Formylation of selenophene

Electrophilic Substitution. The rate constants and activation parameters for the formylation of selenophen by the DMF-phosgene complex in chloroform have been determined and compared with those of the other five-membered heterocycles. Acylation of 2-benzylselenophen occurs exclusively in the a-position of the selenophen ring. Formylation and acetylation of 2-(2-thienyl)selenophen went predominantly (80 and 75%, respectively) in the a-position of the selenophen ring and 20% in the a-position of the thiophen ring. 2,5-Dimethylselenophen-3-carboxylic acid could be iodinated at position 4 with iodine-iodic acid. Bromination of 2-formylselenophen in AlCh yielded the 4-isomer. Bromination of 2-methylselenophen with N-bromosuccinimide in acetic acid gave 3,5-di-bromo-2-methylselenophen. 

Substrates 47 and 48 have also been used to study the relative reactivities of selenophene and thiophene and of selenophene and benzene.71 The higher reactivity of the selenophene ring was demonstrated by the fact that upon formylation 59% of compound 49a was formed and upon acylation 63% of derivative 49b. Acylation of 48 gave exclusively 2-acetyl-5-benzylselenophene. Structures of the products were determined by H NMR. 

V-Methyl-/V-phenylformamide has been used as an alternative amide in determination of the relative reactivities toward formylation of thiophene and selenophene (73JGU871). 

A quantitative study of acetylation, chlorination, and formylation of thieno[3,2-b]thiophene (8.185, X, Y = S), selenolo[3,2-6]thiophene (8.185, X = S, Y = Se), and selenolo[3,2-6]selenophene (8.185, X, Y = Se) gave the rates relative to thiophene given in Table 8.21 [80CS( 15)206]. Only a-substitution was observed (due to the high selectivity of the reactions), and the results clearly show that replacement of S by Se increases the reactivity (cf. the reactivity of selenophene and thiophene, Chapter 6). 

Halogenated selenophene-2-aldehydes may be obtained either from selenophene-2-aldehyde halogenated (chlorinated or brominated) by the respective V-halosuccinimide72 or by formylation of the 2-halo-selenophenes.72,73... 

The chlorine atom of chloromethyl derivatives of selenophene is very reactive and easily displaced in substitution reactions. Thus, 2-chloromethylselenophene and its homologs readily exchange the chlorine for dialkylamino, alkoxy, and acetoxy groups, and the chloromethyl can be converted into an aldehyde group, providing a synthesis for 2,5-dimethylselenophene-3-aldehyde (7) which cannot be obtained by direct formylation.102... 

FlO. 5. Plot of activation enthalpies for formylation of furan. thiophene, selenophene, and tellurophene against their resonance energies. From S. Clementi, F. Fringuelli, P. Linda, G. Marino, G. Savelli, and A. Taticchi, J. Chem. Soc.. Perkin Trans. 2, 2097 (1973). 

The dipole moments of some simple halogeno-, cyano-, and formyl-selenophens have been measured and the conformations of these compounds have been discussed. Through a study of the n.m.r. spectrum of selenophen in lyotropic mesophase, the ratios of the interproton distances were calculated from the direct couplings and found to be in good agreement with the corresponding values calculated from microwave data. ... 

Decarboxylation of the acids gave the parent compounds (541) and (542). The product of condensation between o-(methylseleno)phenylacetic acid and o-methylthio- or o-methylseleno-benzaldehydes (549) gave the tetracyclic derivatives (550). These were also obtained by Rieche formylation of (551). The pyrrole-fused selenophen (552) was prepared similarly to the... 

The effect of substituents on the reactivity of heterocyclic nuclei is broadly similar to that on benzene. Thus mem-directing groups such as methoxycarbonyl and nitro are deactivating. The effects of strongly activating groups such as amino and hydroxy are difficult to assess since simple amino compounds are unstable and hydroxy compounds exist in an alternative tautomeric form. Comparison of the rates of formylation and trifiuoroacetylation of the parent heterocycle and its 2-methyl derivative indicate the following order of sensitivity to substituent effects furan > tellurophene > selenophene = thiophene... 

A quantitative study has been made on the effect of a methyl group in the 2-position of five-membered heteroaromatic compounds on the reactivity of position 5 in the formylation and trifluoroacetylation reaction. The order of sensitivity to the activating effect of the substituent is furan > tellurophene >selenophene = thiophene (77AHC(2l)ll9). 

However, the rate of substitution of pyrrole is too high and that of benzene too low to be followed by standard techniques, and consequently a kinetic study was limited to furan, thiophene, selenophene, and tellurophene. Activation entropies are constant for all four members of the series, indicating that the arrangement of the atoms around the reaction center is similar, i.e., the transition states of all four rings occur at similar positions along the reaction coordinate. The relative rates for the formylation are thus controlled by the activation enthalpies. At 30UC relative rates are furan (107), thiophene (1), selenophene (3.64), and tellurophene (36.8).68... 

