Hydrochloric Acid → 2-(3-Bromothiophen-2-yl)-1,3-dioxolane

HRID 2352269Notes

Reaction equation

HRID 2352269 reaction equation
C(N1[CH2:8][CH2:7]CCC1)=O.Cl.[Br:10][C:11]1[CH:15]=[CH:14][S:13][C:12]=1[CH:16]=[O:17].S(C1C=CC(C)=CC=1)([O-])(=O)=[O:19].[NH+]1C=CC=CC=1>C1(C)C=CC=CC=1.C(O)CO>[Br:10][C:11]1[CH:15]=[CH:14][S:13][C:12]=1[CH:16]1[O:19][CH2:8][CH2:7][O:17]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 174291-PiperidinecarboxaldehydeHCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)HCID 27970793-Bromothiophene-2-carboxaldehyde

Product 1

HCID 122202112-(3-Bromothiophen-2-yl)-1,3-dioxolane

Reagents, catalysts & solvents 2

HCID 174Ethylene GlycolSolventHCID 1140TolueneSolvent

Procedure

2,3-Dibromothiophene (1) is converted to 3-Bromothiophene-2-carboxaldehyde (2) through a series of reactions with n-butyl lithium yielding 2-litho-3-bromothiophene, followed by N-formylpiperidine and 3N HCl. This 3-bromothiophene-2-carboxaldehyde (2) is then placed in toluene solution containing ethylene glycol to which is added pyridinium tosylate yielding 3-bromo-2-(2-dioxolanyl)thiophene (3). This 3-bromo-2-(2-dioxolanyl)thiophene (3) is then reacted with n-butyllithium followed by sulfur, then by methyl bromoacetate, to yield methyl 3-[2-(2-dioxolanyl)thiophene-3-yl]-3-thiapropionate (4). This methyl 3-[2-(2-dioxolanyl)thiophene-3-yl]-3-thiapropionate (4) is next dissolved in acetone and p-toluenesulfonic acid monohydrate is added in catalytic amount yielding methyl 3-(2-formylthiophene-3-yl)-3-thiapropionate (5). This methyl 3-(2-formylthiophene-3-yl)3-thiapropionate (5) is then treated in solution with piperidinium acetate yielding methyl thieno[3,2-b]thiophene-2-carboxylate (6). This methyl thieno[3,2-b]thiophene-2-carboxylate (6) is then placed in solution with lithium aluminum hydride yielding 2-hydroxymethylthieno[3,2-b]-thiophene (7). This 2-hydroxymethylthieno[3,2-b]-thiophene (7) is then added to a suspension of pyridinium chlorochromate in methylene chloride and yields thieno[3,2-b]thiophene-2-carboxaldehyde (8). This thieno[3,2-b]thiophene-2-carboxaldehyde (8) is then mixed with ethylene glycol, pyridinium tosylate and benzene yielding 2-(2-dioxolanyl)thieno[3,2-b]thiophene (9). This 2-(2-dioxolanyl)thieno[3,2-b]thiophene (9) is then reacted with n-butyllithium after which SO2 is bubbled onto the surface and N-chlorosuccinimide and NH4OH are added separately at the appropriate time. This series of steps yields 5-(2-dioxolanyl)thieno[3,2-b]thiophene-2-sulfonamide (10). This 5-(2-dioxolanyl)thieno[3,2-b]thiophene-2-sulfonamide (10) may then be reacted with p-toluenesulfonic acid monohydrate in acetone to yield 5-formylthieno[3,2-b]thiophene-2-sulfonamide (11). The 5-formylthieno[3,2-b]thiophene-2-sulfonamide (11) is then reacted with an appropriate amine yielding the intermediate iminium salt (12) which may then be reduced with NaBH4 or NaCNBH3 to give the desired 5-substituted thieno[3,2-b]thiophene-2-sulfonamide.

Sources & evidence

ORD record
ord-15d7722b5ba548b78b3bbbcfeda3f438
Source dataset
uspto-grants-1989_10
Patent number
US04876271

Reaction notes

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