36801-01-1

Basic information

• Product Name: 4-CYANOTHIOPHENOL
• Synonyms: 4-CYANOTHIOPHENOL;4-MERCAPTOBENZONITRILE;Benzonitrile, 4-mercapto- (9CI);4-Thiobenzonitrile;4-Mercaptobenzonitrile, 4-Sulphanylbenzonitrile, 4-Cyanothiophenol;4-Cyanobenzenethiol;p-Cyanobenzenethiol;p-Cyanothiophenol
• CAS NO: 36801-01-1
• Molecular Formula: C₇H₅NS
• Molecular Weight: 135.19
• Product Categories: THIOL;Aromatic Nitriles
• Mol File: 36801-01-1.mol
• Article Data: 23

Chemical Properties

• Melting Point: 51-52℃
• Boiling Point: 264℃
• Flash Point: 114℃
• Appearance: /
• Density: 1.18
• Storage Temp.: Inert atmosphere,Store in freezer, under -20°C
• Solubility: DMSO (Sparingly), Ethyl Acetate (Slightly)
• PKA: 5.05±0.10(Predicted)
• CAS DataBase Reference: 4-CYANOTHIOPHENOL(CAS DataBase Reference)
• NIST Chemistry Reference: 4-CYANOTHIOPHENOL(36801-01-1)
• EPA Substance Registry System: 4-CYANOTHIOPHENOL(36801-01-1)

Safety Data

• Hazardous Substances Data: 36801-01-1(Hazardous Substances Data)

Usage

Uses

4-Mercaptobenzonitrile is a building block used as a reactant in the synthesis and in vitro anti-hepatitis B virus activities of some ethyl 6-bromo-5-hydroxy-1H-indole-3-carboxylates.

Synthetic route

4-bromobenzenecarbonitrile (623-00-7) → 4-cyanobenzenethiol (36801-01-1)

Conditions	Yield
Stage #1: 4-bromobenzenecarbonitrile With caesium carbonate; copper(II) sulfate In dimethyl sulfoxide for 0.166667h; Inert atmosphere; Stage #2: With ethane-1,2-dithiol In dimethyl sulfoxide at 100℃; for 20h; Inert atmosphere;	100%
With copper(ll) sulfate pentahydrate; caesium carbonate; ethane-1,2-dithiol In dimethyl sulfoxide at 110℃; for 20h; Inert atmosphere;	87%
Multi-step reaction with 2 steps 1: 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; tris-(dibenzylideneacetone)dipalladium(0); N-ethyl-N,N-diisopropylamine / toluene / 14 h / 120 °C / Inert atmosphere 2: sodium methylate / methanol; mineral oil / 14 h / 0 - 20 °C View Scheme
Stage #1: 4-bromobenzenecarbonitrile With TurboGrignard In tetrahydrofuran at 0℃; for 2h; Inert atmosphere; Stage #2: With sulfur In tetrahydrofuran at 0℃; for 1h; Inert atmosphere;

4-iodobenzonitrile (3058-39-7) → 4-cyanobenzenethiol (36801-01-1)

Conditions	Yield
With copper(ll) sulfate pentahydrate; caesium carbonate; ethane-1,2-dithiol In dimethyl sulfoxide at 90℃; for 20h; Inert atmosphere;	93%
With copper(l) iodide; thiourea; L-proline; sodium t-butanolate In dimethyl sulfoxide at 90℃; for 24h; Inert atmosphere;	90%

4-mercaptobenzamide (59177-46-7) → 4-cyanobenzenethiol (36801-01-1)

Conditions	Yield
With trichlorophosphate In N,N-dimethyl-formamide at 0℃; for 2h;	93%

triphenylmethyl p-cyanophenylsulfide → triphenylmethane (519-73-3) + 4-cyanobenzenethiol (36801-01-1) + 4-tritylmercaptobenzamide

Conditions	Yield
With 2-methyl-N-cyclohexylpropanamide In N,N-dimethyl-formamide Mechanism; Rate constant; Thermodynamic data; electrolyse (Hg pool electrode); ΔG(excit.)0; other reagents (azobenzenes) with other electrode;	A 84% B 90% C 6%

4-cyanophenyl-S,N,N-dimethyl thiocarbamate (19290-43-8) → 4-cyanobenzenethiol (36801-01-1)

