59743-84-9

Basic information

• Product Name: Benzo[b]thiophen-10-methoxycycloheptanone
• Synonyms: BENZOTHIOPHEN-10-METHOXY-CYCLOHEPTANONE;10-Methoxy-4-Benzo[4,5]Cyclohepta[1,2-B]Thiophene-4-One;Benzo[b]thiophen-10-methoxycycloheptanone;10-Methoxy-4h-Benzo(4,5)Cyolohepta(1,2-B)Thiophen-4-One;Benzothiophene-10-methoxycycloheptanone;10-METHYOXY-4H-BENZO(4,5)CYOLOHEPTA(1,2-B)THIOPHEN-4-ONE;10-methoxy-4H-benzo[4,5]-cycloheta[1,2-b]thiophen-4-one(for Ketotifen);10-METHOXY-4H-BENZO(4,5)CYCLOHEPTA(1,2-BETA)THIOPHENE-4-ONE
• CAS NO: 59743-84-9
• Molecular Formula: C₁₄H₁₀O₂S
• Molecular Weight: 242.297
• Mol File: 59743-84-9.mol
• Article Data: 4

Chemical Properties

• Melting Point: 164-166 °C(Solv: methanol (67-56-1))
• Boiling Point: 436.4 °C at 760 mmHg
• Flash Point: 217.7 °C
• Appearance: light yellow crystal powder
• Density: 1.32 g/cm³
• Vapor Pressure: 8.11E-08mmHg at 25°C
• Refractive Index: 1.661
• Storage Temp.: 2-8°C
• CAS DataBase Reference: Benzo[b]thiophen-10-methoxycycloheptanone(CAS DataBase Reference)
• NIST Chemistry Reference: Benzo[b]thiophen-10-methoxycycloheptanone(59743-84-9)
• EPA Substance Registry System: Benzo[b]thiophen-10-methoxycycloheptanone(59743-84-9)

Safety Data

• Hazardous Substances Data: 59743-84-9(Hazardous Substances Data)

Usage

General Description

Benzo[b]thiophen-10-methoxycycloheptanone is a chemical compound with a molecular formula C13H16OS. It belongs to the class of organic compounds known as thiochromanones, which are compounds containing a thiochroman-4-one skeleton. This chemical is characterized by its cyclic structure containing a benzo[b]thiophen ring and a cycloheptanone ring with a methoxy group attached to it. It is used in pharmaceutical and chemical research as a building block in the synthesis of various compounds and materials. Its specific properties and potential applications depend on its structural properties and chemical reactivity.

InChI:InChI=1/C14H10O2S/c1-16-12-8-9-4-2-3-5-10(9)13(15)11-6-7-17-14(11)12/h2-8H,1H3

Synthetic route

methanol (67-56-1) + 9,10-dibromo-9,10-dihydro-4H-benzo<4,5>cyclohepta<1,2-b>thiophene-4-one (34580-10-4) → 10-methoxy-4H-benzo<4,5>cyclohepta<1,2-b>thiophen-4-one (59743-84-9)

Conditions	Yield
Stage #1: methanol; 9,10-dibromo-9,10-dihydro-4H-benzo<4,5>cyclohepta<1,2-b>thiophene-4-one In water for 4h; Reflux; Stage #2: With K2O/MgO In water for 4h; Reagent/catalyst; Reflux;	59.59%

9,10-dibromo-9,10-dihydro-4H-benzo<4,5>cyclohepta<1,2-b>thiophene-4-one (34580-10-4) → 10-methoxy-4H-benzo<4,5>cyclohepta<1,2-b>thiophen-4-one (59743-84-9) + 9-methoxy-4H-benzo<4,5>cyclohepta<1,2-b>thiophene4-one (126939-24-0)

Conditions	Yield
mother liquors after XXIV diluted warwe and extracted with dichlormethane; Yield given. Multistep reaction. Yields of byproduct given. Title compound not separated from byproducts;

