Pyridiniums as potential synthetic substitutes for nitrogen mustards

Dialkylamino-alkyl primary amines 1b and 2b are converted by pyrylium salts into the corresponding pyridinium derivatives. The pyridinium salts act as aminoalkylating agents for representative O-, S-, N-, and C-nucleophiles and are potentially safe substitutes for nitrogen mustards in the reactions.     

Some reactions of 4H-pyrylium salts with tributylphosphine and with tertiary amines

The phosphonium salt from tributylphosphine and 2,6-di(4-methoxyphenyl)pyrylium perchlorate (3) reacted with diisopropylethylamine in acetonitrile to give 2,2′,6,6′-tetra(4-methoxyphenyl)-Δ^4.4′-bi-4H-pyran in quantitative yield. The reaction of 3 and other 4H-pyrylium salts with tertiary amines gave 4H-pyrans.     

Verallgemeinerung der Aminopentadienal‐Umlagerung

Generalization of the Aminopentadienal Rearrangement Contrary to the rearrangement of 3‐amino‐3‐X‐prop‐2‐enals 2 (R=H), which easily give 3‐X‐prop‐2‐enamides 3 at low temperature, the postulated rearrangement (Scheme 1) of the vinylogous 5‐amino‐5‐X‐penta‐2,4‐dienals 6 (R=H) normally stops at the level of 2‐aminopyrylium salts 7 . The main reason is that the charge in salts of type 7 is highly delocalized, leading to low‐energy species, which make addition of weak nucleophiles difficult. In this paper, two concepts for increasing the chances of the `aminopentadienal rearrangement' 6 →→ 8 are presented and substantiated by typical experiments. On one side, the easily available 2‐aminopyrylium chlorides 7 (X=Cl) are reacted with a twofold excess of secondary amines (Scheme 2) to give 5‐(dialkylamino)penta‐2,4‐dienamides of type 9 and 10 . On the other hand, after replacing the amino groups of 6 by PhO and EtO groups, the corresponding 5‐chloro‐5‐phenoxy‐ ( 13b ) and 5‐chloro‐5‐ethoxypenta‐2,4‐dienals ( 13a ) easily rearrange at low temperature to give 5‐chloropenta‐2,4‐diene‐1‐carboxylates 18a and 18b , respectively, which are now obviously lower in energy than the corresponding pyrylium‐salt intermediates 16 (Scheme 4).     

Synthesis and Reactions of 1-(3-Chloropropyl)-6,7-dimethoxy-3-methylbenzo[c]pyrylium Perchlorate

Acid-catalyzed acylation of 3,4-dimethoxyphenylacetone with -chlorobutyryl chloride gave 1-(3-chloropropyl)-6,7-dimethoxy-3-methylbenzo[c]pyrylium perchlorate. Recyclization of the product with nitrogen nucleophiles (ammonia, primary amines, hydrazine derivatives, hydroxylamine) led through the corresponding isoquinolinium salts to benzo[f]indolizinium, pyridazino[2,1-b]isoquinolinium, and 1,2-oxazino[2,1-b]isoquinolinium salts.     

Pyrylium Mediated Transformations of Primary Amino Groups into Other Functional Groups. New Synthetic Methods (41)

The first pyrylium salt was isolated some 80 years ago, yet up to the 1950s only moderate interest was taken in the preparation, properties and uses of such salts. However, the past thirty years has seen a phenomenal growth in the literature pertinent to this area of chemistry: the importance of pyrylium salts as intermediates has been realized. They are readily prepared by a variety of generally applicable routes, and they are highly reactive towards nucleophiles. Together, this enables the convenient synthesis of a great variety of acyclic and heterocyclic compounds. We have used highly substituted pyrylium salts for the two-step conversion of the amino group in alkylamines RNH₂ into numerous other functionalities. In the first step, the pyrylium salts are converted with the amines into N-substituted pyridinium salts, which, in the second step, react with Nu^? to give the desired products RNu. In some cases the R moiety is also changed, e.g. by elimination. Studies of the reactions of these pyridinium salts have allowed interesting insights into the mechanisms of nucleophilic substitution, in addition to rendering aliphatic amines important synthetic intermediates. Thus, the method complements the diazotization procedure for the transformation of arylamines.     