Conditions	Yield
With potassium hydroxide In tetrahydrofuran; methanol at 20℃; for 3h;	84%
With potassium hydroxide In tetrahydrofuran; methanol for 3h; Ambient temperature;	81%
With potassium hydroxide In methanol

4-(benzylsulfanyl)benzonitrile (150993-53-6) → 4-cyanobenzenethiol (36801-01-1)

Conditions	Yield
With aluminum (III) chloride In benzene at 20℃; for 144h; Inert atmosphere;	76%

4-fluorobenzonitrile (1194-02-1) → 4-cyanobenzenethiol (36801-01-1) + bis(4-cyanophenyl)disulfane (6339-51-1) + bis(4-cyanophenyl)sulfide (46836-99-1)

Conditions	Yield
With potassium sulfide In N,N-dimethyl-formamide at 50 - 55℃; for 21h;	A 5% B 73% C 9.5%
With potassium sulfide In N,N-dimethyl-formamide at 50 - 55℃; for 21h;	A 5% B 73% C 9.5%
With potassium sulfide In N,N-dimethyl-formamide at 50 - 55℃; for 21h;	A 5% B 73% C 9.5%

4-fluorobenzonitrile (1194-02-1) → 4-cyanobenzenethiol (36801-01-1)

Conditions	Yield
Stage #1: 4-fluorobenzonitrile With sodium sulfide In N,N-dimethyl-formamide at 20℃; for 36h; Inert atmosphere; Stage #2: With hydrogenchloride; zinc In water Cooling with ice; Inert atmosphere;	46%
Stage #1: 4-fluorobenzonitrile With sodium sulfide In N,N-dimethyl-formamide at 20℃; Stage #2: With hydrogenchloride; zinc In water at 0℃; for 1h;	18.2%

4-Cyanochlorobenzene (623-03-0) + thiourea (17356-08-0) → 4-cyanobenzenethiol (36801-01-1) + bis(4-cyanophenyl)disulfane (6339-51-1) + bis(4-cyanophenyl)sulfide (46836-99-1)

Conditions	Yield
With 4,4'-bipyridine; potassium tert-butylate In ammonia at -40℃; Rate constant; electrochemical reaction;	A 34% B 13% C 14%
With 4,4'-bipyridine; potassium tert-butylate In ammonia at -40℃; electrolysis;	A 34% B 13% C 14%

ethyl 4-cyanophenyl xanthate → 4-cyanobenzenethiol (36801-01-1)

Conditions	Yield
With potassium hydroxide In ethanol; water	30%

methanol (67-56-1) + 4-fluorobenzonitrile (1194-02-1) → methyl 4-mercaptobenzoate (6302-65-4) + 4-cyanobenzenethiol (36801-01-1) + bis(4-cyanophenyl)sulfide (46836-99-1)

Conditions	Yield
With potassium sulfide; sulfuric acid; zinc Yield given. Multistep reaction;	A n/a B 5% C 9.5%

C12H16N3S(1+)*I(1-) → 4-cyanobenzenethiol (36801-01-1)

Conditions	Yield
With buffer (pH=11) at 20℃;
With buffer (pH=11) at 20℃; Rate constant;

trifluoro-acetic acid 4-cyano-phenylsulfanylmethyl ester → 4-cyanobenzenethiol (36801-01-1)

Conditions	Yield
Stage #1: trifluoro-acetic acid 4-cyano-phenylsulfanylmethyl ester With ethanol; triethylamine Stage #2: With ammonium chloride

4-methanesulfinylbenzonitrile (60958-04-5, 121405-10-5, 97474-48-1) → 4-cyanobenzenethiol (36801-01-1)

Conditions	Yield
Stage #1: 4-methanesulfinylbenzonitrile With trifluoroacetic anhydride for 0.5h; Heating; Stage #2: With triethylamine In methanol	219 mg
Multi-step reaction with 2 steps 1.1: Heating 2.1: Et3N; EtOH 2.2: NH4Cl View Scheme

p-cyanophenyl methyl sulfide (21382-98-9) → 4-cyanobenzenethiol (36801-01-1)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: mCPBA / 0 °C 2.1: Heating 3.1: Et3N; EtOH 3.2: NH4Cl View Scheme
Multi-step reaction with 2 steps 1.1: meta-chloroperoxybenzoic acid / CHCl3 / 2 h / 0 °C 2.1: trifluoroacetic anhydride / 0.5 h / Heating 2.2: 219 mg / triethylamine / methanol View Scheme

