Sulfonic acids derived from hydroxylamine

Reaction of 3-formyM/7-pyrido[ 1,2- ]pyrimidin-l-ones with hydroxylamine O-sulfonic acid at 5 °C, then 50 °C yielded 3-nitriles <2003T4113>. Treatment of 2-hydroxy-3-(dimethylamono)methyF4//-pyrido[l,2- ]pyrimidin-4-one with Mel, then with KCN gave the 3-cyanomethyl derivative <2004MI215>. A condensation product was obtained from 5-amino-l-ethyl-6-hydroxy-l,3-dihydrobenzimidazol-2-one and 3-lbrmyl-2-hydroxyA//-pyndo[ 1,2- ]pynmidin-l-one <2002W002/38549>. l-(2-Aminopyrimidin-4-yl)-8-phenyl-l,2,3,4-tetrahydro-6//-pyrido[l,2- ]pyrimidin-6-ones were prepared from l-(2-methylthiopyrimidin l-yl)-8-phenyl-l,2,3,4-tetrahydro-6//-pyrido[l,2- ]pyrimidin-6-one by treatment with MCPBA, and then with aralkylamines <2005W005/070932>. 

Direct amination of benzo[l,2-aqueous base with hydroxylamine-0-sulfonic acid gives a mixture of three diamino derivatives and two monoamino derivatives (Equation (15)). The combined yields of diamino and monoamino products are 45% and 48%, respectively. The three diamino derivatives can be separated by fractional crystallization from ethanol <86JOC979>. A-Amination of triazoles can also be achieved by treatment with NaH in DMF followed by O-amino-2,4-dinitrophenol <85TL335> or 0-(mesitylsulfonyl)hydroxyamine (9lJCS(Pl)2045>. 

It is interesting to contrast this substitution reaction with a complementary method for achieving the hydroxyalkylation of pyridines and quinolines developed by Minisci et al. <85T617>. They found that addition of hydroxylamine-(9-sulfonic acid to an acidic solution of 4-cyanopyridine in methanol containing catalytic iron(Il) sulfate, gave 2-(hydroxymethyl)-4-cyanopyridine 70 on work-up (Scheme 25). No products derived from ipso-substitution of the cyano-fiinction were observed. 

When it is desired to make 1,2-diaminobenzimidazoles, the compounds can be prepared directly from acetyl 2-aminophenylhydrazines (12) and cyanogen bromide [173, 174] with subsequent hydrolysis of the 1-amido derivative (Scheme 3.1.15). It may, however, be more convenient to Al-aminate a 2-aminobenzimidazole directly using -(2,4-dinitrophenyl)hydroxylamine or hydroxylaminc -sulfonic acid [174, 175], which gives yields in the range 40-76%. 

Electrophilic N-aminations have been performed with hydroxylamine-O-sulfonic acid (HOSA)," O-(2,4-dinitrophenyl)hydroxylamine and C>-mesitylenesulfonylhydroxylamine. The use of HOSA is mainly restricted to aqueous reaction media. Imide sodium salts of some heterocycles such as theobromine (88) can be converted to hydrazine derivatives by treatment with 0-(diphenylphosphinyl)hydroxylamine (equation 35)." This reaction has been extended to synthesis of N-arylhyd ines, where R and R are hydrogen, alkyl or aryl (equation 36)." Similarly, trisubstituted hydrazines can be prepared by the use of N-aryl-O-acetylhy oxylamines and secondary amines." A recent publication" concerning the synthesis of l-acyl-2-dkylhydrazines from hydroxamic acids and amines in the presence of activating agents has been found to be erroneous no N—N bond formation occurs under these conditions." ... 

SAR studies were performed on compoimds containing the 9H-isothia-zolo[5,4-fc]quinoline-3,4-dione (ITQ) nucleus and it was found that some of them are potent antibacterial agents (see Scheme 101) [114,115]. They were prepared from compound 353, which was treated with cyclopropyl isothiocyanate in DMF and then with Mel. Compound 354 (94%) was obtained and treated with in NaH in DMF to give the isothiazolo[ 5,4-fo] quinoline compound 355 (93%). Its treatment with anhydrous NaSH gave the corresponding mercaptan (84%), which was directly cychsed without purification to 356 (85%) in the presence of hydroxylamine-O-sulfonic acid. Microwave-assisted Suzuki-Miyaura cross-coupling of the ITQ nucleus 356 with the desired aryl-boronic esters or acids afforded derivatives 357, typically, in 30-50% yield after HPLC purification (Scheme 87). 

Isoquinoline V-imines also have been made only by deprotonation of V-aminoisoquinolinium salts. Just as for the corresponding pyridinium derivatives (see Section II,A,1), the salts 43 can be produced by amination of isoquinoline with hydroxylamine-O-sulfonic acid75 or from V-(2,4-di-nitrophenyl) isoquinolinium chloride (44), 30 31 76 Substituted quaternary amino salts (46) are obtained by cyclization of 2-(2,4-dinitroanilino)-o-styrylaldehyde hydrazones (45) with ethanolic hydrochloric acid, and deprotonation to V-imines is easily effected by alkali. On liberation from the salts by alkali, unsubstituted isoquinoline V-imines dimerize to give... 

Two syntheses of benzocinnoline Ar-imines have been described recently.78 They can be prepared from benzocinnoline and hydroxy lamine-O-sulfonic acid or by diazotization of 2,2 -diaminobiphenyl with pentyl nitrite or JV-nitrosodiphenylamine. Diazotization of the diamine presumably proceeds via the triazepine 48, which is isomeric with unsubstituted benzocinnoline iV-imine. Benzocinnoline iV-imine itself, the only unsubstituted iV-imine so far isolated, was prepared from benzocinnoline and hydroxylamine-O-sulfonic acid. Under similar conditions, quaternary IV-amino salts were isolated from the other iV-heterocycles. The unsubstituted Ar-imine can be converted easily into the acyl, sulfonyl, and 2,4-dinitrophenyl derivatives (Scheme 3). 

An aq. soln. of NaHCOg added to a stirred soln. of / -ionone oxime (prepared from / -ionone, hydroxylamine hydrodiloride, and K-carbonate in water-ethanol) in tetrahydrofuran, protected from light, KI and iodine in water added, and refluxed 4 hrs. -> isoxazole deriv. (Y 91%) mixed with liq. NHg, tetrahydrofuran, and rerf-butanol, treated with Na until the soln. remains dark blue, stirred 15 min., and the crude / -aminoketone refluxed 24 hrs. with a trace of p-toluene-sulfonic acid in toluene / -damascone (Y 84%). F. e. s. G. Budii and J. C. Vederas, Am. Soc. 94, 9128 (1972) s. a. K. H. Sdiulte-Elte, B. L. Muller, and G. Ohloff, Helv. 56, 310 (1973). 

A sulfonamide derived from a primary amine, treated with hydroxylamine-O-sulfonic acid or chloramine in alkaline solution... 

Amines can be obtained under mild conditions from amides by reduction with borane and also from ethylene derivatives with borane and hydroxylamine-O-sulfonic acid or chloramine A modified Schmidt reaction gives good yields of N-subst. trifluoro-acetamides... 

Organoboranes derived from terminal olefins or relatively unhindered olefins are readily converted to the corresponding amine by treatment with chloroamine or hydroxylamine-O-sulfonic acid [16]. 

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