Photolyses of N-Nitrosamides in Acidic and Neutral Media

PHOTOLYSES OF N-NITR OSAMIDES

IN ACIDIC AND NEUTRAL MEDIA

Antonio Chun Hung Lee

B.Sc., The university of British Columbia, 1958

A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF

THE REQUIREMENTS FOR THE DEGREE OF

MASTER OF SCIENCE

in the Department

Chemistry

ANTONIO CHUN HUNG LEE , MON FRASER UNIVERSITY

April, 1967 B.Sc., The University of &ritish Columbia, 1958

in the Department of Chemistry

'Je accept this Thesis as conforming to the required standard. PARTTAL COPYRIGIIT LICENSE

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2hotolyses of several IT-i~itrosanides in acidic end neutral media were studied. .:he photochenical decomposition of J- nitrooanides was fouud to involve exclusively nitrogen-nitrogen bond cleavage of the 1:-nitrosarnide group in contrast to the pyrolytic decomposition which involved cleavage of the acyl nitrogen bond. in acidic media, photolyses of IT-nitrosanides led to the light catalyzed denitrosation of the N-nitrosanides by photo- elimiiiation of the [NGH] group with the forxation of allylidenimides. The alkylidenimides undervent secondary reactions to give the corresponding aldehydes. The photoelimination products were identified as the 2,4-dinitrophenylhydrazones of the aldehydes.

In neutral media, the primary photolytic process of ii- nitrosa.:iides was the,fomation of nitroso and anide radicals. The axide radical was found to abstract intranolecularly a hydrogen atom attached to the carbon atom in the 5-position # to give a $-carbon radical. This 5-carbon rzdicel then coupled rniJ~hthe nitroso radical to give a C-nitroso compound which either tautonerized to i'om oxiine or dimerized. Alternatively the arnide radiczl underwent elinination of an alpha hydrogen to give the alkylidenimide as an intermediate. iThe $-position was numbered in reference to the nitrogen atom o; the ar~idegroup. For exzmi~le,- - the for-.ula of 6-nitroso-n- 41 hexylf onamide would be CR3-CH2-F-CH2-CH2-CH2-:;H-$-;; N=O 0 iii

In presenting this thesis in partial fulfillinent of the requireinents for an advanced uegree a-L the Sixon Fraser University, I agree that the Library shall make it fully available for reference and study. I further agree that permission for extensive copying of this thesis for scholarly purposes may be granted by the Iiead of my Departraent or by his representatives. It is understood that copjing or publication of this thesis for financial gzin shall not be allowed without my written pemission.

2epartment of Chemistry ...... The Sixon Fraser University aurnaby2, BOGo, Canada

Date...... I would like to express my sincere thanks and appreciat- ion to Dr. Y.L. Chow for his advice and encouragenent throughout this research. It is a pleasure to thank Drs. 'J.A. Ayer and D.D. Tanner of the University of Alberta for providing the mass spectra. The co-operation of Liss ?,I. 3ieser of this department in providing the n.m.r. spectra is deeply appreciated. 6 . Cyclohexylacetamide ...... 8 7. Phenethylacetamide ...... 8 8. N-nethyl-o-toluamide ...... 8 9 . Benzylformamide ...... 9 10 . 4-Phenyl-n-butylacetsmide ...... 9 11 . ?ieserVs Solution ...... 10 C . PHEPAMTIOWS GP N.TU'I'I'HOSAi.IIDES General Procedure for Kitrosation of Amides ....11 Preparations of h-nitrosoacetamides and N-nitrosoformamides ...... 11 D . PKGTOLYSES IN ACIDIC XdDIA General Procedure of Photolysis in Acidic Ledia vi

'l'Ai3LI;S 01' CO?:T~5:'I'S (Cont Id ) Pa ge 4. N-nitroso-N-pheiiethylacetamide ...... 17 5 . N-nitroso-IT-cyclohexylacetamide ...... 18 uf . N-nitroso-N-n-butylformamide ...... 18 E . PXOTOLYSdS IK UNJ'L'IUL I3ZDIA Generzl Procedure of Photolyses in IJeutral ; edia .. 19

4. N-nitroso-14-benzylacetamide ...... 28 5 . N-nitroso-N-pheiiethylacetamide ...... 29 6a . N-nitroso-N-methylcaproamide in n-pentane ...... 29 6b. N-nitrooo-N-methylcaproamide in cyclohexane ...... 31 6c . F-nitroso-3-methylcaproamide in petroleum ether ..31 7a . N-nitroso-X-methyl-o-toluamide in petroleum ether ...... 32 7b . N-ni$roso-N-methyl-o-toluamide in benzene ...... 35 8. Control Photolysis ...... 38 I11 . RESULTS Photolyses in Acetic Kedia ...... 39 Photolyses in Xeutral Xedia ...... 41 DISCUSSIONS Pliotolyses of lj-nitrosamides in Acidic Iiledia .....52 Photolyses of X-nitrosanides in Neutral +:edia ....54 SUGGESTIDIS FGR 3'U;iTIIER ~i'Sdb3CH ...... 60 BIBLIOGRAPHY ...... 64 vii

Acidic Liedia ...... 61 111. The l-'roducts of Pliotolyses of N-nitrosamjdes in

Cliart s -Paqe I. The Therxal Decomposition of IJ-nitrosanide ...... 1 11. The Photocheinical Iiechanism of ?I-chloramides ...... 2 111. The Yhotochenical Rearrangement of IT-chlorimides ...... 3 IV. The Photolysis of Xitrite Ester in Xeutral Eedia ...... 3 V. Possibility of Generating Xitrogen 2adicals .from the Photolysis of 2:-nitrosanides in lleutral ILedia ...... 4 VI. Photo-elinination of [zc~]from I<-nitrosacine ...... 4 , VII. The Photolysis of N-nitroso-B-benzylacetm-ide in Neutral Iiedia ...... 40 VIII. The Photolysis of N-nitroso-N-n-hexyl2cetanide in Neutrl LIedizl and the iiydr01ysi.s of C-ilitroso Dir.er .... 43 IX. The Phot olysis of i!-nitroso-i~-4-~hen~l-n-&ut~laceta:?Iide

in Keutral Lledia and the Formation of 2-cheiiyl- pyrrolidine ...... 45 X. The Cleavege of the ~-oximino-il-hesylfor~:~a~~i~eubon Electron Impact ...... 45 XI. The Photolysis of K-nitroso-W-phenethylco,cei;a::lciein Xeutrzl L!edia ...... 47 XII. The Photolysis of X-nitroso-3-nethylc8proan1ide ...... 4s viii

Charts (Cont 'd) Pa ~e XIiI. The Photolysis of 1:-nitroso-N-methyl-o-toluanide in Xeutral Media ...... 51 XIV. Xechanism of the Photolysis of N-nitrosamides in Acidic Xedia ...... 53 XV. General .Photochemical Xechanisrn of N-nitrosamide in Xeutral Xedia ...... 55 XVI. Possible Side Reaction of the Photolysis of

Figure I. The n.m.r. Spectrum of Compound ;(;;";XI1...... 49 lTlie N-nitrosanides are characterized by a series of absorptions at 390-430 rnp in either polzr or non-polar solvents. They are thermally unstable. Their thermal stability is depend- ent on the structure of the parent amines (X group in conpound

The 2:-nitroso-N-alkylamides were first pyepared by ?echmann (2) in 1894 and by Chancel (3) in 1895. Chancel and latter Peclunann(4) reported that the decomposition of bl-nitrosamides yielded esters, but neither studied the recction any further. E.H. 'Xhite (5) uindertook further study of the thermal decomposition of if-nitrossmides to esters in various solvents ranging from acetic acid to cyclohexane. On the basis of these studies, he proposed that N-nitrosamides rearranged to form intermediate diazoesters which underwent nitrogen elimination to yield the carboxylic ester. In this mechanism, the nitrogen-carbonyl bond cleavage took place as the first step (6).

Chart I. The Thermal Decomposition of IT-nitrosamide.

Although investigations of photochenically labile conpounds such as B-halamides (7), N-chloroimides (8) and alkyl nitrite esters (9) have been comprehensive, no work has been done on 2 the pilotolyscs of X-ixi Lrosmides.

T - 2. S. Xeole , s .L, iiarcus and ii. G. Sclieperr: reported that -- A-ciiloro derivatives of both f!-methyl and N-t-butgl pentano- anides were rearranged upon irradiation to the 6-chloro isomers in benzene (7). The N-chloroamide rearrangements m-re found tobe a free-mdlcal chain process since the chloroaxidec rearranged rapidly but only upon weak irradiation. The photochexical inechanism of X-~hloroa.~lideswas found to be as following. - Chart I1 The Photochemical ;.;echani.sm of Z-chloroznides- .

3.C. Peterson and A, '.'!anbs~ans (8) reported i~hota- chemical rearrzngenent of 3-chloroimides to 5-chloroinides. d IY Acyclic inidyl radicals such as (ZDOCB3 ) might rezrranse to X at rates Past enough to permit selective introduction 1 Bi <- - of functions1 groups at the 6-position of the inides. ?he 1;-chloroifiide3 VIII having primzry, secondary or 'oenzjilic hydrogen do 2f ford their 6-chloro isoaer when iyradizted in neutral organic meaia. Chart III

The Photochemical Rearraju-;ement of 1:-chloroimides-.- .

The photochemical generation of amide radicals from X-chloroamides and of irnide radicals from 2-chloroimides appeared to follow the same mechanistic pathway as the Barton . . reaction (10). i'he Barton reaction involving the photolyses of suitably constituted organic nitrite ester in toluene results in an intramolecular exchange of the IiO of the nitrite residue with a hydrogen atom attached to a carbon atom in the $-position from the amide nitrogen. The C-nitroso compound thus formed could be isolated 2s the corresponding nitroso dirners or, after tautomerization, as the oximes.

Chart IV The Photolysis of Nitrite Ester in Neutral Liedia. /H /I1 "0, CH2 0-NO A" CX2 O* 6~~ 0-H CB, OH Pu + .NO---*u +.~Jo+- (~11) (XIII) (XIV ) (X'J )

The mechanism of irradiation of nitrite XI1 leading to XV involved three steps: first, the photochemical cleavage of the 0-N bond to furnish the zlkoxy radiazl XI11 and *EG; second, the intrainole cular abstraction of hydrogen to furnish the alkyl radical XIV; and finally, the combination of XIV with .XO to furnish the product XV. A further possibility of generating useful nitrogen 4 radicals, by c?nalogy to the photolyses of U-chloroanides, N-chloroimides and nitrite esters was the photolysis of E-nitrosarnides in neutral media.

Chart V Possibility of Generating Eitrogen Radicals frw the Photolysis of nT-ni trosamides in ITeutral I:edia. 0

Unlike the Barton reaction, the photolysis of 1;-nitrosamine in acidic media (11) studied by Chow and his co-workers involved the photoelimination of [NOH] . The photoelimination of [iioa] was shown in the following chart.

Chart VI

Photoelimination of [XOH] from 14-nitrosamille. H P 1

It wa's therefore of interest to investigate the photochemical behaviour of the G-nitrosamides in acetic and neutrel media in order to afford comparisons with the mechanisms mentioned above. A . CEX Z 1x4 L Infrared spectra (i.r.) were obtained with a Perkin- Elmer 421 Infra-cord spectrophotoneter with frequencies listed in cm-l; w = weak, n = medium, s = strong. Spectra were obtained on nujol mulls or carbon tetrachloride solution of solid samples or on neat liquids using sodium chloride optics for all samples.

Ultraviolet spectra (uv) were taken on a Cary 14 Spectrophotometer or on a Unicam SP 800 Spectrophotorneter with wavelength listed as ~2:~~+ . The uv spectra were obtained using a 1 cm quartz cuvet. Xuclezr ;.;apetic Resonance spectra (n.m.r.) were tzken on a Varian A-60 or A 56/50 spectrophotometer; the coupling constant (J) is given in c.p.s., the resonance frequencies given in t based on tetranethyl silane as the internal stand~rd.The solvents used were carbon tetrachloride, deutero-chloroform, dimethyl sulfoxide or acetone as specified. Resonance peak multiplicity is reported in the following manner: s = singlet, rn = multiplet only partially resolved, d = doublet, t = triplet, q = quartet and qu = quintet . Xass spectra (a. s. ) were taken with a Xetropolitan-Vickers i.:S-311 or :JS-g mass spectrometer at the University of Alberta, ddnont on. PTicroanalyses were done by Dr. Dassle of 5757 Tlecelles Ave. , TvUontreal,and by Alfred Rernhardt , Vkx-Planck Tnstitut f& Kohlenforschung , Yulheim (~uhr), Best Germany. Column chromatography was done on neutral alumina, 'Jloelm Rrockman neutral alumina or on silicic acid (Mallickrodt). Thi n-layer chromatography (T.L. C. ) was done on plates of alumina oxide (~amag)which were prepared with the Atahl apparatus. All chemicals used were of reagent grade and used without purification unless otherwise specified. 1. n-3utylz.ce-t anide was prepared by refluxing n-butylamine (36.5 g) with acetic anhydride (365 ml) followed by distillation at reduced pessure (14g0/39 mm) to give 38.89 g of the acetamide. i.: 1650(s), 1555(s). n.m.r.: g.l(t, J=6 c.~.s., 3H); 8.5(m, 4x1; 8.07(s, 3Ii); 6.8(q, J=6 c.p.s., 23);

2. Genzylacetamide v;as prepared by zdding acetic anhydride (102 g) dropwise to benzylanine (53.6 g) in an ice bath with vigorous stirring. The solution was refluxed for one hour and then distilled at reduced pressure. The distillate collected at 198-200•‹/17 rn soon solidified as white needle-

2.77(s, 513).

3. n-Iiexylzcetamide was prepared as described above for n-butylacetamide.,The acetamide was collected by vacuum distillation at 139'/9 mm. i:3280(s), 1645(s), 1550(B).

n.m.r. : g.l(t, J=5 c.p.s., 33); 8.65(m, 8H); 6.7(sY3H); 6.7(q, J=5.5 c.p.s., 2H).

4. n-Butylf ormanide was prepared by ref luxing n-butylaine (36.2 g) with 90 75 formic acid (76.6 g) for 1; hour. The 8 n-butylfomamide was collected by vacuum distillation at 122-125 O/9 (36.2 g) . i:324O(s), 2ri50(w), l65O(s), 1540(s).

n.111.r.: 9.l(t, J=6 c.P.G., 3H); 8.35-8.8(m, 41:); 6.73(q, J=6 c.p.s., 2H); 1.95(b.s., 1H). 5. n-:;exglformarnide was prepared in the same manner as in (4). The n-hexylformanide was collected at 142-146O/9 n~. i.: 3290(s), 2750(w), 1660(s), 1540(9), n.m.r.: 9.l(t, J=5 c.P.s., 3H); 8.4-8.8(m, 6i-1); 6.69(q, J=6 c.p.s., 2B); 1.72(b.a., 1H). 6. Cyclohexglacetanide was prepared in the sane manner as described above for n-butylacetamide. The cyclohexylaceta~ide wzs collected from vacuum distillation at 245O/9 mn. The distillate soon crystallized and was recrystallized from 95 %

7. phenethylacetamide was prepared as in procedure 2. The distillate was collected at 173-176'/13 mm and was re-distilled to give pure phenethylacetamide at 167-170~/10 mm. The distillate crystallized, m.p. 44-45•‹C. i:3290(s), 1645(s), 1540(m), 752(s), 705(s) n.m.r.: -8.15(s, 3H); 7.24(t, J=7 c.p.s., 2H); 6.69(t, J=6 c.p.s.); 2.86(s, 514).

8. iT-xethyl-o-toluenide was prepared by bubbling gaseous methylamine into an ether solution (500 ml) of o-tolyl 9 chloride (70.0 G) until the solution was alkaline to moist litmus paper. The ~ihitepowdery methylamine hydrochloride precipitate v!as removed by f iltration. 'Yhen the ether v~zs removed from the filtrate, a solid compound was obtained. It was recrystallized from ethanol and water to give 51.9 g of white needles, map. 74-75'. i:3360(~), l638(s), 1602(~),l55O(s), 785(s), 720(s), 695(m). n.m.r.: 7.77(s, 3~);7.33(d, J=5 c.p.s., 3H), 2.93(m, 4111, 9. Senzglfornamide was prepared in the usuel rnznner as described above. The distillzte collected at 180-18j0/12 rn2 soon solidified on cooling to give a white solid, m.p. 55-56'. i.: 3270 (m), 2860(m), 1635(s), 1530(m), 740(m), 700(d, 1i.m.r.: 1.94(b.s., 1K); 2.78(s, 5H); 5.7(d, J=6 c.P.s., 2H).

10. 4-Pheny1butylacetami.de was prepared by refluxing the 4-phenylbutylamine with acetic anhydride. The former was obtained by the lithium aluminum hydride reduction of phenylbutyronitrile as described below.

To a solution of lithium altminum hydride (12.86 g) in anhydrous ether (50 ml) in a litre three neck flask, phenylbutyronitrile (25 g) was added dropwise at 0•‹C with stirring. The solution was refluxed for 48 hours. Ice water (15 nl) and sodium hydroxide solution were added dropwise to decompose the unreacted lithium aluminum hydride. The hydrolyzed 10 solution wzs allowed to stand for 2 hours at room texperature, after which time the clear supernatant solution mas decanted. The residue was extracted a few times with ether. The ether extract and the decanted supernatant solution were combined. The ether was removed from the combined solution to give

22.5 g of phenylbutylamine as a pale yelloiTi liquid. i..: 3450(m), 3380(m), 1610(m), 1595(m), 1550(m), 698(~),748(~). This wine (15.4 g) was refluxed in acetic anhydride (30 g) Tor one hour. The excess acetic acid was removed by distillation at 117-118•‹C. The 4-phenylbutylacetanide (16.44 g) was collected at 195-204'/9 rnm. i..: 34OO(m), l66O(s), 1603(~),1560(m), i'l4(rn), 695(s). 11. Pieserts solution (12) was prepared by dissolving 20 g of potassium hydroxide in 100 rnl of water. Sodiuin antra- quinone k-sulfonate (2 g) and sodium hydrosulfite (15 g) were then added with stirring until a clear, blood-red solution was obtained. The solution was used after it was cooled to room temperature. 11 C. PHXPARATJON OF N-NTTROSAP IDES. General Procedure for Nitrosation of Ami.des. The amide was dissolved in a mixture of acetic anhydride and glacial acetic acid. The solution was kept at O•‹C in an ice bath. An excess of granular sodium nitrite was added, in small portions, to the solution during a period of 5 hours with constant stirring. The solution was then stirred for an addi tional 2 hours. The solution was poured into ice water and extracted with ether. The ether extract was washed with 105 sodium carbonate to remove the acetic acid until the pH of the aqueous layer was ca. 8. The ether layer was washed with a small amount of ice water and then dried with anhydrous magnesium sulfate. The ether solution was filtered and ether was removed from the filtrate by rotary ev~poratorat a low temperature to give the N-nitrosamides as yellow liquids or yellow solids. Preparations of I?-nitrosoacetamides and FT-nitrosoformamides. The K-nitroso-N-n-butylacetamide, N-nitroso-N-n-hexylacetamide, N-nitroso-IT-benzylacetamide, N-nitroso-IT-aethgl- acetamide, N-nitroso-N-phenethylacetamide, N-nitroso-B-methylcaproamide, N-nitroso-N-benzylformamide were prepared in the same manner as described in the above procedure. Their characteristic i.r., n.m.r. and uv absorptions are listed in Table I. The N-nitroso-If-methylacetamide, for example, has n+x* absorption peaks at 376 (€=l88), 390 (€=274), 426 (~=460) and x-tx* at 276 mp (6=3,780) in cyclohexane solution. In methanol solution, it has absorption peaks at 375 (6=77),

389 (&=log), 405 (t=142), 424 (6=142) and 237 my (C =9,800).. . Table I

The i.r. znd n.m.r. Spectral Characteristics of the :;-nitrosanides. IT-nitroso- i.r. n.m.r. uv ecetmidcs (cn-l) CH3C0 -CH,N- Solventa Absorption Peaks L

11-Cyclo- 1720, 8.01 5.32(m) hexyl 1510 Table I (contld)

i.r. 1i.rn.r. (c) U-J (cm-l) CB, -il-Ci-I, Solvents Absorption Peaks 2 2 0-Toluyl- 1715, 6.84(s) 7.8(s) Petrolem 390, 407, amide 1513 Xther 426 (man. ) Caprcyl- 1725 , 9 .09(t, 6.90(s) Cyclo- 376, 390 408 amide 1500 J=Gc.p.s.) hexane 427 (mzx. 1

N-nit roso- i.r. n.m.r. (t) uv forinamides (cm-l) -COX -UGH.,- Solvents Absorption Peaks L 14 11. Pi;CTOLYSaS IN ILCIDIC :.;,

axount of 3r3dy1s reagejnJi, was added TO 5C) LI.L 02 ;;L?tl.il.:,-;i!. 1.2:~

to give a yellow crystalline 2,4-dlaitrophenylhydr8zone (720.3

ng, 35 ;j yield) which was recrystallized Cron aqueous ethanol to give yellow needles; n.p, and mixed m.p. with the 2,$-

dinitropl~enylizydrazoneof the authentic n-butanzl, 118-121' C (lit. 122') (13). TLe distillation of the renaining solvent gave a brown residue (879.1 mg, 45 yield) which was purified by washing with 20 % sodium carbonate solution followed by ether extraction and vacuum evaporation to give a liquid. The i.r. aiid n.m.r. spectra of the liquid were identical with those of an authentic sample of n-butylacetarnide. 2rom the other half of the distillate, the dixethone

derivztive ves prepred. 2S0i~t4- g of ~leth~i~~:72s 2rlr1.ed tc the rexaining distillate. The solution was then refluxed for half an hour. On cooling in an ice bath, white needles of the dizethone derivative of n-but anal were obtained which were recrystallized from 50:; aqueous ethanol, m.p. 131-133OC (lit. 134') (14). 2. ;;-nitroso-1;-n-hexylacet a~~lide.