5-p-(p-bromophenylsulphonyl)phenyl-3-mercapto-1,2,4-triazole (141212-58-0) → 4-((4-bromophenyl)thio)benzonitrile (79995-40-7) + 4-((4-bromophenyl)sulfonyl)benzonitrile (80988-12-1) + diphenyl sulfide (139-66-2) + 1-bromo-4-(phenylsulphonyl)benzene (23038-36-0) + 4,4'-dibromodiphenyl sulfide (3393-78-0) + 4-cyanobenzenethiol (36801-01-1) + para-bromobenzenethiol (106-53-6)

Conditions	Yield
at 475℃; under 2 Torr; Pyrolysis; Inert atmosphere;	A 3.6 %Chromat. B 50 %Chromat. C 1.3 %Chromat. D 11.3 %Chromat. E 15.6 %Chromat. F 2.2 %Chromat. G 5.9 %Chromat.

(phenylsulphonyl)phenyl-3-mercapto-1,2,4-triazole (141212-52-4) → diphenyl sulfide (139-66-2) + diphenyl sulphone (127-63-9) + 4-(phenylsulfonyl)benzonitrile (28525-13-5) + 4-benzenesulfonyl-benzoic acid amide (55204-60-9) + 4-cyanobenzenethiol (36801-01-1) + thiophenol (108-98-5)

Conditions	Yield
at 475℃; under 2 Torr; Pyrolysis; Inert atmosphere;	A 0.4 %Chromat. B 6.4 %Chromat. C 67.1 %Chromat. D 5.7 %Chromat. E 0.6 %Chromat. F 5.9 %Chromat.

4-cyanophenyl-O,N,N-dimethyl thiocarbamate (20994-09-6) → 4-cyanobenzenethiol (36801-01-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 200 °C / Inert atmosphere 2: potassium hydroxide / methanol; tetrahydrofuran / 3 h / 20 °C View Scheme

4-cyanophenol (767-00-0) → 4-cyanobenzenethiol (36801-01-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1,4-diaza-bicyclo[2.2.2]octane / N,N-dimethyl-formamide / 65 °C 2: 200 °C / Inert atmosphere 3: potassium hydroxide / methanol; tetrahydrofuran / 3 h / 20 °C View Scheme

methyl 3-((4-cyanophenyl)thio)propanoate → 4-cyanobenzenethiol (36801-01-1)

Conditions	Yield
With sodium methylate In methanol; mineral oil at 0 - 20℃; for 14h;	1.79 g

4-Cyanochlorobenzene (623-03-0) → 4-cyanobenzenethiol (36801-01-1)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sodium hydride / mineral oil; N,N-dimethyl-formamide / 0.5 h / 10 °C / Inert atmosphere 1.2: 14 h / 20 °C / Inert atmosphere 2.1: aluminum (III) chloride / benzene / 144 h / 20 °C / Inert atmosphere View Scheme

potassium ethyl xanthogenate (140-89-6) + 4-Aminobenzonitrile (873-74-5) → 4-cyanobenzenethiol (36801-01-1)

Conditions	Yield
Stage #1: 4-Aminobenzonitrile With hydrogenchloride In water at 0℃; for 0.166667h; Stage #2: With sodium nitrite In water at 0℃; for 1h; Stage #3: potassium ethyl xanthogenate Further stages;

4-cyanobenzenethiol (36801-01-1) + p-Methoxybenzyl bromide (2746-25-0) → 4-[(4-methoxybenzyl)thio]benzonitrile (1257086-86-4)

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 20 - 80℃; for 18h;	100%

4-cyanobenzenethiol (36801-01-1) → p-cyanobenzenesulfonyl chloride (49584-26-1)

Conditions	Yield
With N-chloro-succinimide; isopropyl alcohol In dichloromethane at 0 - 20℃; for 1h;	99%

4-cyanobenzenethiol (36801-01-1) + 1-O-acetyl-2,6-anhydro-4-deoxy-3-O-methyl-6-thio-D-lyxo-hexospyranose → 40cyanophenyl 3-S-(4-cyanophenyl)-2,6-thioanhydro-4-deoxy-2,3-dithio-β-D-arabino-hexopyranoside