The preparation of 4-substituted pyrylium salts and their use in dienal synthesis

The unsubstituted pyrylium nucleus is shown to undergo reaction with cuprate or secondary Grignard organometallic reagents to give intermediate 4-substituted pyrans which are converted into the corresponding 4-substituted pyrylium salts (7 examples) in fair to good overall yield. The synthetic utility of the 4-substituted pyrylium heterocycles is demonstrated by their reaction with organolithium reagents to give 3,5-disubstituted dienals in a highly stereospecific manner (7 examples) via electrocyclic ring opening of the intermediate 2-substituted pyrans.     

Ring transformations of heterocyclic compounds. XVI. Spiro[cyclohexadiene-dihydroacridines]. A novel class of spirodihydroacridines by ring transformation of pyrylium salts with 9-methylacridine and its quaternary salts

2,4,6-Triarylpyrylium salts 1 react with the in situ generated anhydrobase of 9,10-dimethylacridinium methosulfate ( 2a ) in the presence of anhydrous sodium acetate in ethanol by a 2,5-[C₄+C₂] pyrylium ring transformation to give the hitherto unknown 6-aroyl-3,5-diaryl-10′-methylspiro[cyclohexa-2,4-diene-1,9′-9′,10′-dihydro-acridines] 3 . When the pyrylium perchlorate 1a is treated under the same conditions with the N-ethyl, N-allyl or N-benzyl substituted acridinium salts 2b-d a dealkylation of these salts occurs and the N-unsubstituted spiro[cyclohexadiene-dihydroacridine] 4a is formed. The same compounds 4 can also be obtained by transformation of the pyrylium salts 1 with 9-methylacridine ( 7 ) and triefhylamine/acetic acid in ethanol. Structure elucidation is performed by an X-ray crystal structure determination of the spiro[cyclohexadiene-dihydroacridine] 3a . Spectroscopic data of the transformation products and their mode of formation are discussed.     

Reactions of pyrylium salts with nucleophilic agents

The reaction of -unsubstituted pyrylium salts with alkali-metal cyanides gives cyano- and carboxy-substituted pyrans and pyrylium salts, while the reaction with sodium sulfide gives dipyranyl sulfides. A phthalimide derivative of pyran is obtained from 2,6-diphenylpyrylium perchlorate and potassium phthalimide, while pyrylium cations react with zinc to give the corresponding dipyranyls.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1313–1316, October, 1972.     

On the condensation equilibrium in polymerization of caprolactam

The investigation of the condensation equilibrium of the hydrolytic polymerization is described for systems obtained by polymerizing caprolactam in the presence of water (or aminocaproic acid) and any of the following additives: mono- di-, and tricarboxylic acids, mono- and diamines, and the salts derived from a monoamine and either a mono- or dicarboxylic acid. Relationships in terms of the equilibrium constant K₂, the equilibrium conversion (K₃), and the initial composition were derived for the calculation of the molecular weights of the corresponding equilibrium polymers. Very good agreement between calculated and experimental data was observed. The results show that the thermodynamical quantities derived for the pure caprolactam–water system are also valid for polymerizations that involve the participation of organic acids, amines, and their salts in the initiation and equilibration.     

Chelating, bridging, and chain structures within Ag(I) and Cu(I) complexes of bis(nicotinyloxy), bis(isonicotinyloxy), and bis(pyrimidine-5-carboxyloxy)-1,8-disubstituted anthraquinone ligands

Reaction of Ag(I) and Cu(I) [M(NCCH₃)₄]X (X = BF₄⁻ and PF₆⁻) salts with 1,8-bis(nicotinyloxy)anthracene-9,10-dione (1), 1,8-bis(isonicotinyloxy)anthracene-9,10-dione (2), and 1,8-bis(pyrimidine-5-carboxyloxy)anthracene-9,10-dione (3), yield new chelating and bridging complexes and two new coordination polymers. The bridging capabilities of ligands 1 and 2 have not been demonstrated before, and ligand 1, by itself, has the flexibility to produce either chelated or bridged structures and an unusual ladder coordination polymer. The tetradentate ligand 3 also produces a one-dimensional coordination polymer in the presence of one equivalent of Ag(I). All complexes have been characterized by X-ray crystallography.     

Sels de pyrylium—XVII: Réactivité des sels de dialcoxy-2,4 pyrylium avec des agents nucléophiles. Formation et propriétés de sels d'amino-2 et de diamino-2,4 pyrylium; sels de dialcoxy-2,4 pyrylium,agents d'alcoylation

Secondary amines react with 2,4-dialcoxy 6-méthyl pyrylium salts to give two new series of 2-amino and 2,4-diamino pyrylium cations. 2,4-Dialkoxy pyrylium salts react as alkylating reagents. A comparison with 1,3-dialcoxy carbonium cations reactivity is reported.     

