Recent Developments in Acenaphthoquinone-Based Multicomponent Reactions: Synthesis of Spiroacenaphthylene Compounds

Abstract

This review characterizes the multicomponent reactions of acenaphthoquinone as building blocks for the synthesis of a variety of heterocyclic compounds with medicinal chemistry interest. There is a wide range of reactions that include acenaphthoquinone in the synthesis of heterocyclic compounds. Also this review gives an overview spirocyclic compounds has important applications in pharmacological during the period from 2000 to 2017. Spiro compounds having cyclic structures fused at a central carbon are of recent interest due to their interesting adjustable overall qualities and their structural implications on biological systems.

1 Introduction

Acenaphthoquinones are interesting with regard to photochemistry [1, 2], synthetic photochemistry [3, 4], and versatile synthetic intermediates to polycyclic hydrocarbon [5] and heterocyclic compounds [6]. The most widely used methods for the preparation of acenaphthoquinone are the oxidation of acenaphthene with various oxidizing agents [7] and the Friedel–Crafts reaction of naphthalene derivatives with oxalyl chloride [8]. Multicomponent reactions (MCRs) play an increasingly important role in organic and medicinal chemistry because of their convergence, productivity, ease of execution, good to excellent yields, and broad applications in combinatorial chemistry [9,10,11]. Also, multicomponent reactions are generally defined as reactions where more than two starting materials react to form a product, incorporating essentially all of the atoms of the educts. Such reactions provide a number of valuable conceptual and synthetic advantages over stepwise sequential approaches towards complex and valuable molecules. They are atom economic, efficient, and extremely convergent. Such strategies reduce the number of steps in the reactions, thus avoiding the complicated purification procedures and allowing saving of both solvents and reagents [12, 13]. Acenaphthoquinone as privileged molecules in the design and synthesis of spiro-fused cyclic frameworks like spiro[4H-pyran] derivatives, spiro acenaphthylenes, dispiro oxindolopyrrolidines/pyrrolizidines, spiro[indoline-3,2′-quinazoline, dispirodihydrofuranyl oxindoles, spiro1H-pyrrolo[2,3-b]pyridines, spiro dihydropyridines, spiro[isoindoline-1,2′-quinazoline, etc. Also used in the preparation propellans as polycyclic pyrroles. 4H-pyrans derivatives have been considered because their pharmacological activity [14], which includes spasmolytic, diuretic, anti-coagulant, anti-anaphylactic activity [14,15,16,17], anti-cancer [18], cytotoxic [19], anti-HIV [20,21,22], anti-inflammatory [23], anti-malarial [24, 25], anti-microbial [26], anti-hyperglycemic and anti-dyslipidemic [27], and anti-neurodegenerative disorders like Alzheimer’s, Parkinson’s, and Huntington’s disease [28,29,30]. Most the reaction in his review are atom-efficient, high yielding, short reaction time, environmental friendliness, easy work-upand follows a simple experimental procedure.

2 Acenaphthoquinone Synthesis

Synthesis of acenaphthoquinone 1 from 1-acenaphthenone 2 with N-bromosuccinimide was carried out in dimethyl sulfoxide at room temperature. Under similar conditions, several acenaphthoquinones were prepared from the corresponding 1-acenaphthenones in good yields (Scheme 1) [30].

Scheme 1

Acenaphthoquinone synthesis

3 Synthesis of Oxazo[3.3.3] Propellane

Yan et al. reported three-component synthesis of oxazo[3.3.3]propellane 5 using acenaphthylene-1,2-dione 1, heterocyclic ketene aminals (HKAs) 4 and ethyl trifluoroacetylacetate 3, bearing four consecutive quaternary stereo-centers (Scheme 2) [31].

Scheme 2

Synthesis of oxazo[3.3.3]propellane

4 Synthesis of Spiro[acenaphthylene-imidazo pyridine]carbonitrile Compounds

Shao and coworkers discovered that the reaction between ketene aminals 6, acenaphthoquinone 1 and ethyl cyanacetate 7 in DMF, at 70 °C, resulted in the formation of 2-oxo-1,2-dihydropyridine-spiro 1,3-diaza heterocycles 8 with excellent yields (Scheme 3) [32]. A mechanism involving aza–ene, imine–enamine tautomerization followed by cyclization was proposed (Scheme 4).

Scheme 3

Synthesis of spiro[acenaphthylene-1,7′-imidazo[1,2-a]pyridine]-6′-carbonitrile

Scheme 4

Proposed mechanism for the formation of spiro[acenaphthylene-1,7′-imidazo[1,2-a]pyridine]-6′-carbonitrile

5 Synthesis of Spiro-dihydropyridine Derivatives

In 2016, Hasaninejad’s group reported the synthesis of spiro-dihydropyridine derivatives 13 by one-pot multicomponent reaction of acenaphthoquinone derivatives 1 with malononitrile 7 and N,N′-substituted-2-nitroethene-1,1-diamines 12 in PEG-400 under catalyst-free conditions (Scheme 5) [33].

Scheme 5

Synthesis of spiro-dihydropyridine derivatives

In 2014, Li and coworkers discovered synthesis of spiro-dihydropyridines derivatives 16 of acenaphthoquinone 1, malononitrile 7 and HKAs 15 without the catalysts in CH₂CH₂/MeOH at room temperature (Scheme 6) [34].

Scheme 6

Synthesis of spiro-dihydropyridines derivatives

An efficient synthesis of a series of spiro dihydropyridine derivatives 19 was developed via one-pot four-component reaction of diketone 1, malononitrile 7, primary amines 17, and acetylenic esters 18 in good yield (Scheme 7) [35]. A plausible mechanism of this four-component reaction is presented in Scheme 8.

Scheme 7

Synthesis of a series of spiro dihydropyridine derivatives

Scheme 8

Plausible mechanism for the formation of 2-oxospiro-[acenaphthyl-3,4′-(1′,4′-dihydropyridine)] derivatives

Initially, acenaphthoquinone 1 undergoes Knoevenagel condensation with malononitrile 7 in the presence of Et₃N to afford component 14. m-Toluidine 17 adds on to DMAD 18 to give the zwitterionic intermediate 20, which undergoes Michael addition with 14 to form 21 and then through the migration of hydrogen atom obtained 22. The intramolecular addition of the amino group to the cyano triple bond provides 23, which tautomerizes to give 19 (Scheme 8).

6 Synthesis of Spiro-indenopyridine Derivatives

l-Proline was found to be a versatile organo-catalyst for the synthesis of new spiro[acenaphthylene-indeno[1,2-b]pyridine] derivatives 26 developed by Bazgir et al. in a one-pot, three-component (MCR) approach involving substituted acenaphthoquinone 1, 1H-indole-2,3-diones 24, enamines 25 under mild reaction conditions using 1-propanol as a solvent in good yields as shown in Scheme 9 [36].

Scheme 9

Synthesis of spiro[acenaphthylene-indeno [1,2-b]pyridine] derivatives

In a study by Ghahremanzadeh and coworkers, a synthetic route to highly functionalized spiro[acenaphthylene-diindenopyridine]triones 27 was developed via a one-pot, four-component domino reaction of 1,3-indandione 24, aromatic amines 17, acenaphthylene-1,2-dione 1 using a ‘Grindstone Chemistry’ method/in refluxing acetonitrile conditions with p-TSA (Scheme 10) [37]. A reasonable mechanism for the formation of spiro[diindenopyridine-indoline]triones 27 is shown in Scheme 11. The mechanism involves the formation of intermediate 28 from 1,3-indanedione 24 to the acenaphthoquinone 1, which reacted further with another molecule of 24. Finally, addition of the substituted aniline 17 to the intermediate 29, followed by cyclization afforded the product 27 (Scheme 11).

Scheme 10

One-pot synthesis of spiro[acenaphthylene-diindenopyridine]triones

Scheme 11

Proposed mechanism for the synthesis of spirodiindenopyridine-indolines 27

A new four-component synthesis of spiro-[acenaphthylene-1(2H),4′-[4H-indeno[1,2-b]pyridines] 33 was described by the reaction of acenaphthylene-1,2-dione 1, indane-1,3-dione 24, 1,3-dicarbonyl compounds 32, and NH₄OH 31 in toluene at reflux. The preparation method is efficient and convenient and the presence of a catalytic amount of pyridine is required. (Scheme 12) [38].

Scheme 12

Synthesis of spiro-[acenaphthylene-1(2H),4′-[4H-indeno[1,2-b]pyridines]

In 2002, Nair et al. accomplished the zwitterion generated from diisopropylaminoisocyanide 34 and dimethyl acetylenedicarboxylate (DMAD) 18 with acenaphthoquinone 1 in benzene under reflux in an atmosphere of argon to the synthesis of dimethyl 1′-(diisopropylamino)-2,5′-dioxo-1′,5′-dihydro-2H-spiro[acenaphthylene-1,2′-pyrrole]-3′,4′-dicarboxylate 35 (Scheme 13) [39].

Scheme 13

Synthesis of spiro[acenaphthylene-1,2′-pyrrole]-3′,4′-dicarboxylate

7 Synthesis of Spiro-pyrrole Derivatives

Reaction of acenaphthoquinone 1 and N-isocyano-N-isopropylpropan-2-amine 34 with dimethyl acetylenedicarboxylate (DMAD) 18 afforded synthesis of dimethyl 1′-(diisopropylamino)-2,5′-dioxo-1′,5′-dihydro-2H-spiro[acenaphthylene-1,2′-pyrrole]-3′,4′ dicarboxylate 35 (Scheme 14) [40].

Scheme 14

Synthesis of spiro[acenaphthylene-1,2′-pyrrole]-3′,4′-dicarboxylate

8 Synthesis of Spiro-oxazine Derivatives

In 2015, Zhang and Yan described a reaction between α,β-unsaturated N-arylaldimines 37, dialkyl acetylenedicarboxylate 18 and acenaphthenequinone 1 in dry acetonitrile without a catalyst for the synthesis of structurally diverse spirocyclic 1,3-oxazines 38 in good yields (Scheme 15) [41]. A proposed mechanism for the formation of spiro[acenaphthylene-1,6′-[1,3]oxazines] three-component reaction is shown in Scheme 16. The first step is the nucleophilic addition of aldimine to acetylenedicarboxylate affords the desired 1,4-dipole 39. Secondly, this 1,4-dipolar intermediate 40 attacks one carbonyl group of 1,4-naphthoquinone and results in the zwitterionic intermediate 41. Thirdly, the intramolecular attack of negative oxygen to the iminium salt in intermediate 41 gives the final spiro[acenaphthylene-1,6′-[1,3]oxazines] and a mixture of cis/trans-diastereoisomers 38 was obtained (Scheme 16).