Conditions	Yield
With trimethylsilyl trifluoromethanesulfonate In 1,2-dichloro-ethane at 0℃; for 0.5h;	97%

4-cyanobenzenethiol (36801-01-1) + 1,3-di-O-acetyl-2,5-anhydro-4-deoxy-6-thio-α-D-xylo-hexoseptanose (316376-13-3) → 4-cyanophenyl 3-O-acetyl-2,5-anhydro-4-deoxy-1,6-dithio-α-D-xylo-hexoseptanoside (316376-15-5)

Conditions	Yield
With trimethylsilyl trifluoromethanesulfonate In 1,2-dichloro-ethane at 20℃; for 1h;	97%

4-cyanobenzenethiol (36801-01-1) + isopropyl bromide (75-26-3) → 4-(isopropylsulfanyl)benzonitrile

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 60℃; for 16h;	96.85%

4-cyanobenzenethiol (36801-01-1) → bis(4-cyanophenyl)disulfane (6339-51-1)

Conditions	Yield
With TiO2/MoS2 (10:1 molar ratio of Ti to Mo) nanocomposite; air In ethanol at 20℃; Irradiation; Green chemistry;	95%
With hydrogen bromide; dimethyl sulfoxide In chloroform at 20℃; for 8h; Inert atmosphere; Schlenk technique;	91%
With dimethyl sulfoxide at 65℃;	78%
With iodine; potassium iodide
With iodine

4-cyanobenzenethiol (36801-01-1) + methyl 1,3,4,5-tetra-O-acetyl-2,6-anhydro-D-mannose hemiacetal (354150-48-4) → 3,4,5-tri-O-acetyl-2,6-anhydro-D-mannose S-4-cyanophenyl O-methyl monothiohemiacetal

Conditions	Yield
With trimethylsilyl trifluoromethanesulfonate In 1,2-dichloro-ethane at -10℃; for 0.5h;	95%

1,5-dibromo-pentane (111-24-0) + 4-cyanobenzenethiol (36801-01-1) → 1,5-bis[(4-cyanophenyl)thio]pentane

Conditions	Yield
Stage #1: 4-cyanobenzenethiol With potassium carbonate In N,N-dimethyl-formamide at 130℃; for 0.333333h; Williamson ether synthesis; Stage #2: 1,5-dibromo-pentane In N,N-dimethyl-formamide at 130 - 140℃; Williamson ether synthesis;	94%

4-cyanobenzenethiol (36801-01-1) + 4-chlorobenzonitrile (100-00-5) → 4-cyanophenyl 4′-nitrophenyl sulfide (21969-10-8)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 80℃; Inert atmosphere;	93%

4-cyanobenzenethiol (36801-01-1) + 1,5-anhydro-3,4-di-O-benzoyl-5-thio-D-threo-pent-1-enitol (189382-65-8) → 4-cyanophenyl 3,4-di-O-benzoyl-2-deoxy-1,5-dithio-D-threo-pentopyranoside (189382-68-1)

Conditions	Yield
Stage #1: 1,5-anhydro-3,4-di-O-benzoyl-5-thio-D-threo-pent-1-enitol With hydrogen bromide In toluene at 10℃; for 0.333333h; Addition; Stage #2: With silver(I) acetate In toluene; acetonitrile at 20℃; for 2h; Substitution; Stage #3: 4-cyanobenzenethiol With trimethylsilyl trifluoromethanesulfonate In dichloromethane; toluene; acetonitrile at -10 - 20℃; for 1h; Condensation;	91%

S,S-diphenylsulphoximine (22731-83-5) + 4-cyanobenzenethiol (36801-01-1) → S,S-diphenyl-N-(4-cyanphenylthio)sulfoximine

Conditions	Yield
With Cu(4-N,N-dimethylaminopyridine)4I; oxygen In dichloromethane at 20℃;	91%

4-cyanobenzenethiol (36801-01-1) + (difluoromethyl)triphenylphosphonium trifluoromethanesulfonate → 4-((difluoromethyl)thio)benzonitrile (4837-25-6)

Conditions	Yield
With N,N,N,N,-tetramethylethylenediamine; tris[2-phenylpyridinato-C2,N]iridium(III) In acetonitrile at 20℃; for 48h; Schlenk technique; Sealed tube; Inert atmosphere; Irradiation;	90%

