Benzo thiophene nitriles

C(2) as nucleophile. These include useful ring syntheses for benzo[A]-fused compounds. The sequence 78 79 80 (Scheme 51) has been extensively applied to obtain benzo[A]furans <1948JCS2254>, benzo ]thiophenes <1931LA(488)259>, and less frequently, indoles <1927JCS1937>. Corresponding nitriles (e.g., 81) afford 3-amino derivatives (Scheme 52). 

By introducing reasonable values (about 2 for nitrogen, 4 for oxygen) for the electron affinity parameter relative to carbon, 8, and for the induced electron affinity for adjacent atoms (32/8i = Vio), we have shown that the calculated permanent charge distributions for pyridine, toluene, phenyltrimethylammonium ion, nitrobenzene, benzoic acid, benzaldehyde, acetophenone, benzo-nitrile, furan, thiophene, pyrrole, aniline, and phenol can be satisfactorily correlated qualitatively with the observed positions and rates of substitution. For naphthalene and the halogen benzenes this calculation does not lead to results... 

Although thermally allowed, the [2 + 4] cycloaddition of thiophene with nitrile oxides leads to low yields of products, even when thiophene itself is used as solvent (77JCS(P2)706, 78T3545). The yield is improved if the dimerization of the nitrile oxide is retarded. Both mono- and bis-adducts have been isolated. The most important feature of the cycloaddition, however, is the regiospecificity (Scheme 77). In contrast, benzo[6]thiophene gave a mixture of both possible regioisomers, although not in equal amounts. 

Benzo[6]thiophene 1,1-dioxides undergo [2+4] cycloaddition with 1,3-dienes such as cyclopentadiene, anthracene, etc. (70AHC(11)177>. Cycloaddition with dipolar species such as diazoalkanes (74M550), nitrilimines (74M869) and nitrile oxides (79TL4845) have also been described (Scheme 192). 

The most direct synthesis of 2-acylbenzo[6]thiophenes involves reaction of the readily available 2-lithio derivative with acylating agents, such as nitriles, acid anhydrides, etc. (equation 19). Benzo[f>]thiophene-2-carboxylic acids are available by a variety of cyclization reactions (Section 3.15.9.2.4) and the acid chlorides or esters can be used to synthesize 2-acyl derivatives by conventional means. 

Synthesis of carboxylic acids, esters, amides and nitriles of thiophenes and benzo [b "[thiophenes... 

Bromo-,54,81,294,302,337,483,512,513 and less frequently, chloro-benzo[6]thiophenes81 are readily converted into the corresponding nitriles by heating them with cuprous cyanide in a suitable solvent. 2-Bromobenzo[6]thiophene may be smoothly converted into 2-methoxybenzo[6]thiophene183 or 2-piperidinobenzo[6]thiophene406 by heating it with sodium methoxide in the presence of cupric oxide... 

For instance in benzene and some of its homologs, carbazolyl-N-oxides 246 are detected, in thiophene the heteroanalog radical 247 is formed. On the other hand in furan a 1.4-addition takes place giving product radical 248. Analogously, reaction with anthracene leads to formation of 250. Furthermore reaction of 245 with benzo-nitrile oxides 6 yields benzimidazolyl-N.N -dioxides 249. 

Benzo[b]thiophene 1,1-dioxide 38 and its many derivatives undergo 1,3-dipolar cycloadditions with a variety of 1,3-dipoles such as nitrile oxides (Scheme 27) [123, 127, 128], nitrones (Scheme 28) [127], and nitrile imines (Scheme 29) [129,130]. 

The condensation of thioglycolates or a-thioketones onto nitriles, known as the Thorpe-Ziegler cyelization, can be employed to synthesize p-aminothiophenes. This basic strategy was utilized to synthesize a-(methylthio)thiophene 38 , 2,4-diaminothiophene 39 , benzo[fc]thiophene 40 , thieno[2,3-c]pyridazine 41 , thieno[3",2" 5, 6 ]pyrido[2, 3 4,5]thieno[2,3-c]pyridazine 42 , thieno[2,3-i ]pyridine 43 , and thieno[3,2-c]pyran-4-one 44 . 

Contrary to benzo[b]thiophen, benzo[b]selenophen is acylated at position 2. 2-Bromobenzo[b]selenophen, prepared from the 2-lithium derivative and bromine, is acylated at position 3, and from this derivative the 3-isomers could be synthesized. A large number of 2- and 3-aroylbenzo[b]seleno-phens were synthesized, either by Friedel-Crafts reaction of benzo-[bjselenophencarboxylic acid chlorides and benzenes or from benzol bjselenophens and benzoic acid chlorides. Also the reaction between Grignard reagents and nitriles was used for the synthesis of aroylbenzo[b]selenophens. 4,S-Diaminobenzo[b]selenophen has been synthesized via nitration of 5-aminobenzo[b]selenophen or via the reaction of the diazonium salt derived from the S-amino-derivative with p-sulphanilic acid. From the diamino-derivative, several fused benzo[b]selenophens, e.g. (525), (526), and (527), were prepared. Reaction of the phenyl-... 

---