9,10-dihydro-4H-4-oxobenzo<4,5>cyclohepta<1,2-b>thiophene (1622-55-5) → 10-methoxy-4H-benzo<4,5>cyclohepta<1,2-b>thiophen-4-one (59743-84-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: N-bromosuccinimide, dibenzyl peroxide / CCl4 / 3 h / Heating; alkaline mother methanolic liquor after XXII was diluted with water and extracted dichlormethane 2: mother liquors after XXIV diluted warwe and extracted with dichlormethane View Scheme

methanol (67-56-1) + C13H6Br2OS → 10-methoxy-4H-benzo<4,5>cyclohepta<1,2-b>thiophen-4-one (59743-84-9)

Conditions	Yield
Stage #1: methanol; C13H6Br2OS for 7h; Reflux; Stage #2: With potassium hydroxide for 3h; Reflux;	25.8 g

10-methoxy-4H-benzo<4,5>cyclohepta<1,2-b>thiophen-4-one (59743-84-9) → 10-methoxy-4H-benzo<4,5>cyclohepta<1,2-b>thiophene (60587-37-3)

Conditions	Yield
With lithium aluminium tetrahydride; aluminium trichloride In tetrahydrofuran; diethyl ether for 0.5h; Heating; reagents was added at 5 deg C;	85%
aluminium chloride

10-methoxy-4H-benzo<4,5>cyclohepta<1,2-b>thiophen-4-one (59743-84-9) + (1-methyl-4-piperidyl)magnesium chloride (63463-36-5) → 10-methoxy-4-(1-methyl-4-piperidyl)-4H-benzo<4,5>cyclohepta<1,2-b>thiopene-4-ol (59743-88-3, 116655-77-7, 116667-71-1)

Conditions	Yield
With tetrahydrofuran

4-chloro-1-methylpiperidine (5570-77-4) + 10-methoxy-4H-benzo<4,5>cyclohepta<1,2-b>thiophen-4-one (59743-84-9) → 10-methoxy-4-(1-methyl-4-piperidyl)-4H-benzo<4,5>cyclohepta<1,2-b>thiopene-4-ol (59743-88-3, 116655-77-7, 116667-71-1)

Conditions	Yield
With magnesium 1)Grignard reagent in THF 2)15 deg C, 50min, educt XXIV 3)1.5h room temp.; Yield given. Multistep reaction;

10-methoxy-4H-benzo<4,5>cyclohepta<1,2-b>thiophen-4-one (59743-84-9) + 4-Bromotetrahydrothiopyran (32358-88-6) → 10-methoxy-4H-benzo<4,5>cyclohepta<1,2-b>thiophene-4-ol + 4-(4-tetrahydrothiopyranyl)-10-methoxy-4H-benzo<4,5>cyclohepta<1,2-b>thiophene-4-ol (124939-82-8) + 4,4'-bis(tetrahydrothiopyranyl) (116196-83-9)

Conditions	Yield
With magnesium 1)preparation of Grignard reagent in ether, THF 2)5 deg C 3)1h, 5 deg C, 3h room temp.; Yield given. Multistep reaction. Yields of byproduct given;
With magnesium 1)ether, THF, 5 deg C 2)1h, 5 deg C, 3h room temp.; Yield given. Multistep reaction. Yields of byproduct given;

10-methoxy-4H-benzo<4,5>cyclohepta<1,2-b>thiophen-4-one (59743-84-9) + trimethyl phosphonoacetate (5927-18-4) → [10-Methoxy-4H-benzo[4,5]cyclohepta[1,2-b]thiophen-4-ylidene]-acetic acid methyl ester (98320-26-4) + methyl (10-methoxy-4H-benzo<4,5>cyclohepta<1,2-b>thiophen-4-ylidene)acetate (98320-27-5)

Conditions	Yield
With sodium hydride 1) paraffin oil, DMSO, 30 min. r.t., 2) DMF, 90 deg C, 15 h; Yield given. Multistep reaction. Yields of byproduct given;

10-methoxy-4H-benzo<4,5>cyclohepta<1,2-b>thiophen-4-one (59743-84-9) → ketotifen (34580-13-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: Mg / 1)Grignard reagent in THF 2)15 deg C, 50min, educt XXIV 3)1.5h room temp. 2: 97 percent / HCl / H2O / 1 h / Heating View Scheme
Multi-step reaction with 2 steps 1: THF 2: aq. HCl / 1 h / 100 °C View Scheme