Studies of the conformations of 2-formyl and 2-acetyl derivatives of the five-membered heterocycles have attracted great interest in recent years, but some of the results have been contradictory. At low temperatures the interconversion of the two conformers, trans-SS and cis-86, is slow, and can be studied by NMR. Thus, the 1H-NMR spectra of some selenophene deriva-... 

Computer simulation of lanthanide-induced shifts in the 2-formyl and 2-acetyl derivatives of furan, thiophene, selenophene, and tellurophene108 indicate a nearly equipopulated mixture of trans and cis conformers of the furan, and a preponderance of the cis for the thiophene, selenophene, and tellurophene derivatives. This difference is due to an interaction between the ring heteroatom and the carbonyl oxygen lone pair electrons. 

Cyano-substituted selenophenes are valuable precursors of formyl derivatives.89 They are also used as starting materials for the preparation of carboxylic acids and their derivatives.128 By treating the cyano compounds with hydrogen selenide, selenoloamides (101) were obtained. As shown in... 

Substituting a formyl, carboxy, or carbalkoxy group into a thieno-thiophene or selenophenothiophene molecule has no substantial effect on Ae coupling constants but considerably affects the chemical shifts (see Litvinov and Fraenkel and Michael and Gronowitz ). The chemical shifts of the protons in the selenophene ring are characteristic of different t rpes of condensation of the thiophene and selenophene rings and increase in the order 15 > 14 > 16 irrespective of the solvent used (acetone, CCIJ. A similar sequence is observed in the carbonyl derivatives of the isomeric selenophenothiophenes. 

Substituents at C(4) do not appreciably modify the conformational equilibrium of the 2-formyl group in furan, pyrrole, thiophene, and selenophene derivatives (81RCR336). 

The reactivity of five-membered rings with one heteroatom to electrophilic reagents has been quantitatively compared. Table 1 shows that the rates of substitution for (a) formylation by phosgene and V,iV-dimethylformamide, (b) acetylation by acetic anhydride and tin(IV) chloride, and (c) trifluoroacetylation with trifluoroacetic anhydride (71AHC(13)235) are all in the sequence furan > tellurophene > selenophene > thiophene. Pyrrole is still more reactive as shown by the rate for trifluoroacetylation, by the relative rates of bromination of the 2-methoxycarbonyl derivatives (pyrrole > furan > selenophene > thiophene), and by the rate data on the reaction of the iron tricarbonyl-complexed carbocation [C6H7Fe(CO)3]+ (Scheme 5) (2-methylindole ss V-methylindole > indole > pyrrole > furan > thiophene (73CC540)). 

The trifluoroacetylation, formylation and bromination of 1-tritylpyrrole occurs regioselec-tively at the 3-position in high yield (83JCS(P1)93>. 2-Alkyl substituents orient substitution in thiophene and selenophene into the 5-position. Since the a-directing power of the ring heteroatom is more pronounced in furan than thiophene, preference for 5-substitution is still further enhanced. In pyrrole, although the ratio of a to /3 reactivity is much smaller than in the other five-membered rings, 5-substituted 2-alkylpyrroles still appear to be the major products. 

Acetylbenzo[6]tellurophene is also formed in isolable quantities. Benzo[6]selenophene is converted into 2-acyl derivatives by reaction with acid chlorides in the presence of aluminum chloride, whereas similar Friedel-Crafts acylation of benzo[6]thiophene yields 3-substituted products. When the 2-position is blocked, formylation can be directed into the 3-position. Thus treatment of 2-bromobenzo[6]selenophene with dichloromethyl butyl ether (Cl2CHOBu) and titanium tetrachloride yields the 3-formyl derivative (72BSF3955). If the 2- and 3-positions of benzo[6]selenophene are blocked with methyl groups, acylation under Friedel-Crafts conditions occurs in the 6-position (78CR(C)(287)333>. 

Amino-substituted selenophenes are in general unstable compounds, and are conveniently isolated as IV-acetyl or iV-formyl derivatives. An ortho situated electron-attracting substituent such as acetyl, formyl or nitro renders the amino compounds stable. Derivatives of this type can be diazolized and the resulting diazonium salts converted into azides (by reaction with azide ion) (75CR(C)(281)317) and selenocyanates (by reaction with selenocyanide ion) (79BSF(2)237). 3-Acetamidoselenophene can be thiocyanated or selenocyanated in the 2-position by treatment with bromine and potassium thiocyanate or potassium selenocyanate, respectively (78TL1797). 

In a similar manner, the azidoacrylates (216)-(218) obtained from the 3-formyl derivatives of furan, thiophene and selenophene were thermolyzed to yield the esters (219)-(221) of the [2,3-6] series. 

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