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Green synthesis of biologically active heterocycles of medicinal importance: a review

Abstract

Heterocyclic moieties are basic skeletons for 80% of commercial medicines according to the US retail market in 2014–2015, yet many actual synthetic methods are not sustainable, calling for eco-friendly strategies. For instance, microwave-assisted synthesis produces molecules rapidly in excellent yields using less energy. Similarly, in nanoparticle-catalysed synthesis, the use of metal-impregnated nanoparticles provides benefits such as recyclability of catalysts, excellent yields and short reaction times. Other sustainable methods include solvent-free synthesis, ionic liquid-supported synthesis, organic synthesis in water, sonochemical synthesis and combinatorial synthesis. Here, we review the application of microwave irradiation for organic synthesis, organic synthesis in water and solvent-free synthesis in a combined manner. We present the synthesis of complex heterocyclic molecules using nanoparticles as catalysts. We emphasize green aspects of synthetic procedures.

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Abbreviations

DCC:

N,N-dicyclohexylcarbodimide

DMAP:

Dimethylaminopyridine

Na2CO3 :

Sodium carbonate

DIPEA:

N,N-diisopropylethylamine

Pd BNP:

Palladum binaphthyl

DMSO:

Dimethyl sulphoxide

LiOBu:

Lithium tert-butoxide

DABCO:

1,4-Diazabicyclooctane

CuSO4 :

Copper(II)sulphate

FeCl2 :

Iron(II) chloride

NiCl2 :

Nickel(II) chloride

AgNO3 :

Silver nitrate

DMF:

Dimethylformamide

AgI:

Silver iodide

PVP:

Polyvinylpyrrolidone

ICP-AES:

Inductively coupled plasma atomic emission spectroscopy

SDS:

Sodium lauryl sulphate

NaOH:

Sodium hydroxide

LiCl:

Lithium chloride

SiO2 :

Silicon dioxide

HClO4 :

Perchloric

TEOS:

Tetraethylorthosilicate

DDBSA:

Dodecyl benzenesulphonic acid

TEM:

Transmission electronic microscopy

PEG:

Polyethylene glycol

MeOH:

Methanol

KCN:

Potassium cyanide

DBU:

Diazabicycloundecene

CNBr:

Cyanogen bromide

NaOMe:

Sodium methoxide

Al2O3 :

Aluminium oxide

TFA:

Trifluoroacetic acid

DCM:

Dichloromethane

CuBr:

Copper(I)bromide

VEGFR:

Vascular endothelial growth factor receptor

K2CO3 :

Potassium carbonate

Cs2CO3 :

Cesium carbonate

t-BuOLi:

Lithium tertiary butoxide

CuCl:

Copper(I)chloride

NBS:

N-Bromosuccinamide

Et3N:

Triethylamine

t-BuOK:

Potassium tertiary butoxide

CuI:

Copper iodide

AgOTf:

Silver trifluoromethanesulphonate

H2O:IPA:

Water/isopropanol

Pd(OAc)2 :

Palladium(II) acetate

Fe(CO)5 :

Iron pentacarbonyl

CO:

Carbon monoxide

HCOONH4 :

Ammonium formate

EtOH:

Ethanol

TSILs:

Task-specific ionic liquids

CH3CN:

Acetonitrile

HMDS:

Hexamethyldisilazane

TMSOTf:

Trimethylsilyl trifluoromethanesulphonate

MCR:

Multicomponent reaction

Fe3O4 :

Iron oxide

ZnO:

Zinc oxide

TiO2 :

Titanium dioxide

CuO:

Copper (II) oxide

THF:

Tetrahydrofuran

DTTB:

5,7-Dichloro-4-(2,4,5-trichlorophenoxy)-2-(trifluoromethyl)-1H-benzimidazole

NH2OH·HCl:

Hydroxylamine hydrochloride

MW:

Microwave

Ar:

Aryl group

Et:

Ethyl group

CuI:

Copper Iodide

K2CO3 :

Potassium carbonate

TBAB:

Tetrabutylammonium bromide

EtOH:

Ethanol

DMTMM:

4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride

H2SO4 :

Sulphuric acid

MgSO4 :

Magnesium sulphate

Sc(OTf)3 :

Scandium(III) triflate

CH3ONa:

Sodium methoxide

NaH:

Sodium hydride

NaOtBu:

Sodium tertiary butoxide

CuSO4·5H2O:

Copper(II) sulphate pentahydrate

DMS:

Dimethylsulphate

Cu(OTf)2 :

Copper(II) trifluoromethanesulphonate

InCl3 :

Indium chloride

EDC:

1,2-Dichloroethane

Cu(OAc)2 :

Copper(II) acetate

POCl3 :

Phosphoryl chloride

NaBF4 :

Sodium tetrafluoroborate

DMF-DMA:

N,N-dimethylformamide dimethyl acetal

N2H4 :

Hydrazine

MPa:

Megapascal

Au:

Gold

Fe2O3 :

Iron(III) oxide

CuNP:

Copper nanoparticles

PS-PdONPs:

Polystyrene palladium nanoparticles

Cu2O:

Copper(I)oxide

CuFe2O4 :

Copper iron oxide

Ag:

Silver

Ru:

Ruthenium

TDSN:

Triazine dendrimer stabilized magnetic polymer

Bi:

Bismuth

Pd-BNP:

Palladium binapthyl

KI:

Potassium iodide

KF:

Potassium fluoride

CP:

Clinoptilolite

NaOAc:

Sodium acetate

Phen:

1,10-Phenanthroline

ee:

Enantiomeric excess

NMR:

Nuclear magnetic resonance

h:

Hour

min:

Minutes

COD:

1,5-Cyclooctadiene

COT:

1,3,5-Cyclooctatriene

Au/TiO2 :

Gold/Titanium dioxide

Fe(NO3)3 :

Iron(III) nitrate

Cu(NO3)2 :

Copper(II) nitrate

Pd:

Palladium

Pt:

Platium

KAuCl4 :

Potassium gold(III) chloride

NaHCO3 :

Sodium bicarbonate

PdCl2 :

Palladium(II) chloride

Pd(dba)2 :

Bis(dibenzylideneacetone)palladium(0

References

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Acknowledgements

The authors acknowledge the Chancellor and Vice Chancellor of VIT University for delivering opportunity to carry out this study. The authors thank VIT for providing “VIT SEED GRANT” for carrying out this research work. Kaushik Chanda thanks CSIR-Govt. of India for funding through Grant No. 01(2913)/17/EMR-II.

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Correspondence to Kaushik Chanda.

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Nishanth Rao, R., Jena, S., Mukherjee, M. et al. Green synthesis of biologically active heterocycles of medicinal importance: a review. Environ Chem Lett 19, 3315–3358 (2021). https://doi.org/10.1007/s10311-021-01232-9

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  • DOI: https://doi.org/10.1007/s10311-021-01232-9

Keywords

  • Heterocycles
  • Nanoparticles
  • Microwave irradiation
  • Neat
  • Water