10-methoxy-4H-benzo<4,5>cyclohepta<1,2-b>thiophen-4-one (59743-84-9) → 2-(1-methyl-4-hydroxy-4-piperidyl)-4H-benzo<4,5>cyclohepta<1,2-b>thiophen-10-one (103825-68-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 85 percent / lithium aluminium hydride, aluminium chloride / tetrahydrofuran; diethyl ether / 0.5 h / Heating; reagents was added at 5 deg C 2: butyllithium, hydrochloric acid / 1) -10 deg C, 1 h 2) -50 deg C, 1 h, at room temp. overnight, then hydrochloric acid View Scheme

10-methoxy-4H-benzo<4,5>cyclohepta<1,2-b>thiophen-4-one (59743-84-9) → 10-methoxy-2-(1-methyl-4-hydroxy-4-piperidyl)-4H-benzo<4,5>cyclohepta<1,2-b>thiophene (103825-67-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: 85 percent / lithium aluminium hydride, aluminium chloride / tetrahydrofuran; diethyl ether / 0.5 h / Heating; reagents was added at 5 deg C 2: butyllithium or lithium diisopropylamide, ammonium chloride / 1) -10 deg C, 1 h 2) -50 deg C, 1 h, at room temp. overnight, then aq. ammonium chloride View Scheme

10-methoxy-4H-benzo<4,5>cyclohepta<1,2-b>thiophen-4-one (59743-84-9) → 9-bromo-10-methoxy-4-(1-methyl-4-piperidyl)-4H-benzo<4,5>cyclohepta<1,2-b>thiophene-4-ol (126939-28-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: Mg / 1)Grignard reagent in THF 2)15 deg C, 50min, educt XXIV 3)1.5h room temp. 2: 49 percent / pyridine, Br2 / pyridine-d5; CHCl3 / 1)CHCl3, 1.5h 20 deg C 2)reflux View Scheme

10-methoxy-4H-benzo<4,5>cyclohepta<1,2-b>thiophen-4-one (59743-84-9) → 2-(1-methyl-4-piperylid-3-ene)-9,10-dihydro-4H-benzo<4,5>cyclohepta<1,2-b>thiophen-10-one hydrochloride (103825-69-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: 85 percent / lithium aluminium hydride, aluminium chloride / tetrahydrofuran; diethyl ether / 0.5 h / Heating; reagents was added at 5 deg C 2: butyllithium, hydrochloric acid / 1) -10 deg C, 1 h 2) -50 deg C, 1 h, at room temp. overnight, then hydrochloric acid 3: 32 percent / 3N-hydrochloric acid / 1 h / Heating View Scheme
Multi-step reaction with 3 steps 1: 85 percent / lithium aluminium hydride, aluminium chloride / tetrahydrofuran; diethyl ether / 0.5 h / Heating; reagents was added at 5 deg C 2: butyllithium or lithium diisopropylamide, ammonium chloride / 1) -10 deg C, 1 h 2) -50 deg C, 1 h, at room temp. overnight, then aq. ammonium chloride 3: 90 percent / 3N-hydrochloric acid / 1.5 h / Heating View Scheme

10-methoxy-4H-benzo<4,5>cyclohepta<1,2-b>thiophen-4-one (59743-84-9) → 2-(1-methyl-4-piperylid-3-ene)-9,10-dihydro-4H-benzo<4,5>cyclohepta<1,2-b>thiophen-10-one (103825-70-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: 85 percent / lithium aluminium hydride, aluminium chloride / tetrahydrofuran; diethyl ether / 0.5 h / Heating; reagents was added at 5 deg C 2: butyllithium, hydrochloric acid / 1) -10 deg C, 1 h 2) -50 deg C, 1 h, at room temp. overnight, then hydrochloric acid 3: 32 percent / 3N-hydrochloric acid / 1 h / Heating 4: 56 percent / sodium hydroxyde / methanol View Scheme
Multi-step reaction with 4 steps 1: 85 percent / lithium aluminium hydride, aluminium chloride / tetrahydrofuran; diethyl ether / 0.5 h / Heating; reagents was added at 5 deg C 2: butyllithium or lithium diisopropylamide, ammonium chloride / 1) -10 deg C, 1 h 2) -50 deg C, 1 h, at room temp. overnight, then aq. ammonium chloride 3: 90 percent / 3N-hydrochloric acid / 1.5 h / Heating 4: 56 percent / sodium hydroxyde / methanol View Scheme