Scheme 15

Synthesis of spiro[acenaphthylene-1,6′-[1,3]oxazines]

Scheme 16

A proposed mechanism for the formation of spiro[acenaphthylene-1,6′-[1,3]oxazines]

9 Synthesis of Spiro-oxadiazole and Oxazole Derivatives

Ramazani et al. discovered that reactions of (N-isocyanimino)triphenylphosphorane 43 with acenaphthoquinone 1 in the presence of aromatic carboxylic acids 42 proceed smoothly at room temperature and under neutral conditions to afford sterically congested 1,3,4-oxadiazole derivatives 44 in high yields (Scheme 17) [42]. A plausible mechanism for the reaction is shown in Scheme 18. The first step may involve nucleophilic addition of (N-isocyanimino) triphenylphosphorane 28 to acenaphthoquinone 1, by the acid 42 as catalyst, leading to nitrilium intermediate 46. This intermediate may be attacked by the conjugate base of acid to form 1:1:1 adduct 47. This adduct under intramolecular aza-Wittig reaction of the iminophosphorane moiety with the ester carbonyl was obtained 1,3,4-oxadiazole derivatives 44 by elimination of triphenylphosphine oxide 45 from intermediate 48 (Scheme 18).

Scheme 17

Synthesis of 1,3,4-oxadiazole 2-hydroxyacenaphthylen-1(2H)-one

Scheme 18

Proposed mechanism for the synthesis of 29

In 2015, Nadji-Boukrouche’s group reported 5-(dibromomethyl)-3-methyl-6 nitrobenzoxazolone 49 reacted with acenaphthoquinone 1 catalyzed by tetrakis (dimethylamino) ethylene (TDAE) in DMF under stirred at 20 °C for 1 h and then warmed to room temperature for 2 h to yield for synthesis of 5-((1-hydroxy-2-oxo-1,2-dihydroacenaphthylen-1-yl)methyl)-3-methyl-6-nitrobenzo[d]oxazol-2(3H)-one 50 (Scheme 19) [43].

Scheme 19

Synthesis of 5-((1-hydroxy-2-oxo-1,2-dihydroacenaphthylen-1-yl)methyl)-3-methyl-6 nitrobenzo[d]oxazol-2(3H)-one

10 Synthesis of Acenaphthylen-1-one Derivatives

Acenaphthoquinone 1 was found to react smoothly with nonstabilized azomethine ylides, generated in situ from sarcosine/formaldehyde or N-(methoxymethyl)-N-(trimethylsilylmethyl)benzylamine, to give 2-hydroxy-2-((methylamino)methyl)acenaphthylen-1(2H)-one 51, which were converted into 2-alkylaminoethanols in moderate-to-good yields by heating in n-butanol with hydrochloric acid (Scheme 20) [44].

Scheme 20

Synthesis of 2-hydroxy-2-((methylamino)methyl)acenaphthylen-1(2H)-one

A series of 2-hydroxy-2-(4,5,5-trimethoxy-6-oxocyclohexa-1,3-dien-1-yl)acenaphthylen-1(2H)-one 53 was prepared by Chittimalla and coworkers who did reactions of acenaphthoquinone 1, o-benzoquinone (MOB; 6,6-dimethoxy-cyclohexa-2,4-dienone derivatives) derivatives 52 in THF/H₂O at room temperature (Scheme 21) [45].

Scheme 21

Synthesis of 2-hydroxy-2-(4,5,5-trimethoxy-6-oxocyclohexa-1,3-dien-1-yl)acenaphthylen-1(2H)-one

11 Synthesis of Spiro-oxazino Isoquinoline Derivatives

The reaction of 1,2,3,4-tetrahydroisoquinoline 54 and acenaphthoquinone 1 with dimethyl acetylenedicarboxylate 18 was investigated in a one-pot, three-component process for synthesis of a variety of [1,3]oxazino isoquinoline 55 via 1,4-dipolar cycloaddition (Scheme 22) [46].

Scheme 22

Synthesis of [1,3]oxazino isoquinoline

12 Synthesis of Spiro-thiazolidine and Thiazine–Dione Derivatives

Treatment of acenaphthylene-1,2-dione 1 with substituted anilines 17, and a mercaptocarboxylic acid 56 in the presence of thiamine hydrochloride [vitamin B1 (VB1)] as catalyst was developed for the synthesis of spiro[acenaphthylene-1,2′[1,3]-thiazolidine]-2,4′(1H)-diones 57 in water at 80 °C temperature (Scheme 23) [47].

Scheme 23

Synthesis of spiro[acenaphthylene-1,2′[1,3]-thiazolidine]-2,4′(1H)-diones

Anshu Dandia et al. developed a new synthesis of medicinally important spiro[acenaphthylene-1,2′-[1,3]thiazine]dione 59 via the one-pot reaction of acenaphthylene 1,2-dione 1, substituted anilines 17 with 3-mercaptopropionic acid 58 in 1-butyl-3 methylimidazolium hexafluorophosphate [bmim][PF₆] at 80 °C (Scheme 24) [48].

Scheme 24

Synthesis of spiro[acenaphthylene-1,2-[1,3]thiazine]-2,4-diones

13 Synthesis of Acenaphtho[1,2-b]indole Derivatives

Chen et al. reported the preparation of acenaphtho[1,2-b]indoles, which can be accessed in a one-step, two-component reaction between enaminones 60 with acenaphthoquinone 1. During the first pathway, product 61 was synthesized in the presence of Et₃N, while a second reaction in the presence of p-toluenesulfonic acid leads to compound 62 via intramolecular cyclization and highly regioselective SN₁-type reaction with alcohols under solvent-free conditions with excellent yields (Scheme 25) [49].

Scheme 25

Synthesis of acenaphtho[1,2-b]indoles

14 Synthesis of Dihydroxy Acenaphtho[1,2-b]indolone Derivatives

In 2015, Das et al. reported the procedure for the synthesis of dihydroxy acenaphtho[1,2-b]indolone derivatives 64 in aqueous medium catalyzed by a tin oxide (SnO₂) quantum dot (QD). The reaction was performed by the treatment of acenaphthenequinone 1, 1,3-dicarbonyl compounds 63, and aromatic amines 17 at 70 °C for 2-3 h (Scheme 26) [50].

Scheme 26

Synthesis of dihydroxy acenaphtho[1,2-b]indolone derivatives

15 Synthesis of Hydroxypyrrole Derivatives

A one-pot synthesis of pyrrole derivatives 65 via reaction between acenaphthoquinone 1, 1,3-dicarbonyls 32, and primary amines 17 under solvent-free conditions is described (Scheme 27) [51]. A tentative mechanism for this transformation is proposed in Scheme 28. It is conceivable that the reaction involves the initial formation of enaminones 66 between 1,3-dicarbonyls 32 and primary amines 17. Enaminones that are formed under solvent-free conditions react with the carbonyl group of 1 and produced 67. Cyclization of this intermediate leads to the compound 65 (Scheme 28).

Scheme 27 and 28

Synthesis of pyrrole derivatives

16 Synthesis of Tetrahydroacenaphtho[1,2-b]indolone Derivatives

Three-component reaction of acenaphthoquinone 1, enaminones 60, was accomplished with barbituric acid 68 by Liu et al. using l-proline (10 mol%) as catalyst in refluxing ethanol. This efficient method gave the synthesis of tetrahydroacenaphtho[1,2-b]indolone derivatives 69 with good yields (Scheme 29) [52]. Mechanistic representation for synthesis of tetrahydroacenaphtho[1,2-b]indolone derivatives is shown in Scheme 30. Reaction of the acenaphthylene-1,2-dione 1 with l-proline to afford iminum ion 71. The intermediate 72 was formed by the Knoevenagel condensation of iminum ion 71 with barbituric acid 68, and elimination of l-proline. Then the Michael addition of intermediate 73 with enaminones 60 would give the intermediate 72, after with intramolecular cyclization to generated 69 (Scheme 30).

Scheme 29

Synthesis of tetrahydroacenaphtho[1,2-b]indolone derivatives

Scheme 30

Proposed mechanism for the synthesis of 49

17 Synthesis of Pentacyclic and Tetracyclic Indole Derivatives

A new multicomponent domino reaction of cyclic enaminones 60 with acenaphthylene-1,2-dione 1 for synthesis of pentacyclic indoles 75, 76, 77, 78 by Li and coworkers with good to excellent yields in an anhydride solvent has been established, providing selective protocol to pentacyclic indoles with different substituted patterns (Scheme 31) [53].

Scheme 31

Synthesis of pentacyclic indoles

An efficient method has been developed by Yugandar and coworkers for the synthesis of novel tetracyclic indole derivatives 80 via a one-pot, three-component condensation reaction of tetracyclic indole derivatives 79 in high yields, in DMF at 120 °C in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) on treatment with various active methylene such as ethyl 2-cyanoacetate/4-pyridylmethyl nitrile/2-(4-chlorophenyl)nitrile 7, respectively, under identical conditions (Scheme 32) [54].

Scheme 32

Synthesis of tetracyclic indoles

18 Synthesis of Imidazole Derivatives

In 2015, Mokhtary et al. synthesized three-component condensation of acenaphthenequinone 1 with aryl aldehyde 81 and ammonium acetate to generate highly substituted imidazole derivatives 82 over tin oxide nanoparticles as catalyst in ethanol under reflux conditions (Scheme 33) [55].

Scheme 33

Synthesis of imidazole derivatives

In Scheme 34, it was assumed that the SnO₂ nanoparticles can be used to active the carbonyl group of aldehydes and facilitate the formation of a diamine intermediate. The later, the condensation of the diamine intermediate with acenaphthenequinone, intramolecular cyclization and then tautomeric [1,5] proton shift the corresponding 8-aryl-7H-acenaphtho[1,2-d]imidazole derivatives (Scheme 34).

Scheme 34

Synthesis of imidazole derivatives

Reaction of acenaphthoquinone 1 with benzaldehyde 81 in the presence of ammonia had been reported to afford 8-phenyl-7H-acenaphtho[1,2-d]imidazole 82 (Scheme 35) [56].

Scheme 35

Synthesis of phenyl-7H-acenaphtho[1,2-d]imidazole

19 Synthesis of Spiro-benzoimidazoisoquinolin Quinazolinone Derivatives

Reaction of acenaphthoquinone 1 with benzyl 85, and ammonium acetate 31 under solvent-free conditions had been reported to 9,10-diaryl-7H-benzo[d, e]imidazo[2,1-a]isoquinolin-7-ones 86 in good to excellent yields (Scheme 36) [57]. The suggested mechanism for the formation of products 86 is illustrated in Scheme 37.

Scheme 36

Synthesis of benzo[d,e]imidazo[2,1-a]isoquinolin-ones

Scheme 37

Proposed mechanism for the synthesis of 59

In 2016, Sawant’s group a novel multicomponent route has been discovered for the synthesis of spiro-benzimidazoquinazolinones 93 under microwave irradiation. It involves a one-pot, three-component reaction of acenaphthoquinone 1, 1,3-diketone (63, 24) and 2-aminobenzimidazole 92 in ethanol at 180 W and 160 °C temperature (Scheme 38) [58]. A possible mechanism for the formation of 93 is proposed in Scheme 39. It is reasonable to assume that 93 results from initial formation of a hetero-diene 94 by standard Knoevenagel condensation of the dimedone 63a and acenaphthoquinone 1. Then, the subsequent Michael-type addition of the 2-aminobenzimidazole 92 to the heterodyne 95, followed by cyclization affords the corresponding products 93 (Scheme 39).

Scheme 38

Synthesis of spiro-benzimidazoquinazolinones

Scheme 39

Proposed mechanisms for the synthesis of spirobenzimidazoquinazolinone

20 Synthesis of Spiro-pyrrolo-thiazole Derivatives

Synthesis of spiro[acenaphthylene-1,5′-pyrrolo[1,2-c]thiazole] derivatives 64 has been achieved by a one-pot, three-component reaction through 1,3-dipolar cycloaddition of acenaphthenequinone 1, 1,3-thiazole-4-carboxylic acid 62 and Knoevenagel adduct 63 in aqueous medium in the presence of NaCl (Scheme 40) [59].

Scheme 40

Synthesis of spiro[acenaphthylene-1,5′-pyrrolo[1,2-c]thiazole] derivatives

21 Synthesis of Diazahexacyclo-henicosa-pentaen-one Derivatives

Kumar and coworkers reported that the one-pot pseudo-three-component [3 + ‏2]-cycloaddition between the N-unsubstituted 3,5-bis[(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones 100, sarcosine 99 and acenaphthoquinone 1 afforded derivatives of diazahexacyclo-henicosa-pentaen-ones 101 in good to excellent yields and isolated as the sole reaction product. The ring systems thus generated contain as structural elements bridged, fused, and spiro rings and were obtained with complete selectivity through the creation of two C–C and two C–N bonds, which led to the generation of two azaheterocyclic rings, four carbon and one nitrogen adjacent stereo-centers, three of which are quaternary (Scheme 41) [60]. The proposed mechanism for the synthesis of 101 is summarized in Scheme 42 for the case of the diazapentacycle 101. The reaction of acenaphthoquinone 1 and sarcosine 99 affords the azomethine ylide 102, which adds to one of the C=C bonds of the bisdipolarophile 100 to form the corresponding cycloadduct 103. The final attack an amino group to the neighboring carbonyl group led to formation component 101 (Scheme 42).

Scheme 41

Synthesis of hydroxy-tetrahydro-methanoacenaphtho[1,2-[1,2-b]]pyrrolo[2,3-c]azepin-one

Scheme 42

Mechanistic proposal to explain the formation of compounds 67 through a domino sequence

22 Synthesis of Hybrid Heterocyclic Systems

Arumugam et al. has developed an expedient regio-stereo and product-selective synthesis of novel hybrid heterocyclic systems 105 comprising [1,2-c]oxazolidine, pyrrolidine and piperidine units, in good to excellent yields, via a three-component reaction of acenaphthoquinone 1 with l-phenylalanine 104 and 3,5-dibenzylidenepiperidin-4-one 100 in methanol under heating at reflux. Also, the reaction of 105 with para-formaldehyde proceeded in a highly product-selective manner furnishing solely the heptacyclic ring system 106 (Scheme 43) [61].

Scheme 43

Synthesis of hybrid heterocyclic

23 Synthesis of Spiro-pyrazolo-thiazepine Derivatives

One-pot reaction of acenaphthoquinone 1, 5-amino-3-methylpyrazole 107, and thioacid 108 in CH₃CN in the presence of catalyst p-TSA gave spiro[acenaphthylene-1,4′-pyrazolo[3,4-e][1,4]thiazepine]-2,7′ (1′ H)-dione derivatives 109 (Scheme 44) [62]. A plausible mechanism that could account for the three-component reaction is given in Scheme 45. The first step involves the formation of a Baylis–Hillman type adduct 110 by the nucleophilic addition of 5-amino-3-methylpyrazole 107 to acenaphthoquinone 1 as a intermediate, which may occur to afford 111. Then, 111 is attacked via Michael addition of thioacid 108 to give the intermediate 112 followed by cycloaddition, dehydration, to form the corresponding product 109 (Scheme 45).

Scheme 44

Synthesis of spirocyclic acenaphthyleneones

Scheme 45

Plausible mechanism for the formation of 2-oxospiro-[acenaphthyl-3,4′-(1′,4′-dihydropyridine)] derivatives

24 Synthesis of Dispiro-estrone-trans-androsterones Hybrid Heterocycle Derivatives

The 1,3-dipolar cycloaddition of azomethine ylides generated in situ from the reaction of acenaphthylene-1,2-dione 1 and 1,3-thiazolane-4-carboxylic acid 96 to various exocyclic dipolarophiles synthesized from estrone 114 at reflux i-PrOH for 3 h afforded a library of novel spiroacenaphthylene-1-one-7-(aryl)tetrahydro-1H-pyrrolo[1,2-c][1,3]thiazole estrone hybrid heterocycles 115 (Scheme 46) [63].

Scheme 46

Synthesis of spiro-acenaphthylene-spiro-tetrahydro-1H-pyrrolo[1,2-c][1,3]thiazolo estrone hybrid heterocycles

In 2013, Kumar et al. discovered the 1,3-dipolar cycloaddition of azomethine ylide derived in situ from the reaction of acenaphthylene-1,2-dione 1 and 1,3-thiazolane-4-carboxylic acid 96 to various exocyclic dipolarophiles from trans-androsterone 116 and trans-dehydroandrosterone 114 afforded a library of novel spiro[5′.2″]acenaphthylene-1″-one-spiro[16.6′]-(7′-aryl) tetrahydro-1H-pyrrolo [1,2-c][1,3]thiazolo-trans-androsterone/dehydroandrosterone hybrid heterocycles 115 and 117, respectively (Scheme 47) [64].

Scheme 47

Synthesis of spiro[5′.2″]acenaphthylene-1″-one-spiro[16.6′]-(7′-aryl)-tetrahydro-1H-pyrrolo [1,2-c][1,3]thiazolo-trans-androsterone/dehydroandrosterone hybrid heterocycles

25 Synthesis of Bispiropyrrolidine Derivatives

Banerjee’s group afforded an efficient synthesis of bispiropyrrolidine derivatives 119 through 1,3-dipolar cycloaddition reaction of a carbohydrate-derived exocyclic olefin 118 with in situ-generated nonstabilized azomethine ylides, formed by the reaction of sarcosine (a secondary α-amino acid) 96 with acenaphthenedione 1 and cycloalkanones in refluxing toluene, when DIPEA was used as a base (Scheme 48) [65].

Scheme 48

Synthesis of bispiropyrrolidine derivatives

26 Synthesis of Carbohydrate-Derived Spiro Heterocycles

In 2015. Raghunathan et al. reported a facile one-pot synthesis of carbohydrate-derived spiro heterocycles 123-126 via [3 + 2] cycloaddition reaction of azomethine ylides. A unique dipolarophile(4-oxo-2-glyco-4H-chromene-3-carboxylate) 120 synthesized from d-glucose reacted with azomethine ylide generated in situ from secondary α-amino acids (sarcosine 99, proline 96, or pipecolinic acid 121, tetrahydroisoquinoline-3-carboxylic acid 122) and 1,2-diketone (acenaphthoquinone) 1 to give their corresponding cycloadducts in good yield (Scheme 49) [66].

Scheme 49

Synthesis of carbohydrate-derived pyrrolidinyl-spiro acenaphthylenones

27 Synthesis of Spiropyrrolidine and Spiropyrrolizidine Derivatives

Tabatabaei Rezaei et al. studied the regio-selective synthesis of spiropyrrolidine and spiropyrrolizidine 127 and 128 via the multicomponent condensation of azomethine ylides (generated in situ from amino acids 96 and 99 viz. sarcosine/N-phenylglycine/proline and acenaphthenequinone 1) with the Knoevenagel adduct derivatives 97 (preformed by the reaction of malononitrile with substituted benzaldehydes). The reactions were carried out under both conventional heating and ultrasonic irradiation conditions (Scheme 50) [67].

Scheme 50

Synthesis of spiropyrrolidine and spiropyrrolizidine

An efficient synthesis of novel spiro[acenaphthylene-1,2′-pyrrolidine] 127, spiro[acenaphthylene-1,2′-pyrrolizidine] 128, containing cyano group were successfully synthesized via a three-component 1,3-dipolar cycloaddition reaction of acenaphthenequinone 1, sarcosine or proline 96 and 99, and Knoevenagel adducts 97 in refluxing aqueous methanol (Scheme 51) [68].

Scheme 51

Synthesis of spiro[acenaphthylene-pyrrolidine] 87, spiro[acenaphthylene-pyrrolizidine] 88

The synthesis of novel glyco-spiro-pyrrolidines and glyco-spiro-pyrrolizidines 130, 132, and 133 has been accomplished through 1,3-dipolar cycloaddition reaction of various azomethine ylides derived from acenaphthoquinone 1 and secondary amino acids 99, 96 with glycoacrylate 129, 131 as dipolarophile (Schemes 52, 53) [69].

Scheme 52

Synthesis of glycopyrrolidine

Scheme 53

Synthesis of glycopyrrolizidines

The synthesis of new spiropyrrolidines/pyrrolizidines 135, 136 has been achieved by Ramesh and coworkers. Baylis–Hillman adduct (of ninhydrin with sarcosine/proline) as dipolarophiles 134 were reacted with azomethine ylides, generated in situ from sarcosine 99, 96 and acenaphthoquinone 1, to produce the corresponding cycloadducts in various condition. The other regioisomers 135a and 136a were not formed (Method A: conventional methanol reflux, Method B: methanol/MW, Method C: K-10 Montmorillonite clay/MW) (Schemes 54, 55) [70].

Scheme 54

Synthesis of novel spiropyrrolidines

Scheme 55

Synthesis of novel spiropyrrolizidines

Raghunathan et al. developed an efficient three-component protocol to synthesize acridine-dione-derived mono spiro-pyrrolidine and pyrrolizidine derivatives 138, 139 by 1,3-dipolar cycloaddition reaction. The o-acryloylacridine-diones 137, as dipolarophiles reacted with azomethine ylide derived from diketones 1 and sec-amino acids 99, 96 to give acridinedione-derived mono spiropyrrolidine/pyrrolizidine derivatives in good yield (Scheme 56) [71].

Scheme 56

Synthesis of mono spiroacenaphtheno/indano-pyrrolidine/pyrrolizidine derivatives

Vijay et al. reported the reaction of isatin 140, sarcosine 99, and acenaphthenequinone 1 and 3,4-diphenyl cyclobutene-1,2-dione 142 in methanol:water (3:1) furnishing novel spiropyrrolidine derivatives 141 and 143 (Scheme 57) [72].

Scheme 57

Synthesis of spiropyrrolidine derivatives

A novel spiro[acenaphthylene-1,2′-pyrrolidin]-2-one derivatives 146 was synthesized via the three-component, one-pot reaction of acenaphthenequinone 1, arylmethyl amines 144, and chalcones 145 with high regioselectivity in ethanol without any catalyst for 90 min (Scheme 58) [73].

Scheme 58

Synthesis of spiro[acenaphthylene-1,2′-pyrrolidin]-2-one derivatives

The suggested mechanism for the formation of product 146 is illustrated in Scheme 59. The reaction of acenaphthenequinone 1 with arylmethyl amines 144 led to the formation of the azomethine ylides 147, which is used as dipoles. The carbanion of azomethine ylides 147 then assaulted the electrophilic β-carbon of chalcones, the products 146 were afforded (Scheme 59).

Scheme 59

Plausible mechanism for the synthesis of spiro[acenaphthylene-1,2′-pyrrolidin]-2-one derivatives

28 Synthesis of Dispiropyrrolidine/Pyrrolizidines Thiapyrrolizidine Derivatives

A series of novel dispiropyrrolidine derivatives 150 has been accomplished through 1,3-dipolar cycloaddition reaction of azomethine ylide generated from sarcosin 65 and acenaphthoquinone 1 with the dipolarophile (E)-2-arylidine-1-keto-carbazoles 149. The cycloadducts ketocarbazalo spiro N-methyl pyrrolidines showed the most interesting antimicrobial activity at lower concentration (Scheme 60) [74].

Scheme 60

Synthesis of novel dispiropyrrolidine derivatives

The synthesis of novel dispiroheterocycles 152 by the cycloaddition reaction of azomethine ylides generated from sarcosine 99 and acenaphthoquinone 1 with (E)-3-furfurylidene-4-chromanone/(E)-2-furfurylidene-1-tetralone 151 was described by Manian et al. (Scheme 61) [75].

Scheme 61

Synthesis of novel dispiroheterocycles derivatives

The reaction of 2-[(E)-1-arylmethylidene]-1-indanones 153 with acenaphthoquinone 1 and sarcosine 99 in MeOH at reflux afforded synthesis of highly functionalized dispiropyrrolidines 154 using [3 + 2]-cycloaddition by Ali et al. (Scheme 62) [76].

Scheme 62

Synthesis of highly functionalized dispiropyrrolidines

A plausible mechanism for the formation of the novel pyrrolidine derivative is given in Scheme 63. The reaction of acenaphthenequinone 1 and sarcosine 99 to give the azomethine ylide 156, which adds to C=C bond of the dipolarophile from the bottom to form the desired cycloadduct. Eventually, only one stereoisomer of the cycloadduct despite of the presence of three stereocenters (Scheme 63).

Scheme 63

Mechanism for the regioselective formation of dispiropyrrolidine

A new dispiro compound 158 was regioselectively synthesized by a one-pot, multicomponent reaction of acenaphthoquinone 1, thiophenone ring 157, and sarcosine 99. Unsaturated thiophenone dipolarophiles were reacted with azomethine ylides, generated in situ from sarcosine, acenaphthoquinone, to produce the corresponding cycloadducts in good yields (70–90%) (Scheme 64) [77].

Scheme 64

Synthesis of dispiro compound

A synthetic route for the preparation of novel synthesis of novel dispiropyrrolidin/pyrrolizine derivatives 160 and 161 has been accomplished via 1,3-dipolar cycloaddition of azomethineylides generated in situ by the decarboxylative condensation of acenaphthenequinone 1 and sarcosine 99 and L-prolin 96 with the dipolarophile (E)-3-arylidene-4-chromanones 159 (Schemes 65, 66) [78].

Scheme 65

Synthesis of novel dispiropyrrolizine derivatives

Scheme 66

Synthesis of novel dispiro compound

A facile regio- and stereoselective synthesis of novel dispiroheterocyclic hybrids was developed by reaction of benzo[1,4]oxazine/benzo[1,4]thiazine 162 and acenaphthoquinone 1, α-amino acids 96, 99 via 1,3-dipolar cycloaddition reaction and using 2,2,2-trifluoroethanol as a new alternative and non-nucleophilic solvent for rapid access to construct a diversity-oriented library of regioselectivity dispiropyrrolidine/thiapyrrolizidines 163, 164 were prepared (Scheme 67) [79].

Scheme 67

Synthesis of acenaphthaquinone containing benzo[1,4]thiazine/oxazine based dispiroheterocycles via azomethine ylides

Perumal and Thennarasu have developed the regioselective synthesis of a series of novel dispiropyrrolidines 166 through intermolecular 1,3-dipolar cycloaddition of azomethine ylides obtained from 1,2-diones like isatin 140 and sarcosine 99 with acenaphthenone-2-ylidine ketone 165 dipolarophiles in methanol under reflux conditions (Scheme 68) [80].

Scheme 68

Synthesis of novel dispiropyrrolidines

Perumal et al. has reported the reaction of isatin derivatives 140 and acenaphthenequinone 1 with α-amino acids 96 or 99, and acenaphthenone-2-ylidine ketone 165 dipolarophiles in methanol at reflux conditions that led to synthesis of a series of novel dispiropyrrolizidines 167, 168 (Scheme 69) [80].

Scheme 69

Synthesis of novel dispiropyrrolizidines

Li and coworkers in 2008 developed a novel method for the synthesis of dispiropyrrolidine derivatives 169 by a tandem Knoevenagel-1,3-dipolar cycloaddition reaction sequence of acenaphthylene-1,2-dione 1, sarcosine 99, 1,3-indanedione 24, and an aldehyde 81 without any catalyst and solvent-free (Scheme 70) [81].

Scheme 70

Synthesis of dispiropyrrolidine derivatives

As shown in Scheme 71, this research group evaluated the synthesis of glyco dispiro pyrrolizidines 173, 174 1,3-dipolar cycloaddition reaction. The novel glycosyl dipolarophile derived 172 from dicyclohexylidine glucose underwent neat [3 + 2] cycloaddition reaction with the azomethine ylide generated from 1,2-diketones 1 and cyclic amino acid 96, 121 to give the corresponding glycosidic heterocycles in good yields (Scheme 71) [82].

Scheme 71

Synthesis of a new dispiro pyrrolizidines

In 2013, synthesis of a series of novel dispiro pyrrolizidines 176 has been achieved by 1,3-dipolar cycloaddition reaction of azomethine ylide generated from secondary amino acids 96 and diketones 1 with bischalcones 175 (Scheme 72) [83].

Scheme 72

Synthesis of dispiro pyrrolizidines

29 Synthesis of Dispirooxindole-pyrrolidine/Pyrrolizidine Derivatives

Dandia et al., reaction of the 1,3-dipolar cycloaddition of 2-oxo-(2H)-acenaphthylen-1-ylidene-malononitrile 1 as dipolarophiles have been investigated for the first time with the azomethine ylides generated in situ from N-substituted isatin 140 and sarcosine 99 to furnish novel dispiro heterocycles 177 (Scheme 73) [84].

Scheme 73

Synthesis of dispiropyrrolidine oxindoles

Perumal’s group synthesized an efficient novel dispirooxindole-pyrrolidine derivative 180 through 1,3-dipolar cycloaddition of an azomethine ylide generated from acenaphthenequinone 1 and sarcosine 99 with the dipolarophile 3-(1H-indol-3-yl)-3-oxo-2-(2-oxoindolin-3ylidene)propanenitrile 179 in the absence of catalyst and in EtOH at reflux condition (Scheme 74) [85].

Scheme 74

Synthesis of spirooxindole derivatives

Bharitkar and coworker reported the facile, atomeconomic synthesis of novel spiro-pyrrolizidino-oxindole 182 adducts of withaferin-A 181 via the intermolecular cycloaddition of azomethine ylides generated in situ from l-proline 96 and acenaphthoquinone 1 withaferin-A (WA) has attracted the attention of chemists as well as biologists due to its interesting structure and various bio-activities (Scheme 75) [86].

Scheme 75

Synthesis of novel spiro-pyrrolizidino-acenaphthoquino withaferin-A

In 2007, Raghunathan et al. reported an efficient microwave-assisted ZrOCl₂·8H₂O-mediated synthesis of novel dispiro-oxindolopyrrolidines/pyrrolizidines 184 and 185 through [3 + 2] cycloaddition reaction of azomethine ylides derived from acenaphthenequinone 1 and sarcosine/l-proline 96, 99 with (E)-2-oxoindolino-3-ylidene acetophenones 183 as dipolarophiles in good yields (Scheme 76) [87].

Scheme 76

Synthesis of novel dispiro-oxindolopyrrolidines and -pyrrolizidines

30 Synthesis of Tetraspiro-bispyrrolidines and Tetraspiro-bisoxindolopyrrolidines

Raghunathan and Rajesh has reported an efficient approach to the synthesis of a new class of tetraspiro-bispyrrolidines and tetraspiro-bisoxindolopyrrolidines 187, 188 through 1,3-dipolar cycloaddition reaction and under solvent-free microwave conditions (Scheme 77) [88].

Scheme 77

Synthesis of tetraspiro-bispyrrolidines and tetraspiro-bisoxindolopyrrolidines

31 Synthesis of Spiro-pyrido-pyrrolizines and Pyrrolidines

In 2008, Kumar et al. reported the 1,3-dipolar cycloaddition of azomethine ylides derived from acenaphthenequinone 1 and α-amino acids viz. proline 96, phenylglycine 190 and sarcosine 99 to a series of 1-methyl-3,5-bis[(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones 189 for synthesis of novel spiro-pyrido-pyrrolizines and pyrrolidines 191, 192, 193 in quantitative yields (Scheme 78) [89].