4-cyanobenzenethiol (36801-01-1) + C15H6BBr5F2N2O → C29H14BBr3F2N4OS2

Conditions	Yield
With potassium carbonate In acetonitrile	90%

4-cyanobenzenethiol (36801-01-1) + benzyl alcohol (100-51-6) → 4-(benzylsulfanyl)benzonitrile (150993-53-6)

Conditions	Yield
With nanolayered cobalt-molybdenum sulphide with Co/(Mo+Co) mole ratio 0.83 In Hexadecane; toluene at 180℃; under 2625.26 Torr; for 18h; Inert atmosphere; Autoclave; chemoselective reaction;	90%

4-cyanobenzenethiol (36801-01-1) → 4-(aminomethyl)benzenethiol

Conditions	Yield
With lithium aluminium tetrahydride In tetrahydrofuran for 4h; Inert atmosphere; Reflux;	89%
With hydrogenchloride; oxalic acid In water at 20℃; for 0.75h; Kinetics; UV-irradiation; chemoselective reaction;	93 %Chromat.

4-cyanobenzenethiol (36801-01-1) + 1,3-chlorobromopropane (109-70-6) → 4-[(3-chloropropyl)sulfanyl]benzonitrile

Conditions	Yield
With triethylamine In tetrahydrofuran at 20℃;	89%

4-cyanobenzenethiol (36801-01-1) + 1,4-di-O-acetyl-2,5-anhydro-3-O-methyl-6-thio-α-L-guloseptanose (316376-25-7) → 4-cyanophenyl 4-O-acetyl-2,5-anhydro-3-O-methyl-1,6-dithio-α-L-guloseptanoside (316376-27-9)

Conditions	Yield
With trimethylsilyl trifluoromethanesulfonate In 1,2-dichloro-ethane at 20℃; for 1h;	88%

4-cyanobenzenethiol (36801-01-1) + 1-O-acetyl-2,5-anhydro-3,4-di-O-methanesulfonyl-6-thio-α-D-glucoseptanose (59647-83-5) → 4-cyanophenyl 2,5-anhydro-3,4-di-O-methanesulfonyl-1,6-dithio-α-D-glucoseptanoside

Conditions	Yield
With trimethylsilyl trifluoromethanesulfonate In 1,2-dichloro-ethane at 20℃; for 1h;	88%

4-cyanobenzenethiol (36801-01-1) + silver(I) acetate (563-63-3) + triphenylphosphine (603-35-0) → Ag6(SC6H4CN)6(P(C6H5)3)6

Conditions	Yield
In tetrahydrofuran AgOAc and PPh3 dissolved in THF; HSC6H4CN added; soln. stirred for 2 h; layered with hexane for 3 d; elem. anal.;	88%

S-quinolin-3-ylbenzothioate + 4-cyanobenzenethiol (36801-01-1) → 4-(quinolin-3-ylsulfanyl)benzonitrile (1299398-65-4)

Conditions	Yield
With copper(l) iodide; potassium carbonate; ethylene glycol In N,N-dimethyl acetamide at 110℃; for 48h; Inert atmosphere;	87%

1,1-Diphenylmethanol (91-01-0) + 4-cyanobenzenethiol (36801-01-1) → 4-(benzhydrylthio)benzonitrile

Conditions	Yield
With palladium diacetate; sodium 3-(diphenylphosphanyl)benzenesulfonate In water at 120℃; for 16h; Sealed tube; Green chemistry;	86%
With dichloro bis(acetonitrile) palladium(II) In water at 120℃; for 16h; Sealed tube;	69%
With sulfuric acid In acetic acid

4-cyanobenzenethiol (36801-01-1) + 5-iodo-6-(trifluoromethyl)pyrimidine-2,4-diol → 4-((2,4-dihydroxy-6-(trifluoromethyl)pyrimidin-5-yl)thio)benzonitrile

Conditions	Yield
With copper(I) thiophene-2-carboxylate; potassium carbonate In N,N-dimethyl-formamide at 130℃; for 19h; Inert atmosphere;	86%

thiophosgene (463-71-8) + 4-cyanobenzenethiol (36801-01-1) → (p-Cyanphenyl)chlordithioformiat

