Reactions of tert-Butylperoxy Esters, XIII Reactions of

Reactions of tert -Butylperoxy Esters, XIII Reactions of Dialkyl ferf -Butylperoxy Phosphates with A m inesa,b,c G. So sno vsk y,

E. H.

Za r e t ,

and A.

G a s ie c k i®

D epartm ent o f C hem istry, U n iv ersity o f W isconsin-M ilwaukee, M ilwaukee, W isconsin 53201, U S A (Z. Naturforsch. 30b, 724-731 [1975]; received February 17, 1975)

ferf-B utylperoxy E sters, D ialk yl C ycloalkylam m onium Phosphates, ferf-B utylperoxy P h osp h ates, D ia lk y l P hosphates, A m ines The interaction o f dialkyl tert-butylperoxy phosphates, ( R 0 ) 2P (0 )0 0 C M e 3 (1) with prim ary and secondary cycloalkylam ines, R 'R " N H , R ' = cyclo-CeH ^, R " = H ; R '= R " = cyclo-C 6H n (2) in th e presence and absence o f w ater, produces th e corre sponding dialk yl cycloalkyl am m onium phosphates, ( R 0 ) 2P ( 0 ) 0 - N +H 2R " R / (3), and ferf-butanol. In carbon tetrachloride th e reaction produces in addition to 3 th e corre sponding cyclohexylam m onium chloride, P ossible m echanism s o f th e reaction are discussed.

Introduction The reaction of organophosphorus compounds with hydrogen peroxide in the presence of amines to produce colored products is known as the S c h o n e m an n reaction and it forms the basis of a sensitive method for the determination of phosphoruscontaining nerve gases1-3. The reactions of isopropyl methylphosphono-fluoridate ( S a r in )4-6 and diethyl p-nitrophenyl phosphate1-3-7 with hydrogen per oxide in aqueous alkaline solution in the absence of amines involve rapid nucleophilic attack by the hydroperoxy anion on the phosphorus ester. The peroxyacid then slowly undergoes either a bimolea T his paper is dedicated to Professor Dr. E u g e n M ü l l e r in honor o f his 70th birthday. b This investigation w as supported b y grants from th e U . S. D epartm ent o f H ealth , E ducation, and W elfare, P ublic H ealth Service (GM 16741), and from th e Graduate School o f th e U n iversity o f W isconsinM ilwauke. c Prelim inary results were com m unicated in G. S o s n o v s k y and E . H . Z a r e t , Chem. Ind. 1967, 1297. d P resent address, The H artz M ountain Corp., H arri son, N ew Jersey. e P resent address, G. D . S e a r l e and Co., In c ., Skokie, Illinois. R equests for reprints should be sent to Professor Dr. G. S o s n o v s k y , The U n iv ersity o f W isconsin-M il w aukee, D epartm ent o f C hem istry, M ilw aukee, W is consin 53201, U SA .

cular reaction4 or a unimolecular decomposition followed by rapid formation of oxygen6. To date, no esters of monoperoxy phosphoric acid are known, and a recent attempt to synthesize them was unsuccessful8. I t is, therefore, not possible to study their reactions with amines. However, in the presence of acetone or other carbonyl compounds the interaction of aromatic amines with inorganic peroxyphosphoric acid has been reported9to produce phenolic derivatives of the amines. Although organophosphate esters are found in all living systems many organophosphorus compounds are extremely toxic and have been used as in secticides and war gases. The toxicity of such compounds, e.g. S a r in , is ascribed to their ability to inhibit, through phosphorylation of histidine or serine or both, cholinesterase-type enzymes. Diisopropyl £er£-butylperoxy phosphate (1, R = i-C 3H 7) was shown in our laboratory10 to be a mild cholinesterase inhibitor in rats. Therefore, it was of interest to investigate the interaction of peroxyesters (1) with imidazole and histidine. Such a study is complicated by the extreme instability of dialkyl phosphorylated imidazole11 and histidine derivatives. Thus, the reactions of peroxyesters (1) with cyclo-alkyl amines were chosen as model systems.

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G. SOSNOVSKY E T A L . • REACTIONS OