Conversion of 1 2-Diols into Aldehydes Induced by Photolysis of Alkylcobaloximes A Model System for Dioldehydrase.код для вставкиСкачать
W R ::;;:; I :o x so, (lc), = to success in the cases of I-benzothiepin l,l-dioxides ( I ,)['I, thiepin l , l d i ~ x i d e [ ~ ~ ,I-benzothiepins and ( I a)12b.41. We have now accomplished the synthesis of 1-benzothiepin 1-oxides ( 1 b). oxides ( 5 ) (in nonpolar solvents) is estimated to lie about 40 to 50°C lower than that of the corresponding l-benzothiepins (4).The half-livesare: ( 5 a ) : 1SS+6 rnin (10"C, CDClJ; ( 5 b ) : S 2 + 2 min (54"C, CDC13); (4a): 180+7 rnin (59"C, CDCI,)['l; (4b): 66&2 min (89"C, CC14)r71. Received: August 25, 1975 [Z 318 IE] German version: Angew. Chem. 87, 843 (1975) CAS Registry numbers: (21. 57458-93-2: (3!> 57458-88-5; i l l ! ) . 37014-56-5; i l h ) , 57458-94-3. / 5 0 ) . 57458-89-6: i 5 h ) . 57458-90-9. ( 6 ~ 1 .57458-91-0: l 6 h l . 57458-92-1 [I] Seven-Membered Heterocyclic Compounds, Part 17.-This  Qy$ H,CO I / J   1 4 ~ ) 1461 .  H,CO 161 0YH5 OR Since it was to be assumed from numerous unsuccessful attempts at preparation that unsubstituted ( I 6 ) is less stable than benzothiepin ( I a ) , R = H, we first prepared the substituted I-benzothiepin I-oxides ( 5 a ) and ( 5 b ) both via the benzothiepinone I-oxide (3) and by direct oxidation of the benzothiepins (4a) and ( 4 b)r4a,4b1(Table 1). Apart from analytical data"', smooth further oxidation to the l henzothiepin 1,l-dioxides / 6 a ) and iCib)[sland 'H-NMR data afford structural proof of ( 5 a ) and ( 5 b ) .  work was supported by the Fonds der Chemischen Industrie. Part 16: ref. [4b]. i s R. F . Lout,, J. Org. Chem. 26, 2728 (1961); 29, a ) c' J . T r u ~ i ~ r land 366 119641: , , bl, H. Hotmunn and H . !4'rs/eriiuchrr, Anrew. Chem. 78. 980 (1966); Angew. Chem. Internat. Edit. 5, 958 (1966): Chem. Ber. 102, 205 (1969). W L. M o c k , J. Am. Chem. Soc. KY, 1281 (1967). a ) H. Hofniunii, B. Mewr, and P. Hofniann. Angew. Chem. 84, 477 (1972); Angew. Chem. internat. Edit. / I , 423 (1972); b) H. H~fmuiin. I f . - J Huhrrstroh, B . A p p l r r , 8. M e w r , and lf. Hrrrrrich. Chem. Ber. /OR. 3596 (1975); c) D. N . Rrrii/io~rdrand C . G. K o i i i v e i i l ~ o v ~ ~J i.i ,Chem Soc. Chem. Commun. 1972. 1232; d ) c' .I. 7?uriidi.s, E ~JshihaLvu,J. C. Sih. and L. J. Miller, J. Org. Chem. 38. 3978 (1973); e) J . M u r u i u , 7 Tutsuoku. and J . Sugihuru, Angew. Chem. 86, 161 (1974); Angeu. Chem. internat. Edit. 13, 142 (1974). Correct elemental analyses were obtained for all new compounds The ( = [ M - S O ] + ) as mass spectra of ( 5 u ) and ( 5 6 ) contain [M-48]' the base peak, while the mass spectra of the considerably more stable sulfones ( 6 u ) and (66) contain the nonfragmented molecular ions. W S/eg/ichand G. Hour, Angew. Chem. 81, 1001 (1969); Angew. Chem. internat. Edit. 8, 981 (1969). R. Heidrich, Diplomarbeit. Universitat krlangen-Nbrnberg 1975. Conversion of 1,2-Diols into Aldehydes Induced by Photolysis of Alkylcobaloximes: A Model System for Dioldehydrase[**] By Bernard 7: Golding, Terence J . Kernp, Enrico Nocchi, and William P . Watson[*] 5'-Deoxy-5'-adenosylcobalamin(AdoCbl) acts as a coenzyme for the conversion of certain 1,Z-diols into aldehydes catalyzed by the dioldehydrase of Aerobacter aerogenes"! In these reactions enzymatically-induced homolysis of the cobalt-carbon bond of AdoCbl is followed by attack of the Table I.Preparation of 1 3 ) . ( 5 a ) , ( j h ) , ( 6 ~ )and . (6h). Cpd. Preparation 'H-NMR [a] Yield [''lo] M.p. i ('1 (31 (5u) (56) (6u) (66) from ( 2 ) ; with m-chloroperbenzoic acid (molar ratio 1 :I)in CH,C12, 12 h at -20°C [b] from(3):with AcZO/Et,N/p-dimethylaminopyridine,24hat -30"C:precipitated from CH,C12 at -20°C with light petroleum from ( 4 u ) : with in-chloroperbenroic acid (molar ratio I : 1 ) in CH2CI,, 5 b at -20°C [b] from (3): with K O t B u h e t h y l fluorosulfate in THF, 5 h at - 120°C [c] from ( 4 h ) : with in-chloroperbenroic acid (molar ratio I : I) in