Scheme 78

Synthesis of novel spiro-pyrido-pyrrolizines and pyrrolidines

32 Synthesis of Spiro Pyrrolidine-grafted Macrocycles

In 2013, Raghunathan accomplished the synthesis of 13- and 16-membered macrocyclic enone 196, 197, 198 with alkyl ether and triazole as a linker using intramolecular aldol condensation. The newly synthesized macrocyclic enone was successfully utilized as a dipolarophile in 1,3-dipolar cycloaddition. The dipole generated from acenaphthenequinone 1 with various secondary amino acids (sarcosine, l-proline, and thiazolidine-4-carboxylic acid) 96, 99 were reacted with macrocyclic enone 194, 195 to give a new class of spiropyrrolidine-grafted macrocycles 196, 197, 198 in good yield (> 85%) (Scheme 79) [90].

Scheme 79

Synthesis of spiroacenaphthenone pyrrolidine-grafted macrocycles

33 Synthesis of Dispiro-pyrrolo-thiazole

An efficient synthesis of spiroacenaphthene1″-one spiro[-arylmethylidene-1′-methylpiperidin-4′-one-7-aryltetrahydro-1H-pyrrolo[1,2-c][1,3]thiazoles 199 and spiroacenaphthene-1″-one spiro-arylmethylidene-1′-methylpiperidin-4′- one-4-aryloctahydroindolizines 200 was developed by reaction of 1,3-dipolar cycloaddition of azomethine ylides generated in situ from acenaphthenequinone 1 and α-amino acids 96, 121 viz. 1,3-thiazolone-4-carboxylic acid and piperidine-2-carboxylic acid to a series of 1-methyl-3,5-bis[(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones 189 in good yield (Scheme 80) [91].

Scheme 80

Synthesis of dispiroacenaphthene

34 Synthesis of Polycyclic Hybrid Heterocycles

The synthesis of polycyclic hybrid heterocycles 202, 203 by utilizing a 1,3-dipolar cycloaddition of azomethine ylides, generated in situ via decarboxylative condensation of acenaphthoquinone 1 and N-substituted sarcosine/thiazolidine-4-carboxylic acid 96, 99 with 2-[arylmethylidene]-3,4-dihydro-1(2H)-acridinones 201 in a three-component fashion was reported by Perumal and coworkers (Scheme 81) [92]. The reaction, via initial formation of azomethine ylide 206, generated by the condensation of sarcosine 99 and acenaphthoquinone 1 followed by decarboxylation. Concomitant cycloaddition of the azomethine ylide 206 to 2-[arylmethylidene]-3,4-dihydro-1(2H)-acridinones 207 affords the cycloadducts 204, which undergose intramolecular via the reaction of the methylene group of the carbocyclic ketone fused to the quinoline moiety with the remaining acenaphthoquinone carbonyl of 204 furnishes 205 (Scheme 82).

Scheme 81

Synthesis of polycyclic hybrid heterocycles

Scheme 82

Plausible mechanism for the formation of polycyclic hybrid heterocycles 159

35 Synthesis of Dispiro-acenaphthen-pyrroloisoquinoline

The dipolarophiles 2-arylidene-indanediones 208 can be easily obtained via a two-component condensation of indandione with various benzaldehydes. The reaction of tetrahydroisoquinoline-3-carboxylic acid 122 with acenaphthenequinone 1 under different conditions to give an azomethine ylide. The ylide intermediate undergoes a 1,3-dipolar cycloaddition with 2-arylidene-indanediones 208 in a one-pot, three-component reaction led to the formation hexahydro-1-phenyl-spiro[2.2′]-indane-1,3-dione-spiro[3.2″]acenaphthen-1-one-pyrrolo[1,2-a]isoquinoline 209. This group carried out this reaction using different methods: silica, BiCl₃–silica or TiO₂–silica under MW irradiation. The best results were obtained by the last method (TiO₂–silica). TiO₂–silica is used as an efficient solid-supported catalyst (Scheme 83) [93].

Scheme 83

Synthesis of dispiroheterocyclic

In 2014, Yan et al. described the synthesis of 2′-acenaphthylidenespiro[indane-2,1′-pyrrolo[2,1-a]isoquinolines] 211 were efficiently synthesized by three-component reactions of in situ-generated N-phenacylisoquinolinium bromides 210 with indane-1,3-dione 24 and acenaphthoquinone 1 in ethanol using triethylamine as the base (Scheme 84) [94].

Scheme 84

Synthesis of 2′-acenaphthylidenespiro[indane-2,1′-pyrrolo[2,1-a]isoquinolines]

36 Synthesis of Acenaphthylene Dispiro Heterocycles

Synthesis of novel acenaphthylene dispiro heterocycles 213, 214, 215, 216 has been achieved by a one-pot, three-component 1,3-dipolar cycloaddition reaction. The azomethine ylides generated in situ from N-substituted acenaphthoquinone 1 and α-amino acids 96, 99, 190 viz. sarcosine, phenylglycine, 1,3-thiazolane-4-carboxylic acid and proline reacted with 2,6-bis[(E) arylmethylidene] cyclohexanones 212 as a dipolarophile to give acenaphthylene dispiro heterocycles in quantitative yields (Scheme 85) [95].

Scheme 85

Synthesis of spiro-cyclohexanones

37 Synthesis of Acenaphtho[1,2-b]quinoxaline Derivatives and Acenaphtho[1,2-b]pyrazine

The reaction of acenaphthoquinone 1 with diamines 217, 219 in phenol afforded the synthesis of acenaphtho[1,2-b]quinoxaline 218 and acenaphtho[1,2-b]pyrazine 220 (Scheme 86) [96].

Scheme 86

Synthesis of acenaphtho[1,2-b]quinoxaline 218 and acenaphtho[1,2-b]pyrazine 220

In 2014, an efficient synthesis of quinoxaline scaffolds 221 was developed by reaction of acenaphthoquinone 1 with diamines 128 under solid-state melt reaction (SSMR) with excellent yields (Scheme 87) [97].

Scheme 87

Synthesis of quinoxaline

Shirini et al. synthesized quinoxaline derivatives 222 in a mixture of H₂O and CH₃CN at 50 °C and in the presence of rice husk (RiH) with excellent yields with acenaphthoquinone 1 and diamines 128 (Scheme 88) [98].

Scheme 88

Synthesis of quinoxaline

38 Synthesis of Spiroisoindoline-1,2′-quinazoline

Shekouhy et al. suggested an efficient synthesis of 1-H-spiro[isoindoline-1,2′-quinazoline]-3,4′(3′H)-diones 224 via the reaction of acenaphthoquinone 1 with 2-aminobenzamide 223 in H₂O using of zirconium tetrakis(dodecyl-sulfate) [Zr(DS)₄] at room temperature (Scheme 89) [99].

Scheme 89

Synthesis of quinazoline derivatives

One-pot reaction of 2-nitrobenzamides 225 and acenaphthoquinone 1 in the presence of a catalytic amount of SnCl₂·2H₂O and in EtOH as solvent gave 10H-spiro[indoline-3,2′-quinazoline]-2,4′(3′H)-dione derivatives 226 in good yield (Scheme 90) [100].

Scheme 90

Synthesis of 10-H-spiro[indoline-3,2′-quinazoline]-2,4′(3′H)-dione derivatives

The synthesized 1-H-spiro[isoindoline-1,2′-quinazoline]-3,4′(3′H)-diones 227 by Pore and coworkers via the reaction of acenaphthoquinone 1 with 2-aminobenzamide 223 in EtOH in the presence of Solfamic acid at room temperature (Scheme 91) [101]. A plausible mechanism for the reaction is shown in Scheme 92. At beginning, acenaphthoquinone 1 was activated by sulfamic acid, then the carbonyl unit of the acenaphthoquinone 1 undergoes nucleophilic attack by amine of anthranilamide 223 to afford an imine intermediate 228, which undergoes intramolecular cyclization involving nucleophilic attack by –CONH₂ moiety on –C=N– was obtain the corresponding product 227(Scheme 92).

Scheme 91

Synthesis of spiro[isoindoline-1,2′-quinazoline]-diones

Scheme 92

Plausible mechanism for the synthesis of 1-H-spiro [isoindoline-1,2-quinazoline]-3,4 (3H)-diones

39 Synthesis of Dihydroacenaphtho[1,2-b]pyrazine/Pyridopyrazine

The reaction of acenaphthoquinone 1 with diamines 219, 229, 231 in the presence of catalyst Pd/SBA-15 as nanocatalyst to afford synthesis of dihydroacenaphtho[1,2-b]pyrazine 220 and acenaphtho[1,2-b]pyrido[2,3-e]pyrazine 230 and acenaphtho[1,2-b]pyrido[3,4-b]pyrazine 232 heterocycles with good to excellent yields under green conditions (Scheme 93) [102].

Scheme 93

Synthesis of dihydroacenaphtho[1,2-b]pyrazine 172 and acenaphtho[1,2-b]pyrido-pyrazine 181, 183

40 Synthesis of Spiro[benzo[c]pyrano[3,2-a]phenazine] Derivatives

Hasaninejad and coworkers prepared a novel multicomponent reaction for the synthesis of spiro[benzo [c]pyrano[3,2-a]phenazine] derivatives 235 by acenaphthoquinone 1, activated methylene reagent 7, 2-hydroxy-1,4-naphthoquinone 233 with aromatic 1,2-diamines 234 in the presence of l-proline (30 mol%) as a bifunctional organocatalyst in EtOH under reflux conditions (Scheme 94) [103].

Scheme 94

One-pot, four-component synthesis of novel spiro[benzo[c]pyrano[3,2-a]phenazine] derivatives

41 Synthesis of Spiroacridine Derivatives

Spiroacridine 236 were prepared from the reaction of acenaphthoquinone 1, dimedone 63a, and ammonium hydroxide 31 in the presence of FeNi₃–SiO₂ as the nanocatalyst at room temperature in water is reported (Scheme 95) [104].

Scheme 95

Synthesis of spiroacridine

An efficient synthesis of 9-spiroacridine derivatives 237 was developed by reaction of enaminones 60 and acenaphthoquinone 1 in CH₃CN in the presence of para-toluenesulfonic acid in good yield by Chen’s group (Scheme 96) [105]. A plausible mechanism is shown in Scheme 97. The first step, the aza-ene addition of enaminone 60 to acenaphthoquinone 1, leads to intermediate 238, which undergoes a rapid imine–enamine tautomerization to give intermediate 239. Afterwards, intermediate 239 accepts one proton to form 240, and the elimination of H₂O from intermediate 240 gives iminium ion 241 enaminone 60 then in a Michael addition with compound 241 to afford intermediate 242, the –NH group of which under an intramolecular attack of the carbonyl group, resulting in a cyclization reaction that to form 243. Finally, intermediate 243 loses a molecule of water to lead to the formation of acridine 237 (Scheme 97).

