2-Hydroxythiophene

2-tert-Butoxytkiophene. A dry 1-1. three-necked flask is fitted with a mechanical stirrer (Note 1), a reflux condenser having a take-off attachment, and a 250-ml. dropping funnel with a pressure-equalizing side tube.2 A nitrogen-inlet tube is connected to the top of the condenser, and a T-tube branch of this is led to a mercury valve. The latter consists of a U-tube the bend of which is just filled with mercury. 

Although a mercury seal is preferable, a rubber tube lubricated with glycerol is an adequate seal. 

Common laboratory magnesium is as satisfactory as extremely pure sublimed magnesium. 

terf-Butyl perbenzoate is supplied by Lucidol Division, Wallace and Tiernan, Inc., Buffalo, New York, and Light and Co., Colnbrook, Bucks, England. 

Acidification of the basic solution gives 29-32 g. (80-88%) of benzoic acid if the reaction has proceeded properly. 

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Hydroxythiophene also exists mainly in ketonic forms. Electrophilic reagents react either at oxygen or at C-5. O-Methyl and O-acetyl derivatives are obtained in alkaline solution, probably through intermediacy of the anion. In acidic solution, coupling with benzenediazonium ion, a characteristic phenolic reaction, is found to take place (Scheme 72). 

Oxidation of thiophene with peracid under carefully controlled conditions gives a mixture of thiophene sulfoxide and 2-hydroxythiophene sulfoxide. These compounds are trapped by addition to benzoquinone to give ultimately naphthoquinone (225) and its 5-hydroxy derivative (226) (76ACS(B)353). The further oxidation of the sulfoxide yields the sulfone, which may function as a diene or dienophile in the Diels-Alder reaction (Scheme 88). An azulene synthesis involves the addition of 6-(A,A-dimethylamino)fulvene (227) to a thiophene sulfone (77TL639, 77JA4199). 

In the absence of oxygen, these thiolene-2-ones are rather stable and have been kept at 0°C for several months. 3-Hydroxythiophene, on the other hand, which has been prepared in low yield from 3-thio-phenemagnesium bromide in the same way as the 2-isomer, or through decarboxylation of 3-hydroxy-2-thiophenecarboxylic acid, "" is very unstable. Its IR spectrum indicates that it also exists as a tautomeric mixture largely in its enolic form. ... 

Dinitro-2-hydroxythiophene and 3-nitro-5-acetyl-2-hydroxythio-phene have been obtained from nitrochlorothiophenes through reaction with sodium formate in methanol. These compounds were colorless crystalline substances which decomposed with evolution of nitrogen oxides and formation of a dark resin even at —20°C. They gave, however, stable, colored, sodium salts, with ionization constants of the... 

The UV spectrum of 5-phenyl-3 hydroxythiophene is very similar to that of its methyl ether in alcoholic solution, indicating that it exists largely in the enol form in this solvent. The same coincidence of the wavelength maxima was also obtained for 5-phenyl-2-hydroxy-thiophene and its methyl ether. In chloroform solution, the maxima were shifted toward longer wavelengths, suggesting that the tautomeric equilibrium in this solvent is displaced more toward the keto form. ... 

The hydroxythiophenes which exist predominantly as the thiolen-2-ones also show reactions characteristic of the enol form. They can be methylated at the oxygen with dimethyl sulfate of diazomethane and they can also be acylated. - - They also react as thio-lene-2-ones showing a reactive methylene group which can be condensed with benzaldehyde. The danger of using chemical reactivity data for drawing conclusion as to the physical state of these tautomerizable systems has been pointed out. ... 

Compounds containing a reasonable proportion of an enolie hydroxyl group, i.e., C=C—OH, usually give a deep color with ferric chloride, and this has often been used as a qualitative test. In this way, 2-hydroxythiophene has been shown to exist, at least in part, in the hydroxy form, ... 

Hydroxythiophenes 56 have two possible keto tautomers (57 and 58) [for review see (86HC1)]. As has been pointed out earlier (76AHCS1, p. 229), the tautomerism of 5-substituted eompounds was extensively studied by Lawesson and eoworkers (63T1867) and by Hornfeldt (63MI1 68MI1). For 5-alkyl eompounds, only the keto forms were present, whereas with R = phenyl, thienyl and ethoxyearbonyl substantial amounts of the enol forms were deteeted. Computations for the parent system (R = H) showed that the 4 -thiobutenolide of type 57 is most stable (Table VII). 

DFT Results for 2-Hydroxythiophene and the Corresponding Keto Tautomers" (99UP1)... 

The infrared spectrum of 2-hydroxythiophene was originally interpreted as showing both vOH and vC=0 peaks indicating that it exists as a mixture of the hydroxy form 39 (R — H) and at least one of the 0X0 forms, 40 and/or 41. The ultraviolet spectrum of 2-hydroxythiophene is different from that of the corresponding methyl ether (39, R = Me) suggesting the presence of the chromophore contained in structure 40. The facts that this compound gives a positive... 

The infrared spectrum of 3-hydroxythiophene has been interpreted by Ford and Mackay- to show that it exists as a mixture of both the hydroxy (44) and the oxo forms (45). 5-Phenyl-3-hydroxythiophene apparently behaves similarly to the 2-hydroxy isomer, the ultraviolet... 

Snyder and his co-workers assigned structures 48 and 49 to these j6-hydroxythiophene derivatives on the basis of chemical evidence and infrared and nuclear magnetic resonance spectral data. Infrared and nuclear magnetic resonance spectra further indicate that compounds of type 49 exist as dimers, probably hydrogen bonded, when R = OC2H5 or CH3, but as monomeric enols when R = H. ... 

It has recently been shown that 2-hydroxythiophene exists mainly as 2(5H)-thiophenone at room temperature.3... 

The procedure described is essentially that of Lawesson and Frisell.4 2-Hydroxythiophene has been prepared in low yields by Hurd and Kreuz 5 from 2-thienylmagnesium bromide and oxygen in the presence of excess isopropylmagnesium bromide. 

The first step of the procedure illustrates a general way of preparing aryl iert-butyl ethers.416 The second step is the best way to prepare 2-hydroxythiophene, inasmuch as the yield is good and ter/-butyl perbenzoate is a readily available perester that is relatively stable. The same procedure has been used to convert several other haloaromatic compounds to hydroxyaromatic compounds in good yield4 and is probably quite general. 

Rotational equilibria of 2-carbonyl substituted thiophene and furan derivatives were calculated and show that the 2-substituent favors the anti-isomer in thiophene <96MI199>. NMR shifts of 35 alkyl 3-hydroxythiophene-2-carboxylates and 3-alkylamino-l-(3-thienyloxy)-2-propanols have been compiled and analyzed <96HC17>. 

Oxidation of thiophene with Fenton-like reagents produces 2-hydroxythiophene of which the 2(570 One isomer is the most stable (Eq. 1) <96JCR(S)242>. In contrast, methyltrioxorhenium (Vn) catalyzed hydrogen peroxide oxidation of thiophene and its derivatives forms first the sulfoxide and ultimately the sulfone derivatives <96107211>. Anodic oxidation of aminated dibenzothiophene produces stable radical cation salts <96BSF597>. Reduction of dihalothiophene at carbon cathodes produces the first example of an electrochemical halogen dance reaction (Eq. 2) <96JOC8074>. 

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