The 1;-nitrosamide (3.44 g) was photolyzed in solvent A

(200 ml) with 2 100 watt Xanovia lamp. The photolyzate was 0 distilled under ataospheric pessure to give a brolwn residue 2nd a distillate (100 ml). No 2,4-dinitrophenylhydrazone was obtained when the distillate was treated with a calculated amount of the Srady's reagent. Treatment of the residue 16 (one-third) with Urady's reagent gave yellow needles (165 ng, 9.1:;) which were recrystallized from ethanol-water mixture ; n.p. and mixed map. with the 2,4-dinitrophenylhydrazone of authentic n-hexanal , 103-105 '(lit. 104' ) (15) . The remaining residue was extracted with ether which was washed with 10.6 sodium carbonate and then water until the aqueous layer was neutral. The i.r. spectrum of the brown liquid obtained from the ether extract was virtually the same as that of an authentic sample of the n-hexyl acetamide except for very weak peaks at 1725 and 1280 cn-I which were attributed to n-hexylzcetate. 3. 17-nitroso-N-benzylacetmide.

The 1;-nitrosamide (3.677 g) was photolyzed in solution

A (206 ml) for 40 3/4 hours with a 100 watt Hanovia lanp. The photolyzate was distilled at 30-31•‹/9 mm to give 147 ml of distillate and a residue. The residue was taken up in water and extracted with ether. The ether layer was washed with 20% sodium carbonate and then with water until the aqueous layer was neutral. Uhen the ether was evaporated, a brown residue (1.7 g) was obtained. A part of this brown residue

(0.3 g) and hal? of the distillate were reacted separately with Bradyls reagent to .give the 2,4-dinitrophenylhydrazone derivative of benzaldehyde (combined yield 77$) which was recrystallized from ethyl acetate; m.p. 239-242'; mixed m.p. with an authentic sa,nple of the 2,4-dinitrophenylhydrzzone of benzaldehyde, 240-241.5•‹C. The aqueous layer from ether entract was evaporated to give a brovm residue. Sublimation 17 of the residue under vacuum gave white needles. The i.r. spectrum of these needles was superimp~aablewith that of an authentic sample of acetamide.

In a separate experiment the Il-nitrosamide (5.54 g) was photolyzed in solution B (200 ml) a 200 watt lianovia lamp. Half of the photolyzate was reacted with 3rady1s reagent to give the 2,4-dinitrophenylhydrazone of benzaldehyde (1.6 g) which was recrystallized from ethyl-ethanol mixture, mop. and mixed mop. with an authentic sample of the 2,4-dinitrophenylhydrazone of benzaldehyde was 241-243•‹C. Tkle solvent from the other half of the photolyzate was removed to give a brovm liquid (3.89 g), 1.64 g of n2s chronatographed on neutral alumina. Slution with 10:; chloroform in benzene gave benzylacetzmide (616 mg, 583;), the i.r. and n.m.r. spectra of which were ideatical with those of an autilentic sample. Elution with chloroform gave white needles (320 mg, 19.5;) which were identified as 1,l-diacetamido- toluene. These crystals were recrystallized from an acetone- benzene mixture, mop. 246-247OC. ire 3270(s), 1660(s), 1520(w) n.m.r.: 2.66(s, 5H); 5.24(s, ca.lH); 8.03(s, 6H); impurity at ca. 7.9. Analysis Calcd. for CllH14N202: C,64.06$; ~~6.84';; N,13.58$. Found: C,64.44; H,7.36; 1;,13.27. 18

The N-nil;rosamide (4.95 ;.;) was photolyzed in solution 3 (330 nl) with a 200 watt fianovia lamp for one hour. Yhe solvent was removed under vacuum to give a brovm liquid

(5.765 g). The brown liquid (1 g) was chromztographed on neutral aluninm oxide in chlorofom to give 1:-pheneth-1- acetamide (686 mg, 94%) whose i.r. sgectrw was s~peri~posable with that of an authentic sample. The amount of the -thermolysis product, henethylacetate, was very small as indiciied by a very weak i.r. absorption peak in the 1765 cm-l region. 5. N-nitroso-IT-cyclohexylacetarilide . The N-nitrosamide (1.05 g) was photolyzed in solution A (100 ml) for 33 hours with a 100 watt Hanovia lamp. One half of the photolysate was reacted with Brady's reagent as usuai

but no 2,4-dinitrophenylhydrazone precipitate was obtained. 6. IT-nitroso-N-11-butylf orixmide.

The Ti-nitrosamide (3.78 g) was photolyzed in solutLon A for 5 3/4 hours. The photolysate was distilled under atmos- pheric pressure to give 164 ml of distillate. Half of the distillzte was refluxed with i3radyts reagent for 3 hour to give 2,4-dinitrophenylhydrazone of n-but anal (76.3 mg, 3.0%) which was recrystallized from ethanol-water mixture, mop. and nixed mop. with the 2,4-dinitrophenylhydrazone of an authentic sample of n-butanal was 120-121QC. - - General pyocedur~of 2hotolyoes in 1:eutrxl ecia.

Photolyses were carried out i~ ca. 0.1-0.4 -.. solution under a nitrogen atmosphere with a 100 nat '; ;isnovia Gtility lamy, a General Electric PAR 38 spot lamp (100 watts) or in sualight. In the former two cases the solution in a 2yrex flask wzs cooled externally with 2 nater screen running zlong the exterior of the flask. The light c;as passed through the nc,:ter screen into the solution. In the latter case, the solution in a 13yrex flask was irmersed in a bath of mniiing aster and plzced in sunlight (by the window). The photolysis tenoerature was thus controlled in ail cases in the range of 10-20•‹C throughout the photolysis period. The 2hotolyses were continued until the typical uv absorption peaks of L-nitrosainides disappeared. Dark reactions were perfomed in nost cases a control and uv ebsorptions at 410 ap regions v!ere taken at the end of the photolysis period. The photolyses viere run in 4 solvent systems: (1) in n-pentane; (2) in benzene (3) in cyclohexane (4) in petr~leumether, b.p. 34-35OC. The yields of the 6-oximinoanide , starting axide, ester and other identified products were listed in Table 111. - - 1. i,-nitroso-X-n-hexylacetamide The X-nitrosamide (6.5 g) in n-pentane (100 ml) was -$iotolyzed in sunlight (with the exclusion of ovgeiI) ;or

11 days. The solvent was removed to give a mixture of crystals md oil (4.71 g). k portion (2.8 g) of the crude product sas used for recrystallizz~bionin acetone-pentane mixture to give the C-nitroso dimer XIX as flzke like clystals (755 mg), m.p.

Analysis calcd. for C15H32N404: C,55.82; ~~9.36;N916.27. Found: ~,55.07;K,9.35; --li,16.51.

Xolecular weight: determinetion in H20:

The filtrzte from the acetone-n-pentane recrystallization 'Jas dissolved. The aqueous solution was then extracted with ether. Zvaporation of ether from the ether fraction gave 511 ng of a liquid which was hydrolyzed in 1N HCl in 80:; ethmol- aater solution (50 nl) at room temperature for 20 hours. A yellow liquid (439 mg) was obtzined from the methylene chloride extract of the hydrolysate. This was chromatographed on neuJ~ralaluinina to give many smll fraction, none of which contained a sufficient amount of pure substance for identification. . . %'hen the water was removed from the aqueous fraction, a yellow liquid (646 mg) was obtained. This yellow liquid (645 mg) was chromatographed on neutral alumina with chlorofora to give the C-nitroso dimer XLX (303 me) described above. It was hydrolyzed in 10 ml of 1X XC1 for 20 hours at room 8.04.(s, 31I), E.1-e07(rn, 42); 8.33(t, 311,

\ J=7.2 c.P.s.).

ii dccoupling experiment ivsn done on thc liquid ;:XI viith a Varic:n 100 L:c n .nor. spec trophotomet cr. ',-hen the iriplet I at 7;2..99 waq irradiated, the q~crtetnt ~7.56collrpscd to P

~in,clet.:?hen the quartet c7t -~7.55:.m5 irradiated, the triplet ~t ~8.99collapsed to 2, singlet. Liquid XXI vaa trez.ted with Srady's rec~entto zive 30 mg of 2,4-dinitrophenylhydrazone which Y!E3 recrystallized from ~lcohol--:later to give yellow needles (2Z<11), mop. 9&96"~.

The crude photolyzate (974 mg) was chro~atogrrphedon neutral slumina, (i) Slution with 25.3 chlorofom in benzene Ccve a light yellon liquid XVIII (463 mg) . T3e i .re spec :rum of XVIiI had c moderzte shsorption peek ;t 873 cn-l, but othervise the spec-hum mas superixposa'~1ewith that of the prrent s:zide,

;t-oleculcr weight, determined by t::erxister dro~nethod, -.~.s found to be 172. 22 (ii) Xlution with chloroforn Cave the C-nitroso dirner XiX (376 mg, 27.7::). Xo n-hexylacetate was isoleted. Its presence *::as indicated only by the weak absorption peak of carbonyl and acetate groups at ca. 1720 and 1220 cx-' in the crude photolyzate. In a separate experiment, the photolyses of i;-nitroso- 2:-n-hexylacetamide (3.12 g) under nitrogen in sunlight for 5 days gave a deposit of solid in the photolyzate. The solvent was removed from .the photolyzate to give a mixture of brown liquid and crystals (2g), part of which (1.98 g) was chroaatographed on neutral alumina: (i) Blution with 25% chloroforn in benzene gave a liquid (512 me). 'The i.r. and n.m.r. spectra of this liquid were superimposable with those of the liquid XVIII from the pre- ceding experiment. (ii) Elution with chloroform gave crystals, mop. 125- 12T•‹C (791 mg). The i.r. and n.m.r. spectra of this crys- tzlline compound were superimposable with those of the C-nitroso diner 2~1~identified in the previous experiment. This C-nitroso diner XIX (750 mg) was hydrolyzed with 111 aqueous hydrochloric acid solution (30 ml) at room temperature for 48 hours and then heated on steam bath for additional 24 hours. The extraction of the hydrolysate with methylene chloride gave a yellow liquid (160 mg). Chromatography of the yellow liquid on iieutral almina with 255; chloroform in benzene gave the b -ke toa..xi.de AX1 (5G.g ;ng) . r:3330(s), 1707(s), 1650(s).