Scheme 96

Synthesis of 9-spiroacridine derivatives

Scheme 97

Proposed mechanism for the synthesis of spiroacridines

The combination of acenaphthoquinone 1, an activated methylene reagent 244, and 1,3-dicarbonyl compounds 63 in the presence of catalytic ammonium chloride was found to be a suitable and efficient method for the synthesis of the spiro acenaphthylene 236 (Scheme 98) [106].

Scheme 98

Synthesis of spiroacridine

42 Synthesis of Spiro Chromeno-pyrimidine

The spiro acenaphthylene derivative 245 was obtained by reaction of acenaphthoquinone 1, cyclohexane-1,3-diones 63 and barbituric acids 68 in H₂O containing a catalytic amount of dodecyl benzenesulfonic acid functionalized silica-coated magnetic nanoparticles (γ-Fe₂O₃@SiO₂-DDBSA) at reflux temperature (Scheme 99) [107].

Scheme 99

Spiro[acenaphthylene-1,5-chromeno[2,3-d]pyrimidine] derivatives

In 2010, Jadidi and coworkers reported an efficient one-pot synthesis of novel synthesis of spiro[acenaphthylene-1,5′-chromeno[2,3-d]pyrimidine] derivatives 246 by a three-component condensation reaction of barbituric acids 68 and acenaphthoquinone 1 with 5,5-dimethyl-cyclohexane-1,3-dione 63a refluxing water in the presence of p-TSA for 10 h (Scheme 100) [108].

Scheme 100

Synthesis of spiro[acenaphthylene-1,5′-chromeno[2,3-d]pyrimidine] derivatives

43 Synthesis of Spirochromene-spiropyran-spiropyranopyrazole

In 2014, Azizi and coworkers reported a simple and efficient synthesis of spiro acenaphthylene 247 by one-pot, three-component reaction of acenaphthoquinone 1, malononitrile 7 and different nucleophiles 63a in biodegradable choline chloride-based deep eutectic solvent in good yields 50–95% (Scheme 101) [109].

Scheme 101

One-pot, three-component synthesis of spiro acenaphthylene in DES

A green and efficient method for the synthesis of various spirochromenes 249 is reported by one-pot, three-component domino reaction of acenaphthoquinone 1, malononitrile 7 and 1, 3-dicrbonyl compounds 63(a, b) in the presence of FeNi₃–SiO₂ as the nano-catalyst at room temperature in water with high-product yields (Scheme 102) [104].

Scheme 102

Synthesis of spirochromene derivatives

Synthesis of new spirochromene derivatives 249, 250 by an organo-catalyzed via one-pot three-component condensation reaction of acenaphthoquinone 1, active methylene compounds 7 and cyclic 1,3-diketones/4-hydroxycoumarin 63(a-c), 248 in refluxing PEG 400 in the presence of Gold(III) chloride (HAuCl₄·3H₂O) was reported by Kidwai et al. (Schemes 103, 104) [110].

Scheme 103

Synthesis of spirochromene derivatives

Scheme 104

Synthesis of spiroacenaphthylene derivatives

The combination of acenaphthoquinone 1, an activated methylene reagent 7, and 1,3-dicarbonyl compounds 63 in the presence of catalytic ammonium chloride was found to be a suitable and efficient method for the synthesis of the spiro acenaphthylene 247 (Scheme 105) [106].

Scheme 105

Synthesis of spirochroman

Reaction of compound 1 with malononitrile 7 and α-methylenecarbonyl compounds (β-diketones, pyrazolones) in the presence of (benzyl)(dimethyl)(N,N-dimethylaminoethyl) ammonium chloride as the basic ionic liquid an efficient and reusable catalyst for the synthesis of spiro acenaphthylenes 252 in water (Scheme 106) [111].

Scheme 106

One-pot synthesis of the spiroacenaphthylene derivatives

Elinson and coworkers condensed acenaphthoquinone 1 with a number of cyclic CH-acids in ROH/water at 80 °C with 90–95% yields. Then malononitrile 7 was added to form spiro acenaphthylene heterocycles 253. Thus, a new simple and efficient green ‘one-pot’ method to synthesize substituted spiroacenaphthylene frameworks was found directly from simple starting compounds. The application of this convenient green multicomponent method is also beneficial from the viewpoint of diversity-oriented large-scale processes (Scheme 107) [112]. In the proposed mechanism for this reaction, the Michael addition of cyclic CH-acid 63a to the Knoevenagel adduct 14 followed by intramolecular cyclization leads to the desired spiroacenaphthylene 253 (Scheme 108).

Scheme 107

Synthesis of spiro[acenaphthylene-1,4-pyrano [3,2-c]chromene]-3-carbonitrile

Scheme 108

Plausible mechanism for the synthesis of spiro acenaphthylene heterocycles

Heravi et al. have described the one-pot, three-component synthesis of the spiro acenaphthylene derivatives 259 via the reaction of acenaphthoquinone 1, malononitrile/ethylcyanoacetate 7, and various reagents including α-methylencarbonyl compounds/enols in EtOH and Et₃N as catalyst (Scheme 109) [113]. A plausible mechanism of the reaction is proposed in Scheme 110. Compound 1 undergoes Knoevenagel condensation with malononitrile/ethylcyanoacetate and leads to the formation 14. Reactant 63a with Michael addition to reagent 14 is followed by cycloaddition on to the nitrile. Finally, after tautomeric proton shift, the corresponding products 260 is formed (Scheme 110).

Scheme 109

One-pot, three-component synthesis of the spiroacenaphthylene derivatives

Scheme 110

Plausible mechanism for the synthesis of spiro acenaphthylene heterocycles

Spiro[acenaphthyl-3,4′-pyrano[2,3-c]pyrazole] derivatives 262 were prepared from the reaction of hydrated hydrazine 261, dimethyl acetylenedicarboxylate 18, acenaphthenequinone 1 and malononitrile or ethyl cycanoacetate 7 in ethanol in the presence of triethylamine with good yields (Scheme 111) [114]. A sequential reaction mechanism is proposed for this four-component reaction based on the previous reported synthetic reactions of Huisgen’s 1,4-dipoles and the spiro[indoline-3,4′-pyrano[2,3-c]pyrazole]. Firstly, the addition of hydrazine to acetylenedicarboxylate forms the 2-hydrazinyl substituted but-2-enedioate 263. Secondly, the intramolecular hydrazinolysis of one ester affords a pyrazolone intermediate 264, which in turn was deprotonated by triethylamine to transform a carbanium ion 265. In the meantime, the triethylamine-catalyzed condensation of acenaphthoquinone with malononitrile produces the 2-(2-oxoacenaphthylen-1(2H)-ylidene)malononitrile 266. Thirdly, a Michael addition of the carbanium ion 265 to component 266 gives the adduct 267. Then, the adduct 267 transforms to a emulate 268 through the keto-enol tautomerization. Finally, the intramolecular addition of enolate to the cyano group results in the obtained spiro[acenaphthyl-3,4′-pyrano[2,3-c]pyrazole] derivatives 262 with an imine-enamine tautomerization (Scheme 112).

Scheme 111

Four-component reaction for synthesis of spiro[acenaphthyl-3,4′-pyrano[2,3-c]pyrazoles]

Scheme 112

Plausible mechanism for the synthesis of component 262

A one-pot, three-component reaction has been reported for the synthesis of spiro-pyran derivatives 269 with acenaphthenequinone 1, malononitrile 7, and 1,3-dicarbonyl compounds such as cyclohexane-1,3-dione, dimedone, and barbituric acid in ethanol with NaHCO₃ as the catalyst. (Scheme 113) [115]. A proposed mechanism for the synthesis of component 269 is shown in Scheme 114.

Scheme 113

Synthesis of spiro-pyran derivatives

Scheme 114

Proposed mechanism for the synthesis of 269

A series of new spiro[4H-pyran] derivatives 271 were obtained by one-pot, three-component domino reaction of acenaphthoquinone 1, malononitrile 7, and different reagents including 1, 3-dicrbonyl compounds, β-naphthol and 4-hydroxycumarin the presence of nano SiO₂ at 90 °C temperature, solvent-free without any prior activation or modifications (Scheme 115) [116].

Scheme 115

Synthesis of spiroacenaphthylenes derivatives

In 2013, Saluja’s group developed an efficient synthesis of biologically and pharmacologically important spiropyrans derivatives 272 from condensation of malononitrile/ethyl cyanoacetate 7, 1,3-dicarbonyl compounds, and acenaphthoquinone 1 in water using 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as catalyst in good yields (Scheme 116) [117].

Scheme 116

Synthesis of spiroacenaphthylenes derivatives

Refluxing of acenaphthoquinone 1, an activated methylene reagent 7, and 1,3-dicarbonyl compounds 63a in the presence of catalytic silica bonded N-propyl sulfamic acid (SBNPSA) in ethanol under irradiation microwave conditions was found to be a suitable and efficient method for the synthesis of the biologically important spiropyran 273 (Scheme 117) [118].

Scheme 117

Synthesis of spiropyran

The multicomponent efficient synthesis of biologically active spiro-4H-pyran derivatives 271 was successfully developed by the three-component reaction of acenaphthoquinone 1, malononitrile 7, and various reagents including α-methylencarbonyl compounds/enols in the presence of a catalytic amount of copper(II) acetate monohydrate with good yields (Scheme 118) [119].

Scheme 118

Synthesis of biologically active spiro-4H-pyran derivatives

A convenient and efficient synthesis of biologically and pharmacologically important spiro-pyrans 274 from the condensation of malononitrile 7, 1,3-dicarbonyl compounds, and acenaphthoquinone 1 has been reported using recyclable heterogeneous polyethylene glycol (PEG)-stabilized Ni nanoparticles in ethylene glycol (Scheme 119) [120].

Scheme 119

Synthesis of biologically and pharmacologically important spiro-pyrans

Reaction of acenaphthenequinone 1, activated methylene reagent 7, and 1,3-dicarbonyl compounds in the presence of Isinglass (IG) as a biopolymer has considerable catalytic efficiency for the synthesis of biologically important functionalized spiroacenaphthylenes 275 in water (Scheme 120) [121].

Scheme 120

Synthesis of spiroacenaphthylenes

Shirini et al. have described the one-pot, three-component synthesis of the spiro acenaphthylene derivatives 276 via the reaction of acenaphthoquinone 1, malononitrile 7, and various reagents including α-methylencarbonyl compounds/enols in water and using C₄(DABCO-SO₃H)₂·4Cl as a nano, efficient, cheap, and reusable catalyst under mild and homogeneous conditions. (Scheme 121) [122].