Ring transformations of heterocyclic compounds. XXI. Diastereoselective built‐up of an aroylcyclohexadiene moiety as second spiro‐connected ring at spiroindolines by pyrylium ring transformation

2,4,6‐Triarylpyrylium perchlorates 1 react with methyleneindolines 3 in situ generated from the corresponding methylindolium salts 2 , which are spiro‐fused with a cycloalkane, benzanellated cycloalkene or a heterocyclic system. These diastereoselective 2,5‐[C₄+C₂] pyrylium ring transformations are carried out in the presence of triethylamine/acetic acid in boiling ethanol to give the dispiroindolines 4 with a trans configuration of the more bulky substituents at the cyclohexadiene ring. By the same type of transformation the dispiro compounds 7/10 with an additional fused benzene ring are obtained from the pyrylium salt 1a and 6/9 , the benzo‐fused analogues of 3 . Spectroscopic data of the transformation products as well as their mode of formation are discussed.     

A versatile synthesis of benzothieno-annelated 1,2-dihydropyridine and 1,2,3,4-tetrahydropyridine derivatives: the effect of the structure of benzothieno-annelated pyridinium salts on their reduction by sodium borohydride

Abstract  

Benzothieno[2,3-c]pyridinium and benzothieno[2,3-c]quinolinium salts were synthesized either by quaternization of benzothieno[2,3-c]pyridines, or recyclization of benzothieno[2,3-c]pyrylium salts with primary amines. One-pot synthesis of benzothieno[3,2-g]indolizinium salts from 1-(3-chloropropyl)-benzothieno[2,3-c]pyrylium included consequent recyclization of the pyrylium core by ammonia into a pyridine intermediate and its further intramolecular quaternization reaction. Depending on the structure of benzothieno-annelated pyridinium salts, their reaction with sodium borohydride in methanol results in reduction of the pyridine core into tetrahydropyridine or dihydropyridine derivatives. Whereas reduction of benzothieno[2,3-c]pyridinium and benzothieno[3,2-g]indolizinium salts readily yields benzothieno-annelated tetrahydropyridines as a complex mixture of stereoisomers, reduction of benzothieno[2,3-c]quinolinium salts results in dihydropyridine derivatives. The structure of the latter, in particular, was confirmed by single-crystal X-ray diffraction analysis.     

Recyclization of 1,3-dimethylbenzo[b]furo[2,3-c]- and 1,3-dimethylbenzo[b]thieno[2,3-c]pyrylium when treated with secondary amines. Synthesis of 3-dialkylamino derivatives of dibenzofuran and dibenzothiophene

We have established that 2,4-dimethylbenzo[b]furo[3,2-c]pyrylium and 2,4-dimethylbenzo[b]thieno[3,2-c]pyrylium salts can undergo recyclization to 3-dialkylamino derivatives of dibenzofuran and dibenzothiophene when treated with secondary amines. We compare the physicochemical and spectral characteristics of the compounds obtained with the recyclization products of 1,3-dimethylbenzo[b]furo[2,3-c]- and 1,3-dimethylbenzo[b]thieno[2,3-c]pyrylium salts. L. M. Litvinenko Institute of Physical Organic Chemistry and Coal Chemistry, National Academy of Sciences of Ukraine, Donetsk 340114. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 182–185, February, 1998.     

The reactions of some pyraiiylideneiminium salts with amines. II

The iminium salt, N,N-dimethyl-N-[2-(2-phenyl-4H-l-benzopyran-4-ylidene)ethylidene] imin-ium perchlorate ( 3 ), reacts with secondary amines by exchanging the dimethylimino group for the added amine. Primary amines also reacted with 3 in the same manner. The bis iminium salts, N,N,N',N'-tetramethyl-N,N'-[2-(2-phenyl-4H-l-benzopyran-4-ylidene)-1,3-propanediylidene]-bis(immium perclilorate) ( 4 ) and the corresponding thiapyran derivative ( 5 ), react with ammonia to give 5-dimethylamino-2-phenyl-5H-1-benzopyrano[3,4-c]pyridine ( 10 ) and the thia analog 11 . The reactions of 4 and 5 with primary amines give 3-alkyl-5-dimethylamino-2-phenyl-5H-l-beiizopyrano[3,4-c]pyridinium perclilorate salts or the corresponding thiapyrano compounds. Compounds 4 and 5 react with secondary amines by exchanging the dimethylimino groups with the secondary amine and addition of the amine at the 2-position of the pyran or thiapyran ring.     