Treatinent of this ketone with r: calculated amount of 3radyfs rea~entgave 2 hydrzzone LXII which xas recrystallized from alcohol and ;vater to give yell-on needles, mop. 119-121•‹C. Analysis calcd. for Cl4;Il9W5O5: C,49.82; H,5 .@;B,20.76. Yound: C,49.89; H,5.85; X,20.81, 2. 4-Phenylbutyl-~S-~zitrozcetamide . The X-nitrosamide (4.7 g) in 'petrolem ether (100 nl) was photolyzed in diffused sunlight for 21 days in nitrogen ataosphere. 3hen the solvent mas removed from the photolyzate, a brown liquid was obtained (4.322 g). k part of the brown liquid (1.26 g) was hydrolyzed in met:ianolic .hydrochloric acid solution (16.35 ml of concentrated hydrochloric acid in 100 ml of methanol). The hydrolysis was continued for 25 hours. Sodium carbonate solution (10:;) was added to the hydrolyzate xtil the pH of the solution was ca. 9. The brown oil which apgeared in the alkaline solution mas extracted with ether. When the ether extract was evnporated, a brown liquid (477.7 mg) was obtained. Aqueous hydrochloric acid (6N) vizs zdded to the aqueous layer until the solution was neutrzl. The neutral solution was extracted with nethylene chloride. The

ethylene chloride extract gave a brown liquid (117 me) upon evap~~atiox.The i.r. of the liquid from the ether and the methylene chloride extrzcts were superinposable. i.: 3350(m), l724(w), 1630(s), ;98(~) 24 Attempts to przpre 2-phenylpyrrolidine from the brown liquid were unsuccessful. In a separab photolysis , 4-phenyl-n-butyl-2;-ni Iroso- acetaxide (5.03 g) in petroleum ether (100 ml) was irradizted with a 100 watt Hanovia lamp at 6-10•‹C in a nitrogen atmosphere for 31 hours. The photolyzate separated into two organic phzses. :Then the solvent was ~emovedfron the supernatznt liquid, a yellow liquid (1.42 c) was obtained which was characterized as 4-phenylbutylaceJ~ate,

i : 292O(s), l705(s), 1630(n), 1604(w), 1262(~), l244($), 1160(~),695(s). n.m.r.: 8.38(qu, J=3.8 cop., 415); 6.34(t, J=7.5 c.?.s. 2H); 2.77(s, 5H).

itYhen the solvent was renoved Irom the lower layer, 2 thick brotm liquid A (3.98 g) was obtained.. About 1/4 of the brown liquid was separated by column chromatography and ca. 1/2 mas hydrolyzed. The chromatography of the liquid A wzs performed on neutral alumina (Brockman Activity 1).

(i) dlution with chloroform-benzene (1:9 ) gave the parent amide (316.9 me;) as indicated by its i.r. spectrum which was superimposable with that of the authentic saxple. (ii)Slution with ethanol-chlorofom (1:50) gave the corresponding oxime (334.6 mg) which was recrjistallized from 95;; ethaiiol and petroleum ether to give white crystals, m.?. 112-113•‹C,

i.: 3360(m), 3240(n), 1618(s), 1572(s), 758h), 590(m). 25 n.n.r.: 8.25(qu, J=6.5 c.P.s., 28); 8.04(=1, 33); 7.l(t, J=7 c.p.s., 2H); 6.72(q, ~=6.5c.p.s.,

2~);2.28-2.45(m, 215); 2.55-2.53(m, 3i:). Analysis calcd. for C12H1602N2: C,65.42; Ii,7.32; X,12.72. Zound: C,65.45; :i,7.35; X,12.92. Liquid A (1.02 g) was subjected to hydrolysis for 24 hours by ref luxing ic ne thanolic hydrochloric acid solution (16.35 ml of concentrated hydrochloric acid ink100 nl nethanol). The hydrolyzate was evaporated to ca. 30 ml which was neutralized with 105; potassium carbonate solution. The neutral solution was extracted with ether. The ether extrzct was washed with a small amount of water and then dried with magnesium sulfate. The etheral extract was filtered and after evaporation of the ether a brom liquid was obtained (676 mg).

3be aqueous layer was extracted with methylene chloride. dvaporation of the methylene chloride extract gave a yellovl liquid (155.4 rag) which was chronatogrzphed on neutral alursina. (i)Blution with benzene gave a clear yellow liquid (100 mg) vhich was tentatively assigned structure XXIil on the basis of its i.r. and n.m.r. spectra. i:3500(~), l6l8(s), lMO(s), '/b~is),630(~) . n.m.r. : 2.2-2,7(m, 5H); 5.9(t, 2H, J=7.5 C.P.S. ); 7.12(t, 2X, J=9 c.P.s.); 7.97(q, 2K, J=7 c.p.s.)* This fraction was dissolved in 20 ml of tetrahydrofuran. Platinum oxide (7.2 mg) was added to the solution. The solution was then hydrogenated at room temperature under a pressure of 60 lbs. p.s.i. for 2 hours. The solution was filtered. Lvaporat- ion of the solvent from the filtrate gave a brown liquid residue which was chroiaatographed on silicic acid to give 5 sinall fractions. Jach fraction was treated with piccic acid but no picrate derivative of compoundXXV11 was,isolated. (ii) Elution with chloroform cave light yellow cryatals (332 mg) which were recrystallized from benzene-cyclohexane to

n.m.r.: 2.15-2.9(m); 6.59(q, J=7.0 c.p.s.); 6.94(t, J=7.0 c.p.s.); 8.0(m) Analysis calcd. for C12H15N02: C,70.22; H,7.37; N,6.82* Pound: C,69,61; E,7.19; n,7.53. The brown liquid A (1.21 g) was hydrolyzed a second tine in 250 ml of 13 hydrochloric acid methanolic solution for 38 hours with refluxing. The solvent was removed with a rotary evaporator until the volume was rednced to about 40 ml. The hydrolyzate was made basic (pi-; 9.5) and extracted with ether to give a yellow liquid (408 mg). The yelloa liquid was trested with lithium aluminum hydride (5.2 g) in reflux- iilg tetrahydrofurzn (80 ml) for 43 hours. athyl acetate (ca. 40 ml) was added to decompose the unreacted lithium aluxinum hydride. About 30 ml of 61: H SO was added to the solution 2 4 in an ice bath. Addition of concentrated sulfuric acid to the solution caused the forxation of z precipitate. The 27 solutior; was filtered and sodiu;i: hydroxide solution (165) was added to the filtrate until the pIi was about 13. 'The solution was then extracted with methylene chloride. ;'hen the nethyleiie chloride extract was evaporated, a brcnn liquid

(195 ng) was obtained. This brown liquid mas treated with f-toluenesulfonyl chloride (205 mg) with vigorous shaking in the presence of sodium hydroxide solution (10:;) :vhich r:as added to the reaction mixture until the pH was 10. ,This solution was left at room temperature overnight, after dhich time the reaction mixture was extracted with ether. Lva~orat- ion of the ether extract gave a brown liquid (357 rig). Chroxatography of the brown liquid on neutral alumina with benzene gave a yellow liquid which was further chro~atographed on silicic acid with chloroform to give the p-toluenesulfon- amide of 2-pnenyl-pyrrolidine. Final purification was effected by sublimation (120•‹/0.2 rim) to give gale yellow crystals follov~leaby recrystallization from methanol and petrolem ether to give needles, m.p. 103-105•‹C.

i:173O(s), 1600(s), 1343(s), 1154(~).

3 iq-aitroso-N-n-hexylf or;naixi.de . The B-nitrosofomamide (5.99 g) in n-pentane (100 nl) was photolyaed under ni-trogen for 10 days in sunlight. Phe photolyzate separated into two layers. A brown liquid (4.6 g) was obtained after the ~olventwas removed fro$ the the supernatant solvent J.ayer. The light yellon li (ju' r: pvc an i.r. sbso2ption peak at 1775 cn-l indicating the presencc of n-hesylforinz-be. The brown liquid from the lower layer (1.39 g) ?;!as chronatosraphed on alumina,

(i) ~lutionwith chloroform: benzene (1:l) save the parent Torlilamide (405 mg); the i.r. and il,m.y. spectra of which were superimposable with those of ail autiientic senple of n-hexylf orril&ide. (ii) Blution with ethanol:chloroL'orrn (1:20) gave 4- oxi:nino-11-hexylf ormarriid e (727 me) .

58(lOO:j). Analysis calcd. for C7EIl4X2O2: C,53.15; 9,S.92; Ry17.70. -- YOU~~:~$53.37; ~,8.82; ~~6.33. -- 4. -i\-~~itroso-i?-benZ~l~~et8~ide. The 9-nitrosamide (2.02 g) in cyclohexane (500 nl) nas 2hotolyzed under nitrogen i:? sunlight for 17 d~ys.?he solvent nes renoved fro9 the photolyzzte to give a 'orem liquid (2.22 - g), a portion of which (1.14 g) miis chromatog-cghed on 9ectrzl alumina. (i) Blution with chlorof orxi: benzene (1:3) gai-e the pa~ent 29 a:iide (734 g, 76.91;) which was identified by its i.r. and

11.m.r. spectrz. (ii) Slution wiLh ethanol:chloroform (l:g) gave white crystals of 1,l-diacetanidotol-uene (05 mg) , m. p. 238.5-240•‹C.