CH,Cl,, 1 2 h at -20°C [c] from ( 5 ~ ) as : for ( 5 h ) from ( 4 b ) from ( 4 ~ ) with : in-chloroperbenzoic acid (molar ratio 1.2) in CH,CI,, 1 2 h at -25°C from ( 5 h ) . as for ( 5 6 ) from ( 4 h i from 1 4 h ) . as for ( 6 u ) from ( 4 a ) 3.85 95 71 I32 72 (dec ) 4.61 3.37 3.96 89 86 80 85 85 70 81 105 I52 142 [a] 2-H (s); CDC13, T values in ppm. [b] Precipitated with light petroleum [c] Crystallized from methanol. Expectedly, ( 5 a ) and ( 5 b ) are thermally less stable than the parent I-benzothiepins (4a) and ( 4 b ) . O n warming in an inert solvent they readily eliminate SO to form the naphthalenes ( 7 a ) and ( 7 b ) respectively[4h1without formation of any further reaction product being detectable in the 'H-NMR spectrum. From a comparison of the half-lives for thermal decomposition of ( 5 a ) and ( 5 b ) with those of ( 4 a ) and (4 b), respectively, the stability range of I-benzothiepin 1- [*I I'[ Dr. B. T. Golding [ '1. Dr. T. .I. Kemp, Dr. E. Nocchi. and Dr. W. P. Watson Department of Molecular Sciences. University of Waruick Coventry CV4 7AL (England) T o whom correspondence should be addressed. [**I Financial support was given by the Science Research Council (to M! P. M:) and by the Academia Narionale dei Lincei (to E . N . under the auypices of the Royal Society European Exchange Scheme). -We acknowledge excellent technical assistance from L. C Curr and C . ,Yonn. 813 resulting 5'-deoxy-5'-adenosyl radical on the substrate (SH) giving 5'-deoxyadenosine and the radical S*.The latter is somehow transformed to radical P' which abstracts a hydrogen atom from 5'-deoxyadenosine, thereby regenerating the 5'deoxy-5'-adenosyl radical and producing a 1,I-diol (PH), from which product aldehyd? arises[21. similar reactions which ensue followWe have pointed ing attack of hydroxyl radicals on 1,2-di0ls[~l,e . g . : HOCH,CH,OH - OH H O C H ~ ~ H OH+ (a) H z 0 + *CH,CHO An even more compelling model system would achieve the nonenzymatic formation of an aldehyde from a 1,2diol with the help of an alkyl radical R' derived from an alkylcobalt compound like AdoCbl: R ~ C H O H C H ~ O-% H - R~CHOHEHOH H-atom H,o + R ~ ~ H C H O (b) R'CH,CHO acetic acid in the presence of oxygen, only a trace of pentanal was obtained (50.5 % yield). The main product derived from the 4,s-dihydroxypentyl group of (2) in anaerobic photolyses was 1,2-pentanediol ( N 50 % yield). We propose that pentanal arises as follows in the anaerobic photolysis of (2): Photoinduced homolysis of the Cobond of (2) gives the 4,s-dihydroxypentyl radical which mainly becomes 1,2-pentanediol, but partly undergoes a specific hydrogen transfer (favored by a six-membered cytlic transition state"]) to generate the radical n-C3H7CHOHCHOH; acidcatalyzed re~rrangementL3~ 4a1 of this radical can give the radical n-C3H ,CHCHO which produces pentanal after a hydrogen atom abstraction (from a source to be determined). Although enzymatic reactions involving dioldehydrase and AdoCbl are not photochemically inducedt8],we submit that the clean, rapid photohomolysis of alkylcobalt compounds justifies the use of photolyses in model experiments. We predict that the 4,5-dihydroxypentyl radical plays a similar role to the 5'-deoxy-5'-adenosyl radical in the enzymatic system, by performing a selective hydrogen atom abstraction on a 1,2di0l[~1. \""me We now report our experiments in the pH range 2-3, which apparently demonstrate transformations of the type in eq. (b). A de-aerated solution of methyl(aquo)cobaloxime ( (4mM)in aqueous KCI/HCl buffer (pH 2.0) containing 1,2-ethanediol (1.0 M) was photolyzed [h= 380+ IS nm, chargetransfer band of (Z)]. The disappearrince of ( I ) followed the classical form [IT(- 1)=0.14+0.01] giving Co;:, free ligands, and acetaldehyde [isolated as its 2,4-dinitrophenylhydrazone: yield N 10 % (estimated by NMR spectroscopy); 5 % isolated]. No acetaldehyde was produced in reaction mixtures kept in darkness for the duration of photolyses (45 min)16].The yield of acetaldehyde given is based on cobaloxime and is 250 x lower when related to 1,2-ethanediol. This is evidently due to the low probability of intermolecular attack of methyl radicals on 1,2-ethanediol and/or to the lack of ?n efficient chain process emanating from the radical HOCH,CHOH. As the concentration of 1,2-ethanediol increases, so does that of acetaldehyde, presumably due to the increasing efficiency of the captur: of methyl radicals with production of the radical HOCHzCHOH and hence of acetaldehyde (cf. eq. (a) and refs. [4a, 4cl). Received: August 13. 