Cyano derivatives

Electrophilic attack at oxygen is rare, alkylation normally occurring at nitrogen, but the 6-hydroxypyrido[2,3- f]pyrimidine (75) is methylated on oxygen in low yield (70CB1250), whilst the 6-cyano derivative (76) undergoes O-tosylation to (77) (75JHC311). 

Halogeno-l-methyl-l,2,3-triazoles undergo substitution reactions with amines, but the 4-halogeno analogs do not. 5-Chloro-l,4-diphenyl-l,2,3-triazole with sodium cyanide in DMSO gives the cyano derivative (63JCS2032). 1-Substituted 3-chloro- and 5-chloro-l,2,4-triazoles both react with amines. 

Anodic oxidation of 1-methylpyrazole in the presence of cyanide ions yielded 33% (344) and 6% (345) no 3-cyano derivative was formed (78RTC35). 

Methoxycarbonyl and cyano derivatives One-step process mechanism 75LA449... 

The diagrams below give STO-3G calculated charge densities for the betu l cation and its a-formyl and a-cyano derivatives. Analyze die effect of these substituents on... 

Cyano derivatives of (18) are prepared by reaction of o-phenylenediamine with o-CcH4(CO)2N(CH2) COC(CN)z=NCGH4NMe2-p. Hydrolysis of the latter compounds give intermediates of the type o-Cr,H4(CO)2N(CH2) COCOCN which on condensation with o-phenylenediamine yield 3-phthalimidoalkylquinoxalin-2-ones, ... 

Treatment of tetracyclic nitrogen bridgehead compound 433 with NaCN resulted the formation of 4-cyano derivative of 1,2,3,4,1 lu-hexahydro-6//-pyrazino[l, 2-h]isoquinoline 434 (00BMC523). 

Oxidation of C9-Amine (3) with Lead Tetraacetate. C9-Amine hydrochloride (53 mg., 0.17 mmole) was dissolved in 0.1 ml. of water and 5 ml. of acetic acid and to the solution was added lead tetraacetate (190 mg., 0.3 mmole) at 16°-18°C. in 10 minutes. Insoluble material was removed by filtration, and the filtrate was dried by lyophilization. The residue was dissolved in 5 ml. of water and the solution was placed on a column of Amberlite CG-50 (ammonium form, 1 x 10 cm.) followed by a similar treatment as described in the case of periodate oxidation. N-Cyano derivative (5.1 mg.) was obtained and proved to be identical with the N-cyano derivative obtained from the periodate oxidation. 

Aminomethyl)-4-(2-acyl-4-chlorophenyl)-l,3-thiazoles, e.g. 40a, b, prepared in situ by reduction of the 5-cyano derivative 39b, or by hydrolysis of the 5-phthalimido derivative 41a, cyclize in situ to the thiazolo[5,4-t/]-2-benzazepines, e.g. 41a, b.90... 

One member of this class, the 8-cyano derivative 2, has been described.414 X-ray crystallography shows that the scvcn-mcmbcrcd ring adopts a chair conformation with the S S bonds ranging in lengths from 205 to 206 pm. 

We include here a short discussion of diazocyclopentadiene (4.21), its 2,3,4,5-tetra-cyano derivative (4.22), and the analogous heterocyclic compound 2-diazo-4,5-di-cyanoimidazole (4.23). Their synthesis and properties are discussed in Sections 2.6 and 12.2, where it is mentioned that they show in some respects the behavior of diazonium ions, i.e., of the mesomeric structure 4.21b (also analogously for 4.22 and 4.23). 

In 2004, Alterman et al. apphed their cyanation protocol to the synthesis of N-(t-butyl)-3-(4-cyanobenzyl)-5-isobutylthiophene-2-sulfonamide [61]. Deprotection of the sulfonamide followed by carbamate formation via reaction with butyl chloroformate finally gave the target compoimd for biological evaluation as a selective angiotensin 11 AT2 receptor agonist (Scheme 65). The cyano derivative, however, showed only a low affinity for the AT2 receptor (Ki value >10 p,M). 