1a.s.: n/e 147(9.70,;), 132(7.44,*3), 104(16.015), 77(18.12~3), 59 (16.015), 43(100,'7). 3enzylacetate was not isolated nor was it detected in the i.~. spectruii of the crude photolyzate , - 3. 1;-nitroso-X-ohenethyl~icetamide . The B-nitroszni.de (5.05 g) was photolyzed in cyclohexane (200 nl) in sualight Tor 7 days. The photolyzate separated into two layers. The solvent was removed from the entire photolyzate to give a brown liquid (3.82 g) of which 2.00 g was chroma t ographed on neutral alumina. (i) Elution viith benzene and benzene :chloroform (1:3) gave the parent amide (1.544 g, 77 i) whose i.r. and n.m.r. spectra were superinposable with those of an authentic sanple of phenethylacetzmide. (ii)Zlutioil. with chloroforra gave 1,1-diacetazido.-2- phenylethane (45 mg, 2.5$), m.p. 213-217 C. ire 3300(rn), 1650(m) -- Analysis calcd. for C12H16b~202: C,65.43; H,7.32; ~,12.72 Found: C,63.94; B,7.33; s,11.44. 6a. --14-nitroso-17-nethylca7~oanide in n-pentane ,

The 2:-nitrosarnide (4.95 g) in n-pentane (300 ml) was photolyzed in su~lightfor 11 days in a nitrogen atnosghere. 30 When the solvei2t was reuuved from the photolyzate, a brown liquid (4.709 g) ws obtained of which 1.15 g wss chroxato- graphed on silicic acid. dlution with chlorofom gave a clear gellov liquid (540 ng, 46.8 ;). The i.r. and n.1a.r. spectra of this yellow liquid were identical with those of cn authentic sszple of il-::.e thylcaproamide . The presence of ,xthylcaproate nas in2icated by the 1-ieak aborption pesks at 1720 and 1210 cm-I in the i.r. spectrum of the crude product. The brovm liquid (2.02 g) from the photolyzate was chroxatoeraphed on neutral alu~inaand the f ollovri.;~ results were obtained.

(i) Blution with chloroform: benzene (1: 3) gave a clzar yellow liq-did (902 ng, 54.7 ;) whose i.r. and n.n.r. spectra were identical with those of en authentic saaple of >I- ethyl- caproaxi.de . (ii) Slution with chloror^orm:benzene (1:l) gave ccystals (86 ng) which were recrystallized from acetone-n-pentane mixture to give white c~ystals,mop. 175-177 OC.

i.r. : 3320(s), 1635 (s), 1553(m), 1537(d, 1418(d, 1380(n), 1134(m). The amount of pure white crystals was too small for ident- ication. (iii) 2lution with ethano1:chloroforr~ (9, 1:3, 1:l) and 956 ethanol gave a mixture of sticky yellow ccystals

(307 :i&) which were refluxed with Zit hydrochloric acid for 2 hours. The hydrolyzate was stean distilled. The residue was extracted with metnyiene ciilorida contiluoucly ior ;vith cthcr , nhich nken removed ,-,-eve a ycllow liqt~id(llC 1~1::) . .-Lile 7 liquid3 ob-Lrined fror.1 the ether 2nd rnethylene c::loriCe

cxtrzct were c?irolirzto~r~n~ed on c silicic c- cid colu~r,.i;o?.i- evey, the frc-ctions coll-cctcd were peen rnd ap~e:lrcc: to 11; ve c; ~ri~,-ed. 61,. :T-nitro 30-~~-~1eth:rlc:~i~r0~1:1idcin cgclolie;;r.nc~

A separ~te photolysis experiment ivz 3 run with the I:-nitro- c;ariide (4.8 8) in cjrclohexane and under nitro~einat:?os?here aith a 300 ws,tt tungsten lanp for 31 days. The sol-rent -:E-,

removed from the photolyzate'to give 2 brom liquid (5.76 g)

of vrhicii 4.56 g nccs hydrolyzed x: th 2S Ilydrochloric ccid for k 3 hours on a stcan bath, 17he hydrolyz~te7i183 extr~ctedcon-

tinuously ~5thchloroforx for 24 hours. &- hrowr! liq~-id(3.1G g) wa obtsined upon cvaporztion of the chloroforn extrzct. Chromatoyxiphy of the brown liquid (3.06 g olotc?.ined fron hydrolysis) on silicic acid gcve, with cblorofom, r ;~ellov~ liquid (1.01 g, 32;z). #The i,r. ~i~dn,m.r. s~ectraof this yell-om liqujd were superixposzble with those of' r n c?ut;lentic sample of IT-methylca proamide,

6c. T\;T-ni-l;roso-1'J-methylc,-,nror1~idein netr+ol earn e :;her. A tl-lird photolysis of this 2-nitrosay1i.de (5.38 g) in petroleum ether (30 zil) for 03 days undeY ni :ro -e? nt-,!osphcl:.e in sun light, Petroleun ether (100 ml) nc.3 r66es:. to t':c solution durin~tl?c pho-tolysis to :nri_ultain t::e s?mc 32 concentration. The solvent was removed from the photolyzate to give a brown liquid (5.65 g). ',"'hen the byonn liquid. was trezted with 2rady's reagent, gw-ny yellow solids were obtained which decomposed during recrystzllization fro3 ethanol-wzte:-. The brown liquid (1.47 g) was chromatographed on neutral alumina.

(i) Elution with ch1oroform:benzene (1:g) gave 2 yellow liquid (356.4 ng) which was further chromatographed on silicic acid to give, with 505 chloroform in benzene, 1;-nethyl- caproamide (224.2 mg, 19.2:;). (ii) 2lution with ch1orofora:benzene (1:l) gave czproamide (99.5 mg, 9.11%) which was mblimed (72"/0.2 mm) to give shite needles, m.p. 91-94OC, mixed m.p. with an authentic sanple of caproamide (mop. 96-97•‹C) 95-96•‹C. The i.r. and n.m.r. spectrz of these needles were also identical with those of an authentic sanple . -- * 7s. a-nitroso-I<-methyltoluemide in petroleum ether. The N-nitrosamide (5.75 g) it petroleum ether (150 ml) .:as irradiated with a 100 watt Iknovia lamp for 141 hours under nitrogen atmosphere. The solvent was removed from the

photolyzate to give stic-y yellow solids (5.59 g). These

solids were chromatographed on a neutral alumina ~01~11~. ,:uch dilficulties were encounted in separsting the rolids because they could not be dissolves completely in chlhroform and benzene. The solids (999.5 mg) were therefore dissolved in 33 a warm sc71ution o< 30 x1 ethanol 2nd 5 ml chloroTorm. iifter this solution was introduced to the nei~tralaluxina (zctivity

3) colurm, white solids soon formed iil the sea sand as beczene was introduced as the eluent. dthanol (10 ml) nes a.;ded in an attexpt to dissolve the caked solids, but they did not dissolve

completely. A crystalline compound (396 mg, 38:;) wac eluted with benzene. It was recrystallized Prom acetone-petrolem ether and identified as compo~md XXXI, m.p. 134-137OC.

i:3360(s), 3250(w), 1624(s), 1595(w), 766(s) n.m.r.: (acetone) -0.6(broad); 1.33(s); 2.0-2.6(m); 7.02(s); 7.l(d, J=5 c.p.s.) Analysis calcd. for C9H10N202: C,60.66; H,5.66; X,15.72 Zound: C,60.55; H,5.54; N,15.73. The recovery of products from the aluinina chromatography was 46.8,;. 3enzene (100 ml) was added to the sticky solids (910 ng)

sild warmed to give a viscous ye$low lower layer (711 ng) and a supernatant benzene layer. b7hen 50;; chlorofomn-ethanol (10 ml) solution was added to the lower layer, a milky solution was obtained which was centrif'uged to give a white powdery preci2itate (130 ng) . This precipitate was recrystallized Sron ethanol to give needles (63 mg). The needles turned sof5 snd no m.p. was taken. The centrifugate decomposed to dark liquid when it was eva2orated. The i.r. spectrm indicated that the soft crystals contained a nitrile group.

i.: 325O(tv), 2500(w), 2220(~),1648(s), 754(s). 34- -- A s::cond eAiperii;Lenton the ?hntolysis of the L-L~~TOSO- - - ,i-;;,e t:;yltolua;.,icle (5.42 C) in pc troleun ether ($00 nl) w2s

perToraeci uder nilropn etmosphere with a 100 wz:t General

dlectTic PA2 38 spot la~1.3 Tor $7 hourc. ?he nhotolyzate gave

3 stic:iy yellow solid (j.09 g). (This solid (1.02 g) as hydrolyzed :or 39 hours in nethanolic hydrochloric acid solution (16.35 ml of concen -rzted hydrochloric acid in 1CO nl of ,.;ethanol). -.I,.,nen the solvent was removed from the hydroiyzate to reduce the volurie to about 20 ml, needles zppzeTed in the solution. The solution was filtered. 'he aeedles gave a i.spectrum v!hicil was superimgoszble with that of phthaliaide prepared according to Herzog's methos (16). The needles were recrystallized fro:^ ethanol-'uater solvent, n.p. 197-19g•‹C. i.: 3270(n), 1775(n), 1610(m), 716(s). Analysis calcd. for C8H5MC2: C,65.42;. 3,3.42. Zound: C,64.78; Ii,3.61. The acidic filtrate (ca. 4/5) was extracted continuously for 24 hours with methylene chloride. :','hen the solvent was removed from the methylene chloride extract, a yellow liquid

(705 3g) was obtained. Xo product was obtained from the chroaztography of the yellow liquid.

.'he re;lzining l/j of the ~cidicfiltrate was neutrclized

r:ith 10,; aqueous sodiun czrboilate and then extracted with ether. -.iothing - was obtained aftel the removal of ether from the ether extract. A part of the sticky crude product (364 mg) nas adied to 35 15 nl of ethanol and dissolved upon warming. Addition of a calculated amount of drady's reagent gave 299 me of 2,4- dinitrophenylhydri?zone LAX11 which was recrystallized from ethyi acetate, i2.p. 280-250.5•‹C. i.r.: 3400(w), 1800(m), 1746(s), 1624(s), 1600(m), l55O(w), 385(s), 835(s), 738(m), 700(s). n.m.r.: (dimethyl sulfoxide, see fig 1) -0.3 '(s, 1E); 1.03(d, 1H); 1.98(~,4H); 1.7-2.42(~,U system, 211). Analysis calcd. for C281!18i;8G11: C,52.34; H,2.84; 5,17.44. Found: C,52.04; Ii,2.75; 1:,16.77. 7b. i;-aitroso-iu'-raethyltoluamide in benzene. In a third experiment, the photolysis of 1;-nitrosanide

(5.43 g) sas performed in benzene (400 ml) with a 100 wait General Glectric PAR 38 spot lamp under nitrogen atnosphere. The photolyzste consis-Led of a brown precipitate and a yellow supernatant liquid. The solution iias filtered to give brown

crystals A (2.91 g). A brown liquid B (2.61 g) was obtained

from the filtrate after the renoval of the solvent. A part of liquid B (1.93 g) was chromatographed on neutral elmina to give the follov~ingfractions. (i) The second benzene fraction (400 ml) gave K-nethyl- toluzmide (373.7 nig, 31.~~~) (ii) The first benzene frnction (500 ml) gave a thick liquid (235.5 mg) ~hichwas further chromatographed on silicic acid to give the follovling fractions. a. Elution with chloroform initially gave methyl 0-toluate 36 (40.8 ixg, 0.12 ;). i..: 1720(s), 1600(w), 1030(m), 734(m). n.n.r.: 7.42(s); 6.16(s); 2.1-2.8(m).

b. Further elution with chloroform gave white needles W:llch were purified by sublimation at 5g0/0.2 rm, m.p. 57-61'~. The i,r. and n.m.r. spectra of these indicated that the needles could be phthalide. i.r. 1740(s), 1620(w), 1600(~),1050(s), 1000(s), 739(s). n.n.r.: 4.68(s, 23); 2.0-2.G(m, 4-52); small impurity at 6(s) and 6.83(s).