10-methoxy-4H-benzo<4,5>cyclohepta<1,2-b>thiophen-4-one (59743-84-9) → (+)-(R)-4-(1-methyl-4-piperidylidene)-9,10-dihydro-4H-benzo<4,5>cyclohepta<1,2-b>thiopene-10-one (34580-13-7, 116655-74-4, 116655-75-5, 116655-76-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: Mg / 1)Grignard reagent in THF 2)15 deg C, 50min, educt XXIV 3)1.5h room temp. 2: 97 percent / HCl / H2O / 1 h / Heating View Scheme

10-methoxy-4H-benzo<4,5>cyclohepta<1,2-b>thiophen-4-one (59743-84-9) → Ketotifen (34580-13-7, 116655-74-4, 116655-75-5, 116655-76-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: Mg / 1)Grignard reagent in THF 2)15 deg C, 50min, educt XXIV 3)1.5h room temp. 2: 97 percent / HCl / H2O / 1 h / Heating View Scheme

10-methoxy-4H-benzo<4,5>cyclohepta<1,2-b>thiophen-4-one (59743-84-9) → 4-(1-methyl-4-piperidyl)-9,10-dihydro-4H-benzo<4,5>cyclohepta<1,2-b>thiophene (7427-74-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: Mg / 1)Grignard reagent in THF 2)15 deg C, 50min, educt XXIV 3)1.5h room temp. 2: triethylsilane, BF3(g), K2CO3, HCl / 1)CH2Cl2,-35 deg C, 15min 2)3,5 h at 0 deg C 3)H2O, K2CO3 4)reflux, 1h, HCl View Scheme

10-methoxy-4H-benzo<4,5>cyclohepta<1,2-b>thiophen-4-one (59743-84-9) → (Z)-<10-methoxy-4H-benzo<4,5>cyclohepta<1,2-b>thiophen-4-yliden>essigsaeure (98320-24-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1) NaH / 1) paraffin oil, DMSO, 30 min. r.t., 2) DMF, 90 deg C, 15 h 2: 71 percent / 2N NaOH / ethanol / 4 h / Heating View Scheme

10-methoxy-4H-benzo<4,5>cyclohepta<1,2-b>thiophen-4-one (59743-84-9) → (E)-(10-methoxy-4H-benzo[4,5]cyclohepta[1,2-b]thiophen-4-ylidene)acetic acid (98320-25-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1) NaH / 1) paraffin oil, DMSO, 30 min. r.t., 2) DMF, 90 deg C, 15 h 2: 76 percent / 2N NaOH / ethanol / Heating View Scheme

10-methoxy-4H-benzo<4,5>cyclohepta<1,2-b>thiophen-4-one (59743-84-9) → 4-(1-methyl-piperidin-4-ylidene)-4H-benzo[4,5]cyclohepta[1,2-b]thiophene-9,10-dione (43076-16-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: THF 2: aq. HCl / 1 h / 100 °C 3: SeO2 / acetic acid / 0.5 h / Heating View Scheme

10-methoxy-4H-benzo<4,5>cyclohepta<1,2-b>thiophen-4-one (59743-84-9) → 4-hydroxy-4-(1-methyl-4-piperidyl)-9,10-dihydro-4H-benzo<4,5>cyclohepta<1,2-b>thiopene-10-one (126939-27-3, 137731-93-2, 137731-94-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: THF 2: tartaric acid / H2O / 1 h / 90 °C View Scheme

10-methoxy-4H-benzo<4,5>cyclohepta<1,2-b>thiophen-4-one (59743-84-9) → 4-(1-benzyl-piperidin-4-ylidene)-4,9-dihydro-benzo[4,5]cyclohepta[1,2-b]thiophen-10-one (43076-17-1)