Conditions	Yield
With sodium hydroxide	85%

4-cyanobenzenethiol (36801-01-1) + 1,5-di-O-acetyl-2,6-anhydro-3-O-(4-nitrobenzoyl)-2-thio-α-D-altrofuranose (321157-02-2) → 4-cyanophenyl 5-O-acetyl-2,6-anhydro-3-O-(4-nitrobenzoyl)-2-thio-α-D-altrofuranoside

Conditions	Yield
With boron trifluoride diethyl etherate In 1,2-dichloro-ethane at 20℃; for 1h;	85%

4-cyanobenzenethiol (36801-01-1) + Acetic acid (2S,3R,4R,5R)-4,5-diacetoxy-2-diacetoxymethyl-tetrahydro-pyran-3-yl ester → 3,4,5-tri-O-acetyl-2,6-anhydro-D-altrose bis(4-cyanophenyl) dithioacetal

Conditions	Yield
With trimethylsilyl trifluoromethanesulfonate In 1,2-dichloro-ethane at 20℃; for 24h;	85%

Upstream product

• 140-89-6 potassium ethyl xanthogenate 
• 873-74-5 4-Aminobenzonitrile 
• 59177-46-7 4-mercaptobenzamide 
• 623-03-0 4-Cyanochlorobenzene 
• 150993-53-6 4-(benzylsulfanyl)benzonitrile 
• 623-00-7 4-bromobenzenecarbonitrile 
• 767-00-0 4-cyanophenol 
• 20994-09-6 4-cyanophenyl-O,N,N-dimethyl thiocarbamate 
• 3058-39-7 4-iodobenzonitrile 
• 141212-52-4 (phenylsulphonyl)phenyl-3-mercapto-1,2,4-triazole 
• 141212-58-0 5-p-(p-bromophenylsulphonyl)phenyl-3-mercapto-1,2,4-triazole 
• 21382-98-9 p-cyanophenyl methyl sulfide 
• 60958-04-5 4-methanesulfinylbenzonitrile 
• 17356-08-0 thiourea 

Downstream Products

• 51238-46-1 4-(phenylthio)benzonitrile 
• 560134-54-5 ethyl 4-{2-[(4-cyanophenyl)thiocarbonyl]phenyl}-2-butenoate 
• 560134-55-6 S-(4-cyano)phenyl-5-methoxy-2-(prop-2-enyl)benzenecarbothioate 
• 560134-52-3 S-(4-cyano)phenyl 2-(prop-2-enyl)benzenecarbothioate 

Relevant articles and documents

Two efficient and practical syntheses of methyl 4-mercaptobenzoate

Two efficient syntheses of methyl-4-mercaptobenzoate are described, one utilizing the dianion of 4-bromothiophenol, the other a S(N)Ar reaction starting with 4-fluorobenzonitrile.

Copper-Catalyzed Electrophilic Thiolation of Organozinc Halides by Using N-Thiophthalimides Leading to Polyfunctional Thioethers

(Hetero)aryl, benzylic, and alkyl zinc halides were thiolated with N-thiophthalimides at 25 °C within 1 h in the presence of 5–10 % Cu(OAc)2?H2O to furnish the corresponding polyfunctionalized thioethers in good yields. This electrop

Expanding the SAR of Nontoxic Antiplasmodial Indolyl-3-ethanone Ethers and Thioethers

Despite major strides in reducing Plasmodium falciparum infections, this parasite still accounts for roughly half a million annual deaths. This problem is compounded by the decreased efficacy of artemisinin combination therapies. Therefore, the development and optimisation of novel antimalarial chemotypes is critical. In this study, we describe our strategic approach to optimise a class of previously reported antimalarials, resulting in the discovery of 1-(5-chloro-1H-indol-3-yl)-2-[(4-cyanophenyl)thio]ethanone (13) and 1-(5-chloro-1H-indol-3-yl)-2-[(4-nitrophenyl)thio]ethanone (14), whose activity was equipotent to that of chloroquine against the P. falciparum 3D7 strain. Furthermore, these compounds were found to be nontoxic to HeLa cells as well as being non-haemolytic to uninfected red blood cells. Intriguingly, several of our most promising compounds were found to be less active against the isogenic NF54 strain, highlighting possible issues with long-term dependability of malarial strains. Finally compound 14 displayed similar activity against both the NF54 and K1 strains, suggesting that it inhibits a pathway that is uncompromised by K1 resistance.