3-Alkyldiaziridines and 1,3-dialkyldiaziridines from aliphatic aldoxime-O-sulfonic acid salts

摘要

Mendeleev Communications Electronic Version, Issue 2. 1997 (pp. 47ndash;86) 3-Alkyldiaziridines and 1,3-dialkyldiaziridines from aliphatic aldoxime-O-sulfonic acid salts Anatolii N. Mikhailyuk, Vera Yu. Petukhova and Nina N. Makhova* N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 117913 Moscow, Russian Federation. Fax: +7 095 135 5328 It was shown for the first time that aliphatic aldoxime-O-sulfonic acids can be stabilised as ammonium or alkylammonium salts and can be used in diaziridinium synthesis with primary aliphatic amines or ammonia to give 1,3-dialkyldiaziridines and 3-alkyldiaziridines, respectively; the latter compounds have not been previously easily accessible. Among the alkyl derivatives of diaziridine, 3-alkyldiaziridines 1 are the least accessible.This is mainly due to their clear-cut tendency to undergo condensation with the starting aldehydes and with ammonia under the conditions used in their synthesis (from aliphatic aldehydes, ammonia and N-chloramine) to give 2,4,6-trialkyl-1,3,5-triazabicyclo3.1.0hexane 2.1 Mild selective acid hydrolysis of the triazolidine ring in 2 in the presence of chloral hydrate yields the chloral hydrate derivatives 3 (R = Pr, But).2andash;c Upon alkaline decomposition of 3 (R = Me, Pr, But) in the presence of benzoyl chloride, corresponding 1,2-dibenzoyl derivatives 4 were isolated.2a,c The only reported synthesis of 3- alkyldiaziridines, viz. 3-propyldiaziridine, was described in a German patent.2d This compound was prepared in 6 yield by the reaction of butyric aldehyde with ammonia and chloramine in aqueous methanol at 60 deg;C.However, the only characteristic reported for this compound was its boiling point. These literature data are presented in Scheme 1. Other known methods for the synthesis of 1,2-unsubstituted diaziridines treatment of oxime-O-sulfonic acids3 or their esters4ndash;6 with ammonia or treatment of carbonyl compounds with ammonia and hydroxylamine-O-sulfonic acid7 (HASA) are considered to be unsuitable for the preparation of 3-alkyldiaziridines, because aldoxime-O-sulfonic acids 5 and aldoxime esters decompose immediately after formation giving nitriles and the corresponding acids.The formation and decomposition of aldoxime-O-sulfonic acids 5 were also observed in the reaction described in ref. 7. In the present study, we have found conditions for the stabilisation of aldoxime-O-sulfonic acids 5. This allowed us to propose a new method for the synthesis of 3-alkyldiaziridines 1, which makes these compounds fairly accessible. Our search for the stabilisation conditions for 5 was based on the known data on the stability of HASA salts,8 which decreases in the base sequence: Et3N Py NH3 NH2NH2 KOH.We found that triethylammonium salts of aliphatic aldoxime-O-sulfonic acids 6a can be stored at 20 deg;C in a vacuum desiccator over alkali. Salts derived from primary aliphatic amines 6b are also fairly stable. However, the ammonium salts 6c proved to be stable only in a saturated aqueous solution of NH3 (40) at a reduced temperature.In 25 aqueous ammonia compounds 5 decomposed. Salts 6 were synthesised by the reaction of the corresponding amines (or NH3) with 5 in the cold. The latter, in turn, were prepared from aliphatic aldehydes and HASA in water (or in aqueous methanol) at a reduced temperature. To obtain 6c, an aqueous solution of NH3 was saturated with gaseous NH3 with cooling, and then a freshly prepared cooled solution of 5 was added to it dropwise with stirring. 