(iii)Continued elution with chloroform gave finzlly the parent arlide (35.6 mg, 1.08%).

The crystals "AY(1.02 g) from the yhotolyzate were recrystallized from acetone and petroleum ether to give neeales (390.2 ~g,20.435), mop. 132-135'C. The i,r. and n.m.r. spectra of these needles were superiniposable with those of the oxime :(XCI. The filtrate from the acetone-petroleum ether recrystallization were evaporated to give a yellow liquid (600 mg) which was civozatographed on silicic acid to give tke following frzctions.

(i) Zlution with chloroform initially gave EW as a ng, vfhite c-qstalline compound (22.5 1.4.;) which- was purified by sublimation st 40•‹/0.2 m.p. 129-131'~ (lit. 132-133'~)

(19) i.r.: 1756(w), 1720(s), lGlo(~),714(~) n.s.: m/e 161(100r~),132(11%),104(52.2$$), 76(50.1$). 37 (ii) Continued elution wi$h cliloroform gave st ran-coloured needles (153.6 rng, 9.25';) ::hich were recrys'iallized from ethanol azd vt2te-r to give white needles, u.p. 218-221•‹C. The i.r. specJ~rmof these needles was superimposzble with

(iii)Llution with ethanol in chioroform (2',:) gave crystals of IXjCIII nild ZUI7 (150 mg) , m.p. 202-205'. 'TLe crystals appeared to be ~ronzticnitriles as indiczted by the i.r. ebsorption peaks at 2240 and 1959 crn-l. Xowever, further re~~ystellizationfrom ethanol gave a single crystalline comgound (2.5 mg) with no absorption at 2240 cn-l. The aother liquor was therefore chronatographed on silicic acid but no nitrile compound was obtained. Instezd, this chromatography with chloroform gave crystals (55.4 mg) whose i.r. spectm nas identiczl with that of XYJVI. The brown liquid 3 (1.93 g) was chromatographed on neutral almnina with benzene to give a thick liquid (238 mg) which was further chromztographed on silicic acid with chloroform to give a light yellow c~ystsllinecompound (64.4 ng, 2.25:). This conpowd vias sublimed at 7g0/0.2 m to give white crystals XXX , m.p. 57-61•‹C, whose i.r. spectrum mas superinposable with that of an authentic sample of phthalide. i.r.: 1750(s), 1616(~),1282(n), 1206jrn), 730(s). n.m.r.: 2.04-2.45(m, 4-5H); 4.69(s, 23). The crystals "8" (1.18 g) dissolved in 20 ml eti~anol- the hydrolgzaie mas renoved, white needles were obtained. The i.r. spectrum of these needles was superimposable with that of compound XXXI. Comgomd .CZI (150 mg) was dissolved in 10 ml of 955 ethanol. Xitrogen was bubble6 through the solution for 15 minutes and then it was photolyzed with a 100 watt General ilectric PA2 38 spot lamp for 24 hours in running water bath at 12OC. Yt'hite needles were obtained after the removal of solvent lrom the photolyzate. The white needles appeared to be z nixture of compound XXXI and ni-lriles. i.: 334O(s), 32OO(s), Z23O(w), 1640(s). 8. Control Experiments. Control experiments weze performed in the dark under the sane reaction conditions for each H-nitrosamide. The uv spectra viere taken at intervals during the experiment periods. There nas little (less tiisn 5;) or no change in the uv absorbance I of the nitroso peaks tnrouzhout the entire period of the I control experiment. 39 . iil WSULTS. lhotolyses In Acidic, 1,:edi.s. The 27-nit roso-N-zlkylace tznides and f ormamides were pre- payad according to ',!hiteta method (17). The amide was nitrosated with nitrous acid. The yellow B-nitrosamide thus obtained was used without purification except in the preparation of Z- nitroso-W-n-butylacetamide which was distilled at room teaper- ature under vacuum. The photolysis temperature was controlled rigidly at 10-20bC in order to ninimize the thermal decomposition of the N-nitrosamide. Desgite this careful control, a small amount of ester, the product of themolysis, was observed in a few experi~entsas indicated by the weak absorption 2eak at ca. 1730 cm-l in the crude product of photolysis. The rate of photolysis ranged from 0.005 mole 2er liter per hour to 0.077 mole per liter per hour, depending oil the type of lamp used. Sowever, when comparable lamp and solvent were -- used, the time required for the photolysis of the A-niCroso- S-Senzylace t 2mide was much longer than that for the X-nitroso- 1;-phenetjlylacetarnide. The xajor ;products of photolysis kvere the parent amides and the hydrolysis products which could be derived from alkylideniinides . 'Ihe 2,4-dinitrophenylhydrazones of the aldehydes which forned upon hydrolysis of the latter aere prepared for identification. The yield of the 2,4-dinitrophenylhydrazones of the aldehydes

2nd :he parent amides varied over a wide range. The yield 40 of the respective 2,4-dinitro~henylhydr2~011esderived Proin the photolyzates of the N-nitroso-ii-3-butylace bazide, --.,-nitroso-

R-a-hexylace t a.rni.de and :T-nitro so-1;-n-butylfo-nnarnide ranzed from fcir (35:;) to poor (3:;) (see Table 11). 'i'hile the photolyzates of the IT-i~it~oso-Ti-phcnethyl and :he -,:-nitroso- - K-cyclohexyl-acetaaiides did not yield any corresponding 2,4-dinitr~phenylhyd~azo~ieat all, the photolyzate of the

K-nitroso-X-benzylacetaanide in both solvents A and 3 gave . excellent yields of the 2,4-dinitrophenylhydrazone of benzaldehyde (775 and 38;s respectively). Repeated chrornatoeraphy of the crude products f ron the photolysis of 1i-nitroso-N- benzylacetamide in solvent 3 gave a crystalline compound which was identified to be 1,l-diacetanidotoluene XVII.

Chart VII. Photolgsis of N-nitroso-IT-benzyl~cetamide.

Despite careful attempts to purify compound 3311 by recrystallization, only reasonable analytical results were obtained. This is apparently due to decomposition during reccystallization. The mass spectrum of compound XVII suggested the likelihood of a facile thermal decomposition as the molecular ion peak of comyound XVII was absent in the spectrum. The highest mass peak was m/e 147, equivalent to ::-acetyl benzylideninine. ;;evertheless, tLe i.r. and n.m.r. spectra of compound XVII characterized the structural 41 assig:.~r.lent. 'Tlie i.r. absorption peaks at 700, 750, 1660 2nd 3270 c::;-l indicated the preseiice of nono-substituted benzene ring and an amide group. In the n.m.r., spectrw, the si~nals at ~2.56,t6.2 and t8.03 iil the ratic of 5: ca.1 : 6H were assigned respectively to be aromatic protons, methine and methyl protons.

Photolysea in Neutral Mediz. The preparation oP 19-nitroso-13-4-phenyl-n-butylacetamide, in spite of careful work-up, gave a mixture consisting of themal decomposition product, the 4-phenyl-n-butylacetate, as indicated by the i.r. and n.m.r. spectra. Separation of the N-nitroso-IT-4-phenyl-n-butylacetemide from the ester by vacuum distillation at room temperature was not possible, because of the thermal instability of the if-nitrosoacetamide. This mixture was then used as the starting material in the

photolysis. i The photolysis was performed in a nitrogen atmosphere using a lamp or diffused sunlight as the light source. The temperature was controlled in the range of 10-20•‹C. The characteristic yellow colour of the N-nitrosamide solution faded as the photolysis proceded. the photolysis was completed, the photolyzate separated into a clear, colourless supernatant and an oily or crystalline lower lzyer. The major products of the photolysis were the parent anides and t5e rearranged products as shown in Table 111. The major rearrangement product was the 5-oximinoanide. The yields of parent amides and the S-oxininoamides varied, depending very nuch on the nature of the allcyl and acyl groups attached to the anide nitrogen (-3 an6 -Rt groups in compound I). Thus, while the yields of the b-oximinoanides from the - - pLotolysec ,of the J,-nitroso-X-4-phenyl-n-butylaceta ..ide , M-nitroso-N-toluylacetanide and N-nitroso-11-n-hexylforaamide varied from 50-30~;, the photolyses of 7;:-nitroso-Z-benzyl- ac2tamide and B-nitroso-N-phenethylacetamide gave no 6-oximinoamide . Parthermore, the photolysis of N-nitroso-X-n-herjl- acetaxide yielded no corresponding 6-oximinoamide but the 2-nitroso dimer XIX instead. The fornation of the dimer XIX was subs'tantiated by a cryoscopic molecular weight determination in water. It was shown to be a trans-C.-ni-troso diner by its i.r. absorption peak at 1178 crn-l &ich is typical of a trans diner (18). The multiplet at t4.65 (one proton) in the n.m.r. spectrum 6 was assignable to the methine proton. The C-nitroso diner XIX was hydrolyzed ultimately to the corresponding ketone ;

Chart V The Photolysis of ~T-nitroso-l~-n-hexy1acetamide in ;:eutral Xedia and the Hydrolysis of C-ni-troso Dimer.