Conditions	Yield
Multi-step reaction with 5 steps 1: THF 2: aq. HCl / 1 h / 100 °C 3: toluene 4: aq. H2SO4 / butan-1-ol / 16 h / Heating 5: Na2CO3 / hexamethylphosphoric acid triamide / 18 h / Ambient temperature View Scheme

10-methoxy-4H-benzo<4,5>cyclohepta<1,2-b>thiophen-4-one (59743-84-9) → 4-(1-methyl-piperidin-4-ylidene)-9,10-dihydro-4H-benzo[4,5]cyclohepta[1,2-b]thiophen-10-ol (43076-12-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: THF 2: aq. HCl / 1 h / 100 °C 3: NaBH4 / aq. ethanol / 42 h / Heating View Scheme

10-methoxy-4H-benzo<4,5>cyclohepta<1,2-b>thiophen-4-one (59743-84-9) → 4-(10-oxo-9,10-dihydro-4H-benzo[4,5]cyclohepta[1,2-b]thiophen-4-ylidene)piperidine (34580-20-6)

Conditions	Yield
Multi-step reaction with 4 steps 1: THF 2: aq. HCl / 1 h / 100 °C 3: toluene 4: aq. H2SO4 / butan-1-ol / 16 h / Heating View Scheme

10-methoxy-4H-benzo<4,5>cyclohepta<1,2-b>thiophen-4-one (59743-84-9) → 4-(1-methyl-piperidin-4-ylidene)-4,9-dihydro-benzo[4,5]cyclohepta[1,2-b]thiophen-10-one (Z)-oxime (59743-93-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: THF 2: aq. HCl / 1 h / 100 °C 3: NH2OH*HCl, Py / 10 h / Heating View Scheme

10-methoxy-4H-benzo<4,5>cyclohepta<1,2-b>thiophen-4-one (59743-84-9) → 4-(1-methyl-piperidin-4-ylidene)-4,9-dihydro-benzo[4,5]cyclohepta[1,2-b]thiophen-10-one (E)-oxime (59743-92-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: THF 2: aq. HCl / 1 h / 100 °C 3: NH2OH*HCl / H2O / 1 h / 90 °C View Scheme

10-methoxy-4H-benzo<4,5>cyclohepta<1,2-b>thiophen-4-one (59743-84-9) → N-ethoxyformylnorketotifen (34580-19-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: THF 2: aq. HCl / 1 h / 100 °C 3: toluene View Scheme

10-methoxy-4H-benzo<4,5>cyclohepta<1,2-b>thiophen-4-one (59743-84-9) → 4-(1-methyl-1-oxy-piperidin-4-ylidene)-4,9-dihydro-benzo[4,5]cyclohepta[1,2-b]thiophen-10-one (88456-70-6, 137731-91-0, 137731-92-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: THF 2: aq. HCl / 1 h / 100 °C 3: aq. H2O2 / ethanol / 48 h / Heating View Scheme

10-methoxy-4H-benzo<4,5>cyclohepta<1,2-b>thiophen-4-one (59743-84-9) + ethoxycarbonylmethylen-diethylphosphonate [(C2 H5 O)2 POCH2 COOC2 H5 ] + water (7732-18-5) → [10-Methoxy-4H-benzo[4,5]cyclohepta[1,2-b]thiophen-4-ylidene]-acetic acid ethyl ester

Conditions	Yield
With hydrogenchloride; NaH In N-methyl-acetamide; dimethyl sulfoxide; ethyl acetate

Upstream product

• 67-56-1 methanol 
• 1622-55-5 9,10-dihydro-4H-benzo<4,5>cyclohepta<1,2-b>thiophen-4-one 
• 34580-10-4 9,10-dibromo-9,10-dihydro-4H-benzo<4,5>cyclohepta<1,2-b>thiophene-4-one 