Poly(enamine-ketones) from hydrogen-terminated aromatic dipropynones and aromatic diamines

Poly(enamine-ketones) were prepared by the nucleophilic (Michael-type) addition of various aromatic diamines to 1,1′-(1,3- or 1,4-phenylene)bis(2-propyn-1-one)(1,3 or 1,4-PPO) in m-cresol at 5–23°C. The low molecular weight polymers (inherent viscosity of 0.25 dL/g) exhibited limited solubility in organic solvents. Glass transition temperatures were generally undetectable by differential scanning calorimetry while polymer decomposition temperatures (10% weight loss), as measured by thermogravimetric analysis, were observed from 355 to 419°C. Polymers prepared from 1,4-PPO were semi-crystalline as shown by wide-angle X-ray diffraction. The poly(enamine-ketone) structure was confirmed by matching infrared spectral characteristics of the polymers with those of well-characterized model enamine ketones.     

Synthesis and spectral studies of macrocyclic Cu(II) complexes by reaction of various diamines,copper(II) perchlorate and 1,4-bis(2-carboxyaldehyde phenoxy)butane

Six macrocyclic complexes, were synthesized by reaction of 1,4-bis(2-carboxyaldehyde phenoxy)butane and various amines and their copper(II) perchlorate complexes were synthesized by template effect reaction of 1,4-bis(2-carboxyaldehyde phenoxy)butane, Cu(ClO₄)₂?·?6H₂O and amines. The metal-to-ligand ratios were found to be 1?:?1. Cu(II) metal complexes are 1?:?2 electrolytes as shown by their molar conductivities (Λ_M) in DMF (dimethyl formamide) at 10^?3?M. The Cu(II) complexes are proposed to be square planar based on elemental analysis, FT–IR, UV–Vis, magnetic susceptibility measurements, molar conductivity measurements, and mass spectra.     

Reaction of 3-Arylaminobenzofuro-, 3-Arylaminobenzothieno-, and 3-Arylaminoindolo[2,3-<Emphasis Type="Italic">c</Emphasis>]pyrylium Salts with Nucleophilic Reagents

We have studied the reactions of 3-arylaminobenzofuro-, 3-arylaminobenzothieno-, and 3-arylaminoindolo[2,3-c]pyrylium salts with ammonium acetate, primary amines, and hydrazine hydrate. In an alcoholic medium, primary amines and hydrazine hydrate open up the pyrylium ring to form arylamides of 2-(N-benzylmethylketimine)hetaryl-3-acetic acids or the corresponding hydrazones, where further heterocyclization does not occur. Upon treatment with ammonium acetate in acetic acid, 2-aryl-1-methylhetero[2,3-c]pyridin-3-(2H)-ones are formed along with their 2-unsubstituted analogs.__________Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 601–612, April, 2005.     

Pyrylium salts from pyrones and some organometallic compounds

Pyrones and their analogs react with methyl bromoacetate and methyl -bromocrotonate in the presence of activated zinc to give, ultimately, carbomethoxymethyl- or (3-carbomethoxy-2-propenyl)-substituted pyrylium salts. The Ivanov reagent from phenylacetic acid reacts with pyrones to give carboxybenzyl-substituted pyrylium salts.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1317–1320, October, 1973.     

On triazoles XLIX. Synthesis of 5,6‐dihydrothiazolo[3,2‐b]‐[1,2,4]triazol‐2‐yl‐, 6,7‐dihydro‐5H‐[1,2,4]triazolo[5,1‐b][1,3]thiazin‐2‐yl‐, and 5,6,7,8‐tetrahydro[1,2,4]triazolo[5,1‐b] [1,3]thiazepin‐2‐yl‐isoquinolinium salts

5′‐Mercapto‐1′H‐1,2,4‐triazol‐3′‐yl‐isoquinolinium salts (6) were synthesised by the reaction of ortho‐acyl phenylacetones (2) or the corresponding pyrylium salts (3) and 5‐amino‐2,3‐dihydro‐1H‐1,2,4‐triazole‐3‐thione (5) . Treatment of thioles 6 withα,ω‐dibromoalkanes led to type 15, 16 and 17 isoquinolinium salts condensed with thiazole, thiazine and thiazepine rings. When 6 are reacted with dibromomethane (10) 11 type dimeric structures are obtained.