3-Alkyldiaziridines 1dagger;,Dagger; (Table 1) were synthesised at a reduced temperature by passing a flow of gaseous ammonia through the reaction mixture throughout the reaction. 1,3-Dialkyldiaziridines 7 were prepared by the interaction of dagger; Preparation of 3-alkyldiaziridines 1 (general procedure): HASA (0.5mol) was added at ndash;10 to ndash;5 deg;C to a solution of aldehyde (0.5 mol) in water (60ml) (in the case of butyric aldehyde, in 45 ml of water+ 15ml of MeOH), and the mixture was stirred for 15ndash;20min until it no longer reacted with an acidified solution of KI.Then the solution of aldoxime-O-sulfonic acid 5 thus obtained was added dropwise at ndash;20 to ndash;18deg;C to an aqueous solution of ammonia (300g, 47). The reaction mixture was stirred for 8ndash;10 h at 0ndash;2 deg;C with a moderate flow of ammonia being passed through.The mixture was then allowed to stand overnight at 0 deg;C and stirred for 10h at 18ndash;20deg;C under a flow of ammonia. The aqueous diaziridine solution was distilled off using a rotary evaporator into a vessel cooled with dry ice, and the product was distilled three times from solid alkali.For all the compounds 1 synthesised, satisfactory elemental analysis data were obtained. Preparation of 1,3-dialkyldiaziridines 7 (general procedure): A 50 aqueous solution containing a two-fold molar excess of the corresponding primary aliphatic amine was added dropwise to a solution of aldoxime-O-sulfonic acid 5 obtained by the above procedure. The mixture was stirred for 7h at 15ndash;20deg;C and then the product extracted with CH2Cl2.The extract was dried with K2CO3, the solvent evaporated and the residue distilled in vacuo. Dagger; Selected spectroscopic data for 3-alkyldiaziridines. For 1a: 1H NMR (d, ppm, CDCl3): 1.26 (d, 3H, CH3), 2.19 (br. s, 2H, NH), 3.03 (q, 1H, CH); (CH2Cl2): 1.26 (d, 3H, CH3), 1.83 (br. s, 1H, NH), 2.51 (br.s, 1H, NH), 3.02 (q, 1H, CH).For 1b: 1H NMR (d, ppm, CDCl3): 0.94 (t, 3H, CH3), 1.37 (dq, 2H, CH2), 2.17 (br. s, 2H, NH), 2.91 (t, 1H, CH). For1c: 1H NMR (d, ppm, CDCl3): 0.94 (t, 3H, CH3), 1.43 (m, 4H, CH2CH2), 1.72 (br.s, 1H, NH), 2.34 (br.s, 1H, NH), 2.92 (t, 1H, CH). RCHO N N N R R R NH3, NH2Cl RCHO, NH3 NH NH R NH NCH(OH)CCl3 R NaOH PhCOCl NCOPh NCOPh R Cl3CCHOmiddot;H2O/H+ 1 2 3 4 Scheme 1 R=Me, Pr, But RCHO + NH2OSO3H RCH=NOSO3H RCH=NOSO3 ndash; B+ i ii (or iii) NH NH R NR1 NH R iv v 1andash;c 5 6 7andash;c 6a B = Et3NH (ii) 6c B = NH4 (iii) + + + Scheme 2 Reagents and conditions: i, H2O or H2Ondash;MeOH (4 : 1), ndash;10 to ndash;5 deg;C, 15ndash;20 min; ii, Et3N (R1NH2), H2O, ndash;20 to ndash;15deg;C; iii, 47 NH3, H2O, ndash;20 to ndash;18deg;C; iv, ca. 40 NH3, H2O (or H2Ondash;MeOH), 0ndash;2deg;C, 8ndash;10 h, then 18ndash;20deg;C, 10 h; v, R1NH2, H2O (or H2Ondash;MeOH), 15ndash;20deg;C, 7 h. 6b B=R'NH3 (ii) 1a R=Me 1b R=Et 1c R = Pr 7a R=Me, R1 = CH2CHMe2 7b R = Et, R1 =Bu 7c R=Pr, R1 =CH2Ph H2NMendeleev Communications Electronic Version, Issue 2. 