Naphthalene sulfonamide

Suzuka, T., et al. 1986. Effects of phenothiazines and /V-(6-aminohexyl)-5-chloro-l-naphthalene-sulfonamide on rat colonic absorption of cefmetazole. J Pharmacobiodyn 9 460. 

Sahu, K.K., Ravichandran, V., Mourya, V.K. and Agrawal, R.K. (2007) QSAR analysis of caffeoyl naphthalene sulfonamide derivatives as HIV-1 integrase inhibitors. Med. Chem. Res., 15,418—430. 

Series of halo- and alkyl-substituted benzene- and naphthalene-sulfonamides have been obtained by this method. 

Dimethylamino)-zi-(2-amino ethyl)- 1-naphthalene sulfonamide, Gantrez AN resin reaction, 439... 

Naphthalene-l-sulfonyl chloride [85-46-1] M 226.7, m 64-67°, 68°, b 147.S°/0.9mm, 147.S°/13mm. If the IR indicates the presence of OH then treat with an equal weight of PCI5 and heat at ca 100° for 3h, cool and pour into ice + H2O, stir well and filter off the solid. Wash the solid with cold H2O and dry the solid in a vacuum desiccator over P2O5 + solid KOH. Extract the solid with pet ether (b 40-60°) filter off any insoluble solid and cool. Collect the crystalline sulfonyl chloride and recryst from pet ether or C6H6 pet ether. If large quantities are available then it can be distd under high vacuum. [Fierz-Davaid and Weissenbach Helv Chim Acta 3 2312 1920.] The sulfonamide has m 150° (from EtOH or H2O). 

Naphthalene-2-sulfonyl chloride [93-11-8] M 226.7, m 74-76°, 78°, 79°, b 148°/0.6mm, 201°/13mm. Crystd (twice) from benzene/pet ether (1 1 v/v). Purified as the 2-sulfonyl chloride. [Fierz-Davaid and Weissenbach Helv Chim Acta 3 2312 1920.] The sulfonamide has m 217° (from EtOH). 

The method illustrates the ability of the sodium hydride-dimethylformamide system to effect the alkylation of aromatic sulfonamides under mild conditions and in good yield. The method appears to be fairly general. The submitters have prepared N,N-diethyl- and N,N-di- -butyl- >-toluenesulfonamide as well as 2-(/ -tolyIsuIfonyl)benz[/]isoindoline from 2,3-bis-(bromomethyl)naphthalene, and 1 %-tolylsulfony])pyrrolidine from 1,4-dichIorobutane the yield of purified product exceeded 75% in each case. 

Typically in ring-opening reactions of aziridines, the amine functional group is retained in the product molecule. An example of such a reaction where the amine group has been lost has recently been reported <06TL977>. An intramolecular Friedel-Craft reaction of aziridine 91 leads to the expected product as an intermediate. Under the rather drastic reaction conditions, the sulfonamide is lost leading to formation of the naphthalene ring. 

In an Erlenmeyer flask capped with a rubber septum a mixture of naphthalene, 1,2-dimethoxy-ethane and enough sodium to yield an 0.5-1.0 m solution of anion radical is stirred with a glass-covered stirring bar for 1-1.5 hours, by which time the anion radical will have formed and scavenged the oxygen inside the flask. A solution of one-sixth to one-third of an equivalent of the sulfonamide in dimethoxyethane is injected by syringe and the mixture is stirred at room temperature for approximately 1 hour. Quenching with water produces amines in 68-94% isolated yields. 

A wide variety of differently substituted sulfonamides 89 were very easily desulfony-lated using lithium and a catalytic amount (4%) of naphthalene in THF at temperatures ranging between —78 °C to room temperature. After hydrolysis, the expected products 90 were isolated (Scheme 38) . 

The catechol ring system can be replaced by a great variety of other ring systems, varying from phenylether (oxprenolol, (4.64)) and sulfonamides (sotalol (4.65) to amides (labetalol, (4.66)), indoles (pindolol, (4.67) benzpindolol, (4.68)), and naphthalene (propranolol, (4.63)). 

Within their scaffolds, POPAM dendrimers also possess amine groups which can undergo protonation or coordination with metal ions. The spectroscopic and photochemical properties of the first to the fourth POPAM generation with peripheral fluorescing naphthylsulfonamide groups were compared with those of reference compounds A (N-methylnaphthalenesulfonamide) and B (N-(3-di-methylaminopropyl)-2-naphthalene-l-sulfonamide) [22] (Fig. 5.19). 

Naphthyl sulfones 253 are susceptible to nucleophilic attack at the 2-position of the naphthalene ring by the alkyllithium 134 secondary sulfonamides 254, on the other hand, surprisingly undergo perilithiation with alkyllithiums.133... 

---