Scheme 121

Synthesis of spiro acenaphthylene derivatives

44 Synthesis of Spiro-tetrahydropyrazolopyridine Derivatives

Dabiri et al. conducted a catalyst-free, one-pot, 2A + 2B + C + D four-component process employing 1,3-dicarbonyl compound 32, an acenaphthoquinone 1, hydrazine 261 and ammonium acetate 277 in ethanol as a green media for the synthesis of some tetrahydropyrazolopyridine derivatives 278 (Scheme 122) [123].

Scheme 122

Synthesis of tetrahydropyrazolopyridine derivatives

45 Synthesis of Spiroacenaphthyleneindeno-pyrazolo-pyridine]dione

In 2011, Bazgir et al. reported the synthesis of spiro[acenaphthylene-indeno[1,2-b]pyrazolo[4,3-e]pyridine]diones 280 by the three-component reaction of 1,3-indandione 24, pyrazol-5-amines 279 and acenaphthylene-1,2-dione 1 in ethanol at reflux (Scheme 123) [124].

Scheme 123

Synthesis of spiro[acenaphthylene-1,4′-indeno[1,2-b]pyrazolo[4,3-e]pyridine]-dione

46 Synthesis of Triazolo[1,2-a]indazole-trione Derivatives

Hasaninejad et al. discovered the synthesis of triazolo[1,2-a]indazole-triones 282 by the condensation reaction between dimedone 63a, acenaphthoquinone 1, and ueazoles 281 in the presence of a catalytic amount of sulfonated polyethylene glycol (PEG-SO₃H) under solvent-free conditions at 80 °C. That as a highly stable and reusable eco-friendly degradable polymeric catalyst is described (Scheme 124) [125].

Scheme 124

Synthesis of triazolo[1,2-a]indazole-triones

47 Synthesis of Spiro Pyridodipyrimidines

In 2008, Mohammadizadeh et al. reported that spiro pyridodipyrimidines 284 could react with acenaphthoquinone 1, 1,3-dimethyl-6-aminouracil 283 under classical or microwave-assisted solvent-free conditions in good yields (Scheme 125) [126]. Mechanistic representation for synthesis of spiro pyridodipyrimidines 284 was shown in Scheme 126.

Scheme 125

Synthesis of spiro pyridodipyrimidines

Scheme 126

Mechanistic representation for synthesis of spiro pyridodipyrimidines

48 Synthesis of Pyrimido-azocine Derivatives

In 2014, Mohammadizadeh et al. reported the synthesis of new naphtho[1,8-ef]pyrimido[4,5-b]azocine-7,10,12,13(8H,9H,11H)-tetraones 287 by the addition reaction of acenaphthoquinone 1 and 6-aminouracil derivatives 283 in the presence of lead(IV) acetate at room temperature/in EtOH at room temperature (Scheme 127) [127].

Scheme 127

Synthesis of azocine derivatives

49 Synthesis of Spiro-indeno-pyrido-pyrimidines

Bazgir et al. described the synthesis of spiroacenaphthylene-1,4′-indeno-1,5′-pyrido[2,3-d]pyrimidines 288 under reflux in ethanol and catalyst-free by the three-component reaction of acenaphthylene-1,2-dione 1, 1,3-indandione 24, amino uracils 283(a–d) (Scheme 128) [128].

Scheme 128

Synthesis of spiroacenaphthylene-1,4′-indeno-1,5′-pyrido[2,3-d]pyrimidines

50 Synthesis of Spiro-indeno-benzoquinoline

Rad-Moghadam’s researcher group established a novel synthesis of spiro[1H-indeno[1,2-b]benzo[f]quinolin-13,1′(20H)- acenaphthylene]-7,13-dihydro-12,2′-dione 290 expediently through three-component reactions between 2H-indene-1,3-dione 24, 2-naphthalenamine 289 and acenaphthylene-1,2-dione 1 under catalysis of the ionic liquid N,N,N,N- tetramethylguanidinium triflate/H₂O–EtOH (5:1), p-TSA, 60 °C (Scheme 129) [129, 130].

Scheme 129

Synthesis of spiro[1H-indeno[1,2-b]benzo[f]quinolin-13,1′(2′H)- acenaphthylene]-7,13-dihydro-12,2′-dione

The first step may involve a Knoevenagel condensation between the 2H-indene-1,3-dione 24 and acenaphthoquinone 1 for the formation of the stable intermediate 291, which Michael addition of naphthalen-2-amine 289 followed by cyclocondensation of the resultant adducts 292 give the corresponding products 290 (pathway A). Alternatively, the key intermediates 291 may be produced by condensation of 2H-indene-1,3-dione 24 with the preformed imine derived from the reaction between acenaphthoquinone 1 and naphthalen-2-amine 289 (pathway B) (Scheme 130).

Scheme 130

Proposed mechanism for the formation of compound 290

51 Synthesis of Spiro-benzo-pyrazoloquinoline

In 2012, Bazgir et al. developed a convenient synthesis of spiro[acenaphthylene-1(2H),11′-[11H]-benzo[g]pyrazolo[4,3-b]quinoline]-2,5′,1″-triones 293 by a three-component condensation reaction of 2-hydroxy-1,4-naphthoquinone 233, pyrazol-5-amines 279, and acenaphthylene-1,2-dione 1 in the presence of p-TSA as an inexpensive and available catalyst in refluxing ethanol (Scheme 131) [131].

Scheme 131

Synthesis of spiro[acenaphthylenebenzopyrazolo quinoline]triones

52 Synthesis of Dihydroacenaphthylen-indene-dione

Bazgir et al. described the synthesis of 2-(1-(4-(dimethylamino)phenyl)-2-oxo-1,2-dihydroacenaphthylen-1-yl)-1H-indene-1,3(2H)-dione 295 as new unsymmetrical oxindoles via a Friedel–Crafts-type three-component reaction of acenaphthoquinone 1, 1,3-indandion 24, N,N-dimethylaniline 294 in ethanol in the presence of LiClO₄ (Scheme 132) [132].

Scheme 132

Synthesis of 2-oxo-1,2-dihydroacenaphthylen-1-yl)-1H indene-dione

53 Synthesis of Spiroxindole

Nandakumar’s group has accomplished a concise and efficient route for the synthesis of highly substituted spiroxindole derivatives from acenaphthenequinone precursor 297 by a reaction mixture of acenaphthoquinone 1, malononitrile 7, and 3-cyanoacetyl indole 296 and triethyl amine (20 mol%) in methanol under ambient temperature (Scheme 133) [133].

Scheme 133

Synthesis of spiroxindole derivatives from acenapthenequinone precursor

A plausible mechanism is propose. At beginning, acenaphthoquinone 1 reacts with malononitrile 301 to give a 2-(2-oxoacenaphthylen-1(2H)-ylidene)malononitrile adduct 14 and 3-cyanoacetyl indole 296 in the presence of base (Et₃N) enolise to give 298; 298 further reacts with 14 to give intermediates 299 and 300. The intermediate further rearranges via proton transfer to give 301. Finally, the intermediate 301 affords to yield a spiroxindole derivative from acenaphthenequinone precursor 297 via proton transfer (Scheme 134).

Scheme 134

Proposed mechanism for the synthesis of 297

54 Synthesis of Dispiro Dihydrofuranyl Acenaphthyl Oxindole Derivatives

Perumal’s group developed an efficient synthesis of dispiro dihydrofuranyl acenaphthyl oxindole derivatives 303 via reaction between spirolactones 302 and acenaphthoquinone 1 catalyzed by Et₃N (triethylamine) in reflux MeOH. Also, spirolactones 302 from isatin 140, primary amines 17, and DMAD 18 through Huisgen dipolar additions are discussed (Scheme 135) [134]. A plausible mechanism of the reaction is proposed in Scheme 67. Initially, m-toluidine 17 adds on to DMAD 18 to provide the zwitterionic intermediate 304, which adds on to isatin 140 to form 305 and then undergoes intramolecular addition with MeOH elimination to give the spiro lactone 302, then adds on to acenaphthoquinone 1 to form 303) Scheme 136).

Scheme 135

Synthesis of dispirodihydrofuranyl oxindoles

Scheme 136

Plausible mechanism for the formation of 228

55 Synthesis of Spiro-pyrrolo-pyridine Derivatives

As shown in Scheme 137, Langer’s research group in 2013 established a three-component reaction of acenaphthoquinone 1, N-substituted 5-amino-3-cyanopyrroles 307 and active methylene compounds 308, 309, and 248 under mild conditions using ethanol, acetic acid, or 1,4-dioxane as solvent for the synthesis of 4,7-dihydro-spiro1H-pyrrolo[2,3-b]pyridines 312 (Scheme 137) [135].

Scheme 137

Synthesis of 4,7-dihydro-1H-pyrrolo[2,3-b]pyridines

56 Sythesis of Spiro Acenaphthylene

Elinson and coworkers discovered that cyclic ketones 313, 315, and two molecules of malononitrile reacted with acenaphthylene-1,2-dione 1 to afford spiro acenaphthylene pentacyclic and pentaheterocyclic 314, 316 in 70–95% yields (Schemes 138, 139) [136].

Scheme 138

Synthesis of spiroacenaphthylene derivatives

Scheme 139

Synthesis of spiroacenaphthylene pentacyclic systems

The first step may involve a Knoevenagel condensation between the malononitrile and acenaphthenequinone 1 for the formation of the Knoevenagel adduct 14 in base condition. A similar Knoevenagel condensation of cyclohexanone and malononitrile anion lead to Knoevenagel adduct 317. Under basic conditions, Knoevenagel adduct 317 forms anion 318, which adds to the activated double bond of Knoevenagel adduct 14 with further cyclization into anion 320. Finally, after tautomeric proton shift, compound spiroacenaphthylene 314 is formed (Scheme 140).

Scheme 140

Proposed mechanism for the synthesis of 233

57 Synthesis of Spiroacenaphthylene Pyrazolo-chromene

Refluxing of hydrazine derivatives 261 with ethyl acetoacetate 32 by MgCl₂ in ethylene glycol afforded pyrazolinone derivative 321. Treatment of 321 with 2-hydroxy-1,4-naphthoquinone 233 and acenaphthoquinone 1 in ethylene glycol in the presence of MgCl₂ gave spiro acenaphthylene 322 (Scheme 141) [137].

Scheme 141

Synthesis of spiroacenaphthylene catalyzed by MgCl₂ in EG

58 Synthesis of 2,2-Diphenylacenaphthylen-1(2H)-one

In 2008, Klumpp et al. described the synthesis of 2,2-diphenylacenaphthylen-1(2H)-one 324. These compounds were obtained via the two-component reactions of acenaphthenequinone 1 with a series of arenes 323 in benzene using CF₃SO₃H (triflic acid) as catalyst in good yields 58–99% with high regioselectivity (Scheme 142) [138].