Downstream Products

• 59743-88-3 10-methoxy-4-(1-methyl-4-piperidyl)-4H-benzo<4,5>cyclohepta<1,2-b>thiopene-4-ol 
• 43076-16-0 4-(1-Methyl-4-piperidyliden)-4H-benzo<4,5>cyclohepta<1,2-b>thiophen-9,10-dion 
• 126939-27-3 4-hydroxy-4-(1-methyl-4-piperidyl)-9,10-dihydro-4H-benzo<4,5>cyclohepta<1,2-b>thiopene-10-one 
• 43076-17-1 4-(1-benzyl-piperidin-4-ylidene)-4,9-dihydro-benzo[4,5]cyclohepta[1,2-b]thiophen-10-one 
• 43076-12-6 9,10-Dihydro-4-(1-methyl-4-piperidyliden)-4H-benzo<4,5>cyclohepta<1,2-b>thiophen-10-ol 
• 88456-70-6 4-(1-methyl-1-oxy-piperidin-4-ylidene)-4,9-dihydro-benzo[4,5]cyclohepta[1,2-b]thiophen-10-one 
• 98320-25-3 (E)-(10-methoxy-4H-benzo[4,5]cyclohepta[1,2-b]thiophen-4-ylidene)acetic acid 
• 98320-24-2 IX-207 887 
• 34580-13-7 Ketotifen 
• 34580-13-7 (+)-(R)-4-(1-methyl-4-piperidylidene)-9,10-dihydro-4H-benzo<4,5>cyclohepta<1,2-b>thiopene-10-one 
• 34580-13-7 ketotifen 

Relevant articles and documents

A ketotifen intermediate mother liquor recovery method

The present invention provides a containing 10 - methoxy - 4 H - benzo [4, 5] [...] [1, 2 - b] thiophene - 4 - one mother liquor recovery method, the method comprises containing 10 - methoxy - 4 H - benzo [4, 5] [...] [1, 2 - b] thiophene - 4 - one stock solution dissolved in an organic solvent, temperature, to the reaction solution adding reducing agent in the reaction, after the reaction heat filter, concentrated to dry adding crystalline solvent crystallization, of high purity can be obtained 10 - methoxy - 4 H - benzo [4, 5] [...] [1, 2 - b] thiophene - 4 - one. The method can realize the 10 - methoxy - 4 H - benzo [4, 5] [...] [1, 2 - b] thiophene - 4 - one mother liquor of effectively recycling, and the reaction process is easy to control, and does not need of complex special equipment; in addition in the mother liquor of each the impurity reduction reaction conversion, can be by a simple crystallization method of separation and purification.

4H-BENZOCYLOHEPTATHIOPHENES AND 9,10-DIHYDRO DERIVATIVES-SULFONIUM ANALOGUES OF PIZOTIFEN AND KETOTIFEN; CHIRALITY OF KETOTIFEN: SYNTHESIS OF THE 2-BROMO DERIVATIVE OF KETOTIFEN

Reaction of ketone IX with 4-tetrahydrothiopyranylmagnesium bromide and the following dehydration with thionyl chloride afforded the sulfide III which was transformed to the methiodide II (sulfonium analogue of pizotifen).Similar sequence starting from ketone XXIV and concluded by dehydration of the alcohol XX, cleavage of the enol ether, and by treatment with methyl iodide resulted in the formation of the sulfonium analogue of ketotifen (V).Three modified routes leading to ketotifen (IV) are being described.The chirality of ketotifen was proven by (1)H NMR spectrscopy with the help of,optically active NMR shift reagent.The resolution of racemic ketotifen (IV) was achieved by crystallization of salts with optically active O,O'-diacyltartaric acids and homogenous anantiomers were obtained.The X-ray crystallographic analysis of (+)-IV-O,O'-di(p-toluoyl)-(R)-tartrate led to the three- dimensional structure of the molecule of (+)-ketotifen which enabled to determine its absolute configuration to be (R).One of the products of bromination of the ketone IX, the following methanolysis and dehydrobromonation, identified as XXVII, was transformed by reaction with 1-methyl-4-piperidylmagnesium chloride, by the following acid-catalyzed dehydration, and cleavage of the enol ether to the 2-bromo derivative of ketotifen XXXIV. (R)(+)-Ketotifen (IV) was found to be the more active ketotifen enantiomer but the stereoselectivity of its action is only a partial one.The 2-bromo derivative of ketotifen (XXXIV) is much less active than ketotifen in the line antihistamine activity.