Tinti and coworkers compared the sweetness of the derivatives of 2-propoxy-5-nitroanilines in which the nitro group was replaced by a CN or a CO J substituent. They found that the cyano derivative is sweet (although the sweetness is only one-third that of the nitro derivative), whereas the carboxyl derivative is not this seemed to suggest that the nitro group may not be the B unit of the AH,B system, as assigned by both Shallenberger... 

In this series, too, replacement of the N-methyl by a group such as cyclopropylmethyl leads to a compound with reduced abuse potential by virtue of mixed agonist-antagonist action. To accomplish this, reduction of 24 followed by reaction with tertiary butylmagnesium chloride gives the tertiary carbinol 27. The N-methyl group is then removed by the classic von Braun procedure. Thus, reaction with cyanogen bromide leads to the N-cyano derivative (28) hydrolysis affords the secondary amine 29. (One of the more efficient demethylation procedures, such as reaction with ethyl chloroformate would presumably be used today.) Acylation with cyclopropylcarbonyl chloride then leads to the amide 30. Reduction with lithium aluminum hydride (31) followed by demethylation of the phenolic ether affords buprenorphine (32).9... 

Depending on the 7-substituent, the norcaradiene endoperoxide can be the major cycloadduct with singlet oxygen. For example, whereas the parent system (R = H) affords only about 4% of the norcaradiene endoperoxide 30a), the 7-cyano derivative... 

Twenty-two years later the isolation of the anti-pernicious anemia factor" was announced independently by Smith (5) and Riches (6). Seven years of chemical studies identified 5,6-dimethylbenzimidazole (7), D-ribose (5) and amino-propanol (9) as components of the anti-pemicious anemia factor", but the tetrapyrroline ring structure containing Co(III) awaited the X-ray crystallographic data on the cyano-derivative by Hodgkin and White (10—15). Once the structure of the antipemicious anemia factor was determined it was called Vitamin B12 (cyanocobal-amin). The recommendations of a number of commissions forms the basis of the present system of nomenclature for this molecule and these are presented in Fig. 1. 

A similar condensation of 177b with chloromethyl phosphonic dichloride gave 2-chloromethyl-l,3,2-oxazaphospholidine-2-oxide 182 which was converted into the cyano derivative 183 by reaction with potassium cyanide in anhydrous dimethyl-sulfoxide (Scheme 51) [82],... 

Scheme 51 Synthesis of 2-chloromethyl-l,3.2-oxazaphospholidine-2-oxide 182 and its conver-tion into the cyano derivative 183...

Reaction of compound 37 with bromine in chloroform results in mono-bromination a to the sulfur. Treatment of this brominated derivative with NaBH3CN in AcOH gives a mixture of products resulting from reduction of the C=N double bond and of elimination of HBr. Reaction of 44 with sodium ethoxide results in the ethoxy-substituted derivative 45, whereas reaction with pyridine gives the dehydrobrominated derivative 46. Reaction of either 44 or 46 with sodium cyanide in dimethyl sulfoxide (DMSO) gives the cyano-derivative 47 <1983HCA971> (Scheme 13). 

Internal amino64 or imino65 67 chelate functions can achieve this type of selenenyl iodide stabilisation. 2-(4,4-Dimethyl-2-oxazolinyl)benzeneselenenyl iodide66 exhibits weak iratermolecular Se- -I contacts (372.5 pm) leading to a centrosymmetric dimer with longer N -> Se bonds (213.3 pm) and shorter Se-I bonds (277.7 pm) [Figure 19(a)] compared to the strictly monomeric 4-ethyl-substituted isomer (Se-N 207.4).65 The structure is related to the dimer of the T-shaped cyano derivative [Figure 19(b)].68... 

The cyano derivative 169, through treatment with alkyllithium and reduction, afforded 3-aminoazepane 170 <00TL1179>. 

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