1975: in abbreviated form: September 2, 1975 [Z 312 IE] German Qersion:Angew Chem. 87. 841 (1975) CAS Registry numbers: Methyl(aquo)cobaloxime, 25360-55-8; 1.2-ethanediol, 107-21-1 ; acetaldehyde, 75-07-0: 4.5-dihydroxypentyl(pyridine)cobaloxime, 57031-36-4; pentanal, 110-62-3 Cf. H. A. Burkw, Annu. Rev. Biochem. 41, 55 (1972).  T H. Finlay, J . Vulinskr, K . Saro, and R. If. Abdes, J. Biol. Chem. 247, 4197 (1972).  B. T Goldrrzy and L. Rodo~ii,J. Chem. Soc. Chem. Commun. IY73. 939.  a ) B . C. Gilbwt, J . P . Lorkin, and R . 0. C. Norriian, J. Chem. Soc. Perkin II 1972. 794: b) K . M . Bunsol. M . G r U r A A. Hrrrgkin, and E . Joriufn, J. Phys. Chem. 77. 16 (1973):c) C Wdlizq and R A. Johri\o~i. J. Am. Chem. Soc. 97, 2405 (1975).  Alkyl (base)cobaloximesare bis(biacetyldioximato)cobalt complexes with a o-alkyl group and a Lewis base as axial ligands, used as models for alkylcobalamins [cf. C . N . Sc/ir.arrzer, Acc. Chem. Res. 1, 97 (196X)l. Syntheses of ( 1 ) and ( 2 ) : B T Golrliiig ef a/., to be published  In the control experiments mentioned, 20.2"4 yield (based on cobaloxime) of acetaldehyde or pentanal would have been detected.  J . W Wilt in J . K . Kodii: Free Radicals. Wiley-lnterscience, New York 1973. Vol. 1. Chap. 8, p. 380 [S] See, however. T Yumane. S. Shiiiii;ii, and S. Firkui, Biochim. Biophys. Acta 110, 616 (1965).  IA-Hydrogtn transfer in the 4.5-dihydroxypentyl radical giving the radical n-C3H , C O H C H 2 0 H , followed by acid-catalyzed rearrangement""'. would yield 2-pentanone which was not detected after photolysis of (21. [l] Thermal Cycloaddition between 3,6-Dijhenyl-s-tetrazine and 9-0xabicyclo[6.1.0]nona-2,4,6-triene; Construction of the Oxonino[4,5-d]pyridazine Frame[**' By A . G. Anastassiou and S . J . Girgend'] 4,5-Dihydroxypentyl(pyridine)cobaloxime (2)[51 contains both a 1,Zdiol and potential alkyl radical; hydrogen atom transfer between radical and diol can then bc nn intramolecular process. Photolysis (h= 380+ 15nm) of a de-aerated solution of (2) [ 3 . 5 m ~ ]in 0.1 M aqueous acetic acid (pH 3.0) gave pentanal [isolated as dinitrophenylhydrazone in 3.5 k0.3 % yield (three experiments)]. Control experiments performed in the dark [storing the following compounds in 0.1 M acetic acid : (2) (3.5 mM); 1,2-pentanediol (3.5mM); 1,2-pentanediol ( 2 . 8 m ~ and ) cobalt(ii) acetate ( 4 m ~ ) ]gave no detectable pentanalLh1. Photolysis (h=380* 15 nm) of a de-aerated solution containing biacetylglyoxime (7 mM), cobalt(1r) acetate (3.5mM), and 1,2-pentanediol (3.5mM) in 0.1 M acetic acid also gave no pentanal''! When (2) was photolyzed in 0.1 M 814 In an attempt to extend the scope of the pericyclic synthesis of novel n: systems[" to molecules containing more than one heteroatom we examined the synthetic potential ofdiphenyltetrazine (2)[" as a pericyclic trap of properly structured molecules. In this report we briefly describe the use of (2) in the first successful thermally activated cycloadditive trapping of 9-oxabicyclo[h.l .O]nona-2.4,6-triene (1) to produce an oxa[*] Prof. Dr. A. G. Anastassiou and S. J. Girgenti Department of Chemistry, Syracuse University, Syracuse, New York 13210 (USA) [**I We thank the National Science Foundation (GP-38553X)and the Petroleum Research Fund, administered by the American Chemical Society. for support of this work.-We should also like to express our appreciation to Mr. L. MrCmdless for the determination of the IOOMHz spectra.