0 I I Compound TI111 CH3 ( CS, ) 4C~2-g-C-CH3 (Not Identified) 0 d II ) 3ilHCCH3

11? HC1; . 0 4 ll OH CH3CH2CH(CH2 ) 3i!dHCCHs i (XIXI CX CH C ICI12 ) 3NHjCH3 211 Brads's Reagent + 0 0 11 0 (XXI) i'I 3 (IXXII)

1:02

compound possessing i.r. absorption peaks at 3380 and 3240 cm-'. 3ile the triplet at ~7.11was cssigned to the ,:ethylene

-.LTroup nest to the oxime group, the two superimposed tripleto equivalent to two protons at t6.73 could be as-igned to the me thylene group next to the amide nitrosen atom. "L'e de~ener- ation of the latter triplet can be explained by the restricted rotztion 02 the carbon-nitrogen bond. The restricted rotation of the carbon-ni$rogen bond was probably due to the delocalization of the non-bonded electrons of the nitrogen atom in the amide grou? (13). The n.m.r. spectrum, therefore , clearly supported the structural as~ignnentof XXIZI. ':,'hen the oxime XXIII was hydrolyzed to the corresponding ketone XXV, the i.r. spectrum now showed a new absorption peak at 1670 cm-I vlhich was assignable as the carbonyl group conjugated with the benzene ring, The n.m.r. spectrw slioned a triplet at t 6.79 which was assigned to the sethyl- ene group next to the anide group. It also showed a triplet at t7.05 miiicii was zs:;igned to the methylene group next to the benzoyl group. Despite many attempts to purify ;LXY by recrystallization from acetone and cyclohexane, a good aicroanalysis was not obtained, apparently this was due to contamination by compound XXIII. The correctness of this assignment wxs further demonstrated by the reaction of co,.lpound ZIII in the following manner. The crude product fro;,; the photolysis was redi~cedwith lithium aluxinum hydride. Treat~e~tof the reduced naterial with sulfuric acid followed by Eiiisberg' s reaction Lave compound :XVIII which xas 45 characterized b-i the m.c.. The m/e 301 peak (Xt) indicrLed the enpii1icel formula or" compo~nd~,i~~i;to be Cl7Kl9iIl~J1O2* The fornation of a 9yrrolidine ring in con7ound AXVII?roved that the nitroso sroug had indeed rearranged to the $-carbon aton Cram the anide nitro~en.

Chart IIX.

The photolysis reaction was next applied to 11-nitroso-N- n-hexylforrnanide to deternine if there would be any change in the photochemical pathway, if the acetyl group was replaced 4 G by a f orql group. The corresponding 5 -o;tii-ainofor :z.niOe

:i;iX..

-the xiethyl and tile oxin:e groups. The m.s. of this S-oximino- formani.de :KXSIIIb exhibited a weak molecular ion peak

(n/e 153) and stronger peaks at m/e 156, 141 and 130. 2he m/e 155 was formed probably by the loss of two hydrozen atoms to forrn the corresponding 6 -oxininoisocyanate . The n/e 10 peak was formed probably by the loss of the hydroxyl group. The n/e 58 peak could be due to CH2=C-143-OH as illustrated in + Chart X.

Chart X.

The Cleavase of the 6-oxirnino-n-hexylf-.-.- orazmide .+ upon ~lectronImpact.

- - The time required for the photolysis of: X-nitroso-;.;- n-hexylformamide mas about the same as that for the corresponding ecetamide. However, in the former ceoe, no dimer of C-nitroso compound sirniln to XIX nas isolated. Tne course of the photolyses of ;J-nitros~:T-be~~:/l~~~tarr,ide and N-nitroso-N-phenylacetainide were quite diiTerent from those described above. These two X-nitrosoacetanides have no alkyl group at the $-position from the arnide nitrogen atom. Thus, only the parent anides , i .e ., G-benzylecetanide end ti-phenethylacetanide , were recovered from the respective ghotolyses. The yields of amide were good in both cases.

Chart XI. The Photolysis of N-nitroso-N-phenethylacetamide in Feut ral I.ledia . 0 0 II hb II 0CH CH HCCH3 > SCH2CH2h'HCCX3 2l n-pentane

In the photoche:~ical experiments in neutral media dis- cussed so far, the compounds studied had hydrogen attached to the $-carbon of the chain attached to the nitrogen atom in the amide group. It was also of interest to study the photochemical behaviour of iq-nitrosamides where the hydrogens on the $-carbon were on the acyl side of the amide group. X-nitroso-X-methylcaproanide and S-nitroso-il-methyltolualide were therefore photolyzed. In the photolysis of X-nitroso-3-methylcaproamide in 48 petroleuin ether, the ratc of ~liotolysiswas slow. In contrast to the photolysis of X-nitroso-N-n-hexylacetamide, the photolysis of ;;-izitroso-1;-caproamide gave neither oxime nor C-nitroso dimer. l,'Jhile the liquid crude product decomposed during the silicic acid chromatography, the neutral alwnina chronatography of the crude product separated into xzny small fractions from which the starting amide and caproanide were identified. Yhe latter was identified by mixed melting point determination znd coinparison of its i.r, and n.m,r. spectra with those of an authentic sample of caproamide.

Chart XII.

The Photolysis of Ti-nitroso-N-methylcaproamide .

0 0 11 h v II CH3 (CH ) CijCii3 - CH3 (CH2) 4CH=CH2 + [S!JO] 24~ I

CH3 (CH ) CNH2 + HCX 411 I1

F'hotolysis of the N-nitroso-N-ze thyltoluamide gave sticky solids which were separated by neutral alumina chromatography to give the crystalline oxime, xX;~I. The i.r. absorption pealisat 3370, 3260, 1638 2nd 1598 cm-l supported this assigned structure. When the sticky crude products were treated with 3rady1s reagent, a high melting 2,4-dinitrophenylhydrazone,XXXII, was obtained. This dimeric liydrazone 49 - .. :dXI ~12salso obtained when oxine ;'C;

Figure I

n .iii.r. Spectrm of Compound %=I1 in Dimethyl -Sulf oxide.

On hydrolyzing the crude product in a mthanolic hydrochloric acid solution, some high melting needles were obtained. These needles were a mixture which'gave an i.r. spectrul~ having absorption peaks at 3270, 1775, 1750 and 1610 crn -1 which indica$ed that the mixture might contain 9hthalic anhydride and an amide. In spite of much effort, a pure coiiipound could not be isolated Prom the nixture. A third photolysis of the N-nitroso-1:-nethyltoluanide was carried out in benzene. The chromatographic separation of the crude product gave compounds XXXVI and XGCV. The i.r. zbsor2tion peaks of compound IL-rn at 1756, 1720, 1516 and 714 cs-l indicated the presence of an o-substituted benzene ring and sn hide group. The m.s. of XXXV su5stantiated the structural assignment as N-methyl phthalimide . The m/e 161 50 peak indicated the empirics.1 formula of the compound to be CgH7RO2. The m/e peaks 132, 104 and 76 suggested the losses of the groups -KCH3 , -CONCH and -C 0 BTCH respectively. mhe 3 2 2' 3 melting po.int at 129-131•‹C of the ccmpound X'CVI (lit. 132- 133'C) (19) furthemore proved its identity. The high melting crystals XXXVT were identified to be phthalimide. Compound XXXVT gave an i.r. spectrum which was superimposable with that of an authentic sample of phthalimide. The m/e (I$+) peak in the mass spectrum suggested the empirical formula C8H5J02. Besides the lY+ peak at 147, the m/e at 104 and 76 peaks could be due to the losses of the -CONH and the -C202NH groups respectively. The first two fractions from the alumina chromatography of the crude photolyzate were further separated by silicic acid chromatography to give whi te crystals which were identified as XXX. The i.r. spectrum of these crystals was superimposnble wi.th that of an'authentic sample of phthalide. Much difficulty was encountered in the microanalysjs of the compounds which gave absorption peaks at 3150, 2240, 1690, 1580 and 760 cm-l. These absorption peaks suggested the presence of nitrile, carboxyl and amide groups in the compounds. These nitrile compounds are suggested to have the structures of XXXTII and XXXIV. The mass spectrum of these

\ comounds indicated that these two compounds were present as a mixture. Furthemore these compounds decomposed during recrystallization. 2nd 102 peaks v:ere probably due to the 10s:; of -Ci13, -hilCii 3 due -Lo tile loss of both ni-Lri3.e and N-riietl~yl-a::lidyl poups . The m/e 147 peak is equivalent to CeI1211C2 nirich is the f ri-,lula of c0;;1po~md iXXIV. Tt did not zppear to be nrro'o~ble that the m/e 14'7 peak could result from tile cleavage of cornpound XXXIII. The m/e 130 peak could also 'ue due to the loss of a hydroxy group from compouild .L,XiV. The loss 02 both the carboxy!.. and .the nitrile groups froill coinpou-nd 2';IIV would give the m/e 75 peek.

Chart XI11 \ yh? Photolysis of ~-nitroso-3~-tolu-ylacetarnidein Keu :re1 ;:e(?i?. pi . Benzene or petroleum ether (2::)

\ IV DISCUSSIOIIT. --3liotolyses of X-nitrosaxldez in !icidic Kedia. The control exijeriments perforued in the dark indiczte

that thz decori~positionsof id-nitrosanides% - observed in acidic nedia are a true photoreaction. The ch,?racteristic uv absorption peaks at 395, 408 2nd 427 nr regions of the li-nitrosazides

persist throl~ghouttho entire photolysis 2ericd i,-1 the con- Lroi experiments. ';!hen the B-nitrosei':i:l.de solut~onis irradiated, these uv absorption peaks and the characteristic yellow colour of the solution fade as the photolyses proceed. At this stage, it is not known if a free radical mechz;2isn is npplicable tothe photolyses of N-nitrosamides. However, in the photolyses of the N-nitrosanines in acidic media (5)

(leas than 0.3 in hydrochloric acid), a free radical nechan- ism is reported to be unlikely inzsxuch as the photolyses are not altered by the presence of. oxygen (21). '?he nitrsso goup in 3-nitrosamine has been repor-bed to form hydrogen bonded 1:l complexes with an ~cidin cyclohexane (22). The Tirst complexing site with methyl carbonium ion has been shown to be at the nitroso oxygen atom (23). There is a possibility that the 1;-nitrosamide in acetic acid so1ut;on formed a comglex which nay undergo a [?;OH] elimination in a xanner analogous to that of 1;-nitrosamine photolysis (5). The elinination of [i:~iI] Trom iq-nitrosar~ide I sill lead to the formation of the alkylidenimide 1;XXVII which is not isolated because of its facile hyLrolgsis under the re-ction conditions to give carbony1 coxgounb and acetanide. ;his hy~otheticalneciinnisi3 of tile photolysis 01 Il-nitrosa ides is su>ported by the experi iental da 5a of the photolysis of 11-nitroso-E-n-buty1a~eta;;~Ide in acetic acid soSution. -;:hen the photolyzate of the 11-nitroso-ii-n-butylace'iaaide is treated wlth Brady's reagent, 2,4-dinitrophenylhydrazone of n-butanal is obtsined. The experinental results of the photolyses of N-nitroso-I:-benzylacetamide in aqueous acetic acid and in methasolic trifluoric acetic acid solutions

furthzrmore sup2ort the hypothesis that [1:CRl is eliminated froi~the X-nitrosamide upon irradiation. The yield of 2,4- dinitroghenylhydrazone of benzaldehyde from the photolyzate of L-nitroso-3-benzylacetemide is excellent -(776) in the for;.ler solvent and good (33%) in the latter. Therefore, the experiments support the propose1 that the photolyiic nechanisn * of IT-nitrosaxides in acidic media is similar to Yt~zzt'of