1997 (pp. 47ndash;86) primary aliphatic amines with either triethylammonium salts 6a, obtained beforehand, or with salts 6b, prepared by the reaction of 5 with an excess of the same amine, which was used in this reaction (Scheme 2).The yields of 3-alkyldiaziridines 1 were 22ndash;32. The yields of 7 were somewhat higher and comparable with those previously reported in the literature9ndash;11 (Table 1). This work was supported by the INTAS grant no. 94-2839. References 1 E. Schmitz, Chem. Ber., 1962, 95, 688. 2 (a) E. Schmitz and D. Habisch, Rev. Chim. Acad. Rep. Populaire Roumaine, 1962, 7, 1281 (Chem.Abstr., 1964, 61, 4331); (b) H. W. Heine, R. Henrie, II, L. Heitz and S. R. Kovvali, J. Org. Chem., 1974, 39, 3187; (c) E. Schmitz, D. Habisch and C. Grundemann, Chem. Ber., 1967, 100, 142; (d) S. R. Paulsen, Ger. Pat., 1126395, 1962 (Chem. Abstr., 1962, 57, 9875g). 3 E. Schmitz, Trekhchlennye tsikly s dvumya geteroatomami (Three- Membered Rings with Two Heteroatoms), Mir, Moscow, 1970, pp.123, 150 (in Russian). 4 Yu. V. Zeifman, E. G. Abduganiev, E. M. Rokhlin and I. L. Knunyanz, Izv. Akad. Nauk SSSR, Ser. Khim., 1972, 2737 (Bull. Acad. Sci. USSR, Div. Chem. Sci., 1972, 21, 2667). 5 R. G. Kostyanovskii, G. V. Shustov and V. I. Markov, Izv. Akad. Nauk SSSR, Ser. Khim., 1974, 2823 (Bull. Acad. Sci. USSR, Div. Chem. Sci., 1974, 23, 2725). 6 A. N. Mikhailyuk, N. N.Makhova, A. E. Bova, L. I. Khmelrsquo;nitskii and S. S. Novikov, Izv. Akad. Nauk SSSR, Ser. Khim., 1978, 1566 (Bull. Acad. Sci. USSR, Div. Chem. Sci., 1978, 27, 1367). 7 (a) H. J. Abendroth, Angew. Chem., 1961, 73, 67; (b) E. Schmitz, C. Horig and C. Grundemann, Chem. Ber., 1967, 100, 2101. 8 R. N. Keller and P. A. S. Smith, J. Am. Chem. Soc., 1964, 68, 899. 9 A. A. Dudinskaya, A. E.Bova, L. I. Khmel'nitskii and S. S. Novikov, Izv. Akad. Nauk SSSR, Ser. Khim., 1971, 1523 (Bull. Acad. Sci. USSR, Div. Chem. Sci., 1971, 20, 1419). 10 C. Szantay, F. Chmielewicz and T. J. Bardos, J. Med. Chem., 1967, 10, 101. 11 E. Schmitz and D. Habisch, Chem. Ber., 1962, 95, 680. a The IR spectra of all compounds 1 and 7 contained nNH =3220cmndash;1. Table 1 Yields and some physicochemical characteristics of 3-alkyldiaziridines 1 and 1,3-dialkyldiaziridines 7 and their derivatives.a Compound Yield () Bp/deg;C(Torr) (Mp/deg;C) nD 20 Derivative 1a 22 105ndash;107(760) (24.5ndash;25.5) ndash; 1,2-Dibenzoyl 4a, mp 106ndash;108 deg;C (lit.,2c 108ndash;109deg;C) 1b 32 60ndash;61(55) 1.4445 ndash; 1c 22.1 47ndash;49(30) (12.5ndash;14) lit.,2d 45ndash;48(30) 1.4478 Chloralhydrate 3c, mp 116ndash;118deg;C (MeOH) (lit.,2c 116ndash;118 deg;C) 7a 44.0 42ndash;45(20) lit.,9 43ndash;45(20) 1.4260 ndash; 7b 34.0 50ndash;51(31) ndash; Oxalate, mp 108 deg;C (decomp.) (lit.,10 108 deg;C, decomp.) 7c 32.2 106ndash;112(1) (11ndash;13) lit.,11 100ndash;103(0.6) (12ndash;13) ndash; ndash; Received: Moscow, 12th November 1996 Cambridge, 12th December 1996; Com. 6/07747A