described herein is the rationally designed, two‐step syntheses of previously unknown ixene and BN‐doped ixene (B₂N₂‐ixene), and their characterizations. Compared to ixene, B₂N₂‐ixene absorbs longer‐wavelength light and has a smaller electrochemical energy gap. In addition to its single‐crystal structure, scanning tunneling microscopy revealed that B₂N₂‐ixene adopts a nonplanar geometry on a Au(111) surface. The experimentally obtained electronic structure of B₂N₂‐ixene and the effect of BN‐doping were confirmed by DFT calculations. This synthesis enables the efficient and convenient construction of BN‐doped systems with extended π‐conjugation that can be used in versatile organic electronics applications.     

The dimeric mixed‐ligand titana­carborane sandwich [1‐(Cp)‐1‐Ti‐2‐(Me)‐3‐(SiMe3)‐2,3‐C2B4H4]2

The title dimer, bis­[1‐cyclo­penta­dienyl‐2‐methyl‐1‐titana‐3‐tri­methylsilyl‐2,3‐dicarba‐closo‐hexaborane(6)], [Ti(C₅H₅)(C₆­H₁₆­B₄Si)]₂, reveals that the centrosymmetric mol­ecule consists of two bent‐sandwich titanacarboranes bridged by the B—H—Ti bonds. The average bond distances are Ti—B 2.445 (3), Ti—C(cage) 2.334 (2) and Ti—C(Cp) 2.376 (3) Å, and the corresponding bond angles are Cp—Ti—Cp 163.2 (1) and Cp—Ti—Cb (Cb = C₂B₃ face) 139.9 (1)°; the Ti—H separations are 2.10 (2) and 2.19 (2) Å.     

Synthesis of A2B6‐Type [36]Octaphyrins: Copper(II)‐Metalation‐Induced Fragmentation Reactions to Porphyrins and N‐Fusion Reactions of meso‐(3‐Thienyl) Substituents

5,10,15‐Tris(pentafluorophenyl)tetrapyrromethane was efficiently prepared through a route involving stepwise diaroylation of 5‐pentafluorophenyldipyrromethane. A₂B₆‐type [36]octaphyrins were prepared by the cross condensation of the tetrapyrromethane with aryl aldehydes in moderate yields. A₂B₆‐type [36]octaphyrins bearing 2,4,6‐trifluorophenyl, 2,6‐dichlorophenyl, and phenyl substituents underwent Cu^II‐metalation‐induced fragmentation to give two molecules of AB₃‐type Cu^II porphyrins. A₂B₆‐type [36]octaphyrin bearing 3‐thienyl substituents underwent thermal N‐thienyl fusion reactions to provide a modestly aromatic [38]octaphyrin, which, upon treatment with MnO₂, underwent further N‐thienyl fusion and subsequent oxidation to give a nonaromatic doubly N‐thienyl fused [36]octaphyrin.