1%-nitrosanine (11) but different from that of the Barton - reaction. Cbart XIV Xechsnism of the Pliotolgsis of 3-nitroszmides -in Acidic iiedia. 54 It i.; not !mown why the yicld 01 t'tc 2,4-dinl troi:qcr:* - - :;SET:-r.0r.e from the nhotolyzrte of :-nitr~~o-~:-n-bu~t;~I~:cetcptidc is 5ct Ler thn tliai: fron tke pliotolyz~kc of :-nitro:o-"- n-huty1for.-,aniide, nor is it undcrs tood why t:ic 7ho tolyr

the ::-nitroso group)of the ;rnide nitrancn rtoin to the 6-carhon. , For excmple, it is proven by the i.r. ~nd1i.m.r. zpectra 2nd the dccoupling exnerimcut thzt the nitroso Sroup of t:)c C-nitroso- dimer, XIX, is att~chedto the S-carbon from the anide nitrogen atom. This nitroso-hydrogen exc::angre probably involves a r~di.~elmechanism. This i?y;~othesisis b~sedon the fo1lo:;l- ing ohservetions. Zira-c of all, the initiation of the rerctzon requires a ohoton. This is proven by the ahsencc or 2-e~ction in the control ex-)erinents in the derk. ~~~~~~~~~~~e, the pllesence of oxygen reduces the yield of the rearrzngeri~ent product :.;XLII. :'or instznce, the photolysis of A-nitroso- X-n-hexylaceiainide in n-pentane in the ebsence of oxygen yields 41.2;; of the C-nitroso diner XIX, wheras in the presence of oxygen, the yield decreases to 27.7%.

Chart XV General Photocher,:ical l..e chailisin of ::-nit rosaxide.-

A possible pathway of this nitroso-hydrogen exchznge leading to the fornation of the 5-oxi~inoarnide is proposed as shoxn in Chart XY. The photoexcited N-nitrosemide cen undergo homolytic cleevage to give anide and nitrogen oxide radiczls. The anide radical can abstract a hydrogen nton intermelecularly from the solvent, foming the parent anide, 56 or intranolecularly i'rora a 6-carbon through a 6-membered

Icransitioil skate to give a 6-carbofi radical (fron XLX XXl

urated and unsubstituted precursors. This photochexical zesction carried out in a single flask and in a single stes is an exanple of free-radical synthesis that would be difficult or even impossible to accomplish by a non-radical approach. In general, the parent snide and the b-oxininoamide (or the corresponding C-nitroso compound) are the nsjor poducts. There were several side reactions occurring d~lring -- the photolyses. .:hen the acetaxide group was re-121zced by a - - r^or.:xmi.de group es in the czse of the F-nitroso-..-n-hexyl- forxai:iide, the yield of he photolysis aroduct S-oxiaino- fornaaide decreases to 23:;. The cause of the decrease in the 57 yield of the 6-oxininoani.de is probably the formation of isocyanate as shown in Chart XJI. This side reaction probably

Chart XVI.

Possible Side.- :{ezc-tion of the Photolysis.- of N-nitrosof ormmide .

occurs to a small extent but the corresponding isocyanate ig not identified. No rearrangement product is identified frox the photolysis of B-nitroso-N-nethylcaproanide. The elimination of [XOH] Is one of the alternative procesEes leading to the formation of XXIX which can in turn be hydrolyzed to give the observed by-product, n-caproamide. The B-nitrosamide v;ith no available 6-alkyl hydrogen atom such as iq-nitroso-X-benzylacetamide and B-nitroso-II- phenethylacetamide, give only the parent amides upon ph~tolysi~. They are probably forned by intermolecular hydrogen exchange. The photolysis of K-nitroso-N-4-phenyl-n-butylacetamide in petroleum ether yields the $-oximinomide XXXIII. The hydrolysis of 5-oxirninoamide XXXIII followed by lithiuii aluinin-om hydride reduct ion gave 6 -hydroxglanine XU1 (not isolated) which cyclised to form 2-phenylpyrrolidine, XLVII. Although the yield of the pyrrolidine is smzll, this re~ction may Se a useful route for converti~lganides or mines into pyrrdlidines. It further emphasizes the increasing useful- 58 ness of nitrogen radiczls in organic synthesis. Beside c tile oxime XXXI, phthzlide , phthalimide and 2,-nethylphthaliziide were also detected as the !moducli,s of

At,-ie I photolyses of 'I\:-nitroso-IT-methylt~lua~~ide.X mixture of nitriles XXXIII and XXXIV was also identified. 2hese tvo conpounds are conceivably Tornea by dehydration of the oxime

AAXI,,P-- 7 since Iurther photolysis of the oxime 2XI or chromato- ~raphyof .,Xi1 on a silicic acid column does give the nitriles. Compouild XILYIV is Imovm to give phthalinide on heating in solution (29). It is conceivable that cosipound XZIII will lead to the fomation of M-methylphthalimide in the saxe uanner. It is obvious that the nitriles are interr'lediztes leading to the fomation of phthzlimide, and X-methylphthzl- imide . The f or:nat ion of nitriles f roiil the oximinoa.nide ZXI in acidic solution is understandable, but it is not understood how irradiation with uv light can aid the forxiation. Cue to thermal decoaposition caused by the heat radlated I~onthe lamp or sunlight, a small amount of carbinyl ester was observed in certain cases. In most cases, its presence is detected only in the i.r. spectra of the crude photolyzzte. The above studies point to an exclusive nitrogen-nitrogen bond cleavage of photoexcited nitrosamides as the primary ghotoprocess. This nitrogen-fiitrogen bond cleevage is striking- ly aifferent from the nitrogen-carbonyl bond (I-III) v:hich occurs in the tliermally excited i:-nitrossrnides. The latter thermolysis rezction h~sbeen thoroughly studied by varicus group (24+28). in conclusion it is now ob-~iousthat the ~hotolytic patiixay of X-nit rosaxides in neutral nediz difi'erz frox thzt in ccidic rnedia an6 tLat they ;:re botl: light irzduced reaction. oxininoamide XU1 upon elution through a silicic ecid

colmm. These nitrile COX~OU~~~Swere also obtained xhen the 6-oxioinoarnide XXXI ivas irradiaked with -the 100 mtt General Electric PAR 33 spot lanp in a neutral solution. These results indicatc that the well known 2eckmnn rearrange-

:i~eili;of oxixes to ni-trilerj may ta!ce place under photolytic these conditions lias not been investigated. ~Jurtiierstu.c'y of the photolye5 s of onnes io surely warrented as it n:-y provide a method of converting oxirnes to nitriles in the presence of acid sensitive groups and may lead to furkner interesting reactions 01 oxines. G1

Tcble 11.

The Products of i~liotolysesifi Acidic ;..ed.ia. 5 Yield of 2,4- - - ;\;-nitroso- Solvent Di\!PI-i* of Carbonyl ,: Yield of Ct,!er zce.i;t:.xides Systems Comnound s Parent ;.=ides Products

1,l-diacet- amidotoluene

N-phen- B ethyl i<-cyclo- A hexyl

- - ::-nitrosoformamides Tlie--- Products of Photolyses in ;:eutral .,..edia. -

X-nitroso- -oximino- Parent ace'caniaes amides Anides Esters -Other 2roducts Identified W-n-hexyl n-liexyl- (CH ca caca CH ca i~acca~)~ acetate (f) 321 22211 (In ) - - :T . 1. 0

N-n-hexyl (In air) n-hexyl- (CX CH CBCE2CH2CH2@HCCH3)2 - - acetate(#) 3 21-- 1I 8 I

-- ?I, -4-phenyl- n-butyl 47.576 52.5% -

1;-nitroso- -0ximino- Parent f orxaai.de amide Amide Ester- Other Products Identified

N-n-hexyl 28.0$ 26.5% n-hexyl- forinate (f) Table III (contfd).

Other 3-oducts Ir!entified

19.2% methyl- n-ca proamide ,9.1% caproate (#) t G luarnide 15.2$ methyl- phtnalide, 18 i; toluzte, phthalimide , 2.5 :; 0.12% it-methyl phthalimide;

(f): Zster was not isolated. Its presence was indicated by the i.r. spectrun only. n -3- LO m i-i A V 4- LO Ln (3 L.0 i-i CU w

n S.L. Shriner, R.C. Puson and D.Y. Curtis, S:~stec- atic Identification -of Cr; anic Co:.;po;~nds,5th Ld., John ',.'iley & Sons Inc. , Xew York, ii.Y. , l96$.

W. Herzog, 2. agnew Chem. 32, I, 301 (1919); Chemical

3.H. White, -J. ,&I. -Chem. SS., -77, 6008 (1955). Xunio notoke, Constants of Organic Compoulrds, Baakura Publishing Co., Ltd., Tokyo, Japan, 1963, p.426. D.J. Cram and G.S. iiamnond, Organic Chemistry, XcCran- Eill dook Co., Inc., New York, ii.Y., 1959, p. 173. Dictionzrx -of Organic Conpounds, Vol. 5, 4th Xd., Eyre & Spottiswood Publishers Ltd, London, 1965. G. Sosnovsky, Free Radical Reactions -in Frepzrztive Orgznic Chemistry, The XacXillan Co ., New York, 2 .Ye ,

1T.S. Layiie, E.H. Jaffe and H.. Zimer, ---J. Am. Chela. %. , ---88, 435 (1963). A. Schmidtpeter, Tetrzhedron Letters, 1421 (1963).

J.2. Buchholz and R.Z. Powell, -J. -Am. -Chem. -*)Soc -985

-4. Streitweiser and U.D. Schaeffer, ibid 79, 2893 (1957). -9 - B.E. Bachmann and R.A. Hoffman, 0rg;znic Resctions, Vol. 11, John Wiley and Sons Ina., Xew York, N.Y., 1944,

D.B. Denny, B.G. Gershnzn and A. Appelbaun, --J. An. Chem. 28. 2.L. Eliel and J.G. SaXa, ibid, 3581 (1965).

29. Dictionary & 0ry;m.i~Compounds, Vol. 2, 4th 3d., iyre L Spottiswood Publishers Ltd., London, 1965, p. 754.