Scheme 142

Synthesis of 2,2-diphenylacenaphthylen-1(2H)-one

59 Synthesis of Acenaphthenequinonediimine Derivative

Ragaini et al. have reported the reaction of acenaphthoquinone 1 with amines 17 in methanol, at 60 °C, which gave alkyl-BIAN = bis(alkyl) acenaphthenequinonediimine derivative 325. Ragaini et al. have investigated the reason for earlier failures and identified it as an isomerization of the initially formed CQN double bond. This isomerization is driven by a release of ring strain in the five-membered ring of the acenaphthene moiety. The use of amines in which the –NH₂ group is bound to a quaternary carbon atom cannot be employed to avoid the isomerization because these amines are too sterically encumbered to react at all. However, the use of amines in which the amino group is bound to a strained ring solves the problem, because the isomerization would cause an even larger strain than the one that is released. Cyclopropylamine (Cypr-NH₂) is the ideal amine, with no isomerization being observed at all. The best synthetic procedure involves a trans imination reaction from a [ZnCl₂(Ar-BIAN)] complex, where Ar contains electron-withdrawing groups, but the direct synthesis from acenaphthenequinone and the amine is also possible in the case of Cypr-BIAN. (Scheme 143) [139].

Scheme 143

Synthesis of bis(alkyl)acenaphthenequinonediimine derivative

60 Synthesis of Oxoacenaphthylen-ylidene Semicarbazide/Ylidene Amino-isothiourea

Novel (Z)-1-(1-oxoacenaphthylen-2(1H)-ylidene)semicarbazide 327 and 1-(1-oxoacenaphthylen-2(1H)-ylidene amino)isothiourea 329 were synthesized via a two-component reaction of acenaphthoquinone 1 with hydrazinecarboxamide hydrochloride 326/hydrazinecarbothioamide hydrochloride 328 in EtOH at 90 °C for 5 h (Scheme 144) [140].

Scheme 144

Synthesis of oxoacenaphthylen-2(1H)-ylidene)semicarbazide/isothiourea

61 Synthesis of Diamine Acenaphtohydrazinomercaptotriazole

A diamine acenaphtohydrazinomercaptotriazole (AHTD) 331 was synthesized in one step from acenaphthoquinone 1 and 4-amino-3-hydrazino-5-mercapto-1,2,4-triazole 330 in EtOH and in the presence of concentrated HCl (Scheme 145) [141].

Scheme 145

Synthesis of acenaphtohydrazinomercaptotriazole

62 Synthesis of Spiro-aceanthrene-thiazolidine-dione Derivatives

Reaction of acenaphthenequinone 1 with diaminomaleonitrile 332 at reflux temperature gave acenaphtho[1,2-b]pyrazine-8,9-dicarbonitrile 333. The reaction of 333 with hydrazine hydrate 261 afforded the corresponding cyclic products, 8,11-diaminoacenatho[1,2-b]pyrazino[2,3-d]pyridazine 334. The reaction of 1 with p-bromoaniline in presence of ZnCl₂ afforded complexes bis(p-bromophenylimino)acenaphthene 337. Amer et al. have also described the synthesis of spiro[2H-aceanthrene-2,2′-thiazolidine]-1,4′-dione derivatives 336 (Scheme 146) [142].

Scheme 146

Reaction of acenaphthenequinone with various reagents

63 S_NAr^H Reactions

Li et al. have revisited the synthesis of a series of ICT fluorophores, which were reported to have a core structure of 8-oxo-8H-acenaphtho[1,2-b]pyrrol-9-carbonitrile. Their core structure was corrected as 1-oxo-1H-phenalene-2,3-dicarbonitrile 338. The oxidative S_NAr^H reaction of 338 with mercaptopropionic acid was very slow and less efficient. After refluxing in CH₃CN for 2 days, only a small fraction of 338 was converted to the product as a single regioisomer. Due to the strong electron-withdrawing groups on 338, its naphthalene ring shows a highly electron-deficient nature and oxidative S_NAr^H reactions can precede smoothly under very mild conditions. Several nucleophiles, such as thiols, hydroxide, and amines, were used for the structural modification of 338 (Scheme 147) [143].

Scheme 147

S_NAr^H reactions of 1 with different nucleophiles

64 Synthesis of Bis-1,4-dioxane

Reaction of acenaphthoquinone 1 with butane-2,3-diol 339 led to formation bis-1,4-dioxane (bis-ketal) 340 (Scheme 148) [144].

Scheme 148

Synthesis of bis-ketal

65 Synthesis of Acenaphtho[1,2-b]quinoxaline-Based Low-Band-Gap Polymer

Reaction of 341 with acenaphthoquinone 1 in acetic acid afforded compound 342 and reaction with Br₂ in CHCl₃ was developed acenaphtho[1,2-b]-quinoxaline 343. Compound 344 reacted with acenaphthoquinone 1 as a 1,2-dicarbonyl in the presence zinc dust and acetic acid to afford compound 345 and reaction with NBS in CHCl₃ was developed acenaphtho[1,2-b]-quinoxaline 346. Bis(trimethyltin) BDT monomer 347 and 343 or 346 were mixed in toluene and DMF. After being purged with nitrogen, Pd(PPh₃)₄ to be synthesized corresponding products (Scheme 149) [145].

Scheme 149

Synthesis of acenaphtho[1,2-b]-quinoxaline and polycondensation reaction

66 Synthesis of Bis-acenaphtho[1,2-b]quinoxaline

An efficient synthesis of 8,11-dibromoacenaphtho[1,2-b]quinoxaline 349 has been developed with the reaction of acenaphthoquinone 1 and 4,7-dibromobenzo[c][1,2,5]thiadiazole 348. The reaction of 352 with (2,3-dihydrothieno[3,4-b][1,4]dioxin-5-yl)trimethylstannane 350 led to formation 8,11-bis(2,3-dihydrothieno[3,4-b][1,4]dioxin-5-yl)acenaphtho[1,2-b]quinoxaline 351 (Scheme 150) [146].

Scheme 150

Synthesis of 8,11-bis(2,3-dihydrothieno[3,4-b][1,4]dioxin-5-yl)acenaphtho[1,2-b]quinoxaline

The synthesis of 3,6-dibromo-4,5-bis(octyloxy)benzene-1,2-diamine 353 with 4,7-dibromo-5,6-bis(octyloxy)benzo[c][1,2,5]thiadiazole and NaBH₄ in EtOH has been reported. Reaction of 4,7-dibromo-5,6-bis(octyloxy)benzo[c][1,2,5]thiadiazole with acenaphthoquinone 1 in the presence of catalyst AcOH in reflux CH₃CN to afford synthesis of 8,11-dibromo-9,10 bis(octyloxy)acenaphtho[1,2-b]quinoxaline 354. Reaction of 354 with 2-(4-dodecylthiophen-2-yl)-5,5-dimethyl-1,3,2-dioxaborinane 355 in the presence of Pd(PPh₃)₄ in toluene at 90 °C for synthesis of 8,11-bis(4-dodecylthiophen-2-yl)-9,10-bis(octyloxy)acenaphtho[1,2-b]quinoxaline 356. A solution of N-bromosuccimide (NBS) in DMF was added to 356 for synthesis of 8,11-bis(5-bromo-4-dodecylthiophen-2-yl)-9,10-bis(octyloxy)acenaphtho[1,2-b]quinoxaline 357 (Scheme 151) [147].

Scheme 151

Synthesis of 8,11-bis(5-bromo-4-dodecylthiophen-2-yl)-9,10-dioctyloxyacenaphtho[1,2-b]quinoxaline

67 Diimine Cu(I) Complex with Acenaphthoquinone

A novel diimine Cu(I) complex [Cu(ABPQ)(DPEphos)]BF₄ [ABPQ and DPEphos are acenaphtho[1,2-b]bipyrido[2,3-h;3,2-f]quinoxaline and bis(2-(diphenylphosphanyl)phenyl) ether, respectively] is synthesized with acenaphtho[1′,2′:5,6]pyrazino[2,3-f][1,10]phenanthroline in the presence of [Cu(CH₃CN)₄]BF₄ and DPEphos in CH₂Cl₂ at room temperature for 2 h (Scheme 152) [148].

Scheme 152

Synthesis of diimine Cu(I) complex [Cu(ABPQ)(DPEphos)]BF₄

68 Synthesis of Spiro-quinazoline/Pyrimidine Derivatives

Synthesis of novel the biologically important spiro[quinazoline/pyrimidine]ones 364, 365 was described using HCl (10 mol%) in a one-pot, three-component condensation of barbituric acid 68a, acenaphthoquinone 1, and urea or thiourea 363 in refluxing EtOH (Scheme 153) [149].

Scheme 153

Synthesis of spiro[quinazoline/pyrimidine]ones

69 Synthesis of 9-(Alkyl or aryl)acenaphtho[1,2-b]furan-8-(alky or aryl)amine Compounds

In 2012, Sandaroos and coworkers described the synthesis of 9-(alkyl or aryl)acenaphtho[1,2-b]furan-8-(alky or aryl)amine compounds 368 by one-pot reaction of (acenaphthylen-1-yloxy)trimethylsilane 367, alkyl and aryl aldehydes 81, and aryl and alky isocyanides 366 in refluxing DMF (Scheme 154) [150].

Scheme 154

Synthesis of 9-(alkyl or aryl)acenaphtho[1,2-b]furan-8-(alky or aryl)amine compounds

70 Conclusions

This review has summarized the use of acenaphthoquinone in the synthesis of heterocyclic compounds with respect to the number of atoms in heterocyclic rings, taking into consideration the heteroatom. We have shown that acenaphthoquinone is a very versatile substrate, as it can be used for the synthesis of a large variety of heterocyclic compounds. Acenaphthoquinone has been developed in the synthesis of spiro[4H-pyran] derivatives, spiro acenaphthylenes, dispiro oxindolopyrrolidines/pyrrolizidines, spiro[indoline-3,2′-quinazoline, dispirodihydrofuranyl oxindoles, spiro1H-pyrrolo[2,3-b]pyridines, spiro dihydropyridines, spiro[isoindoline-1,2′-quinazoline and etc. Many synthetic compounds also exhibit potential antimicrobial activities. There is a wide range of multicomponent reactions that include acenaphthoquinone in the synthesis of various organic compounds. This review purpose to show deputation examples of these multicomponent reactions in recent years. We can still expect many further developments of this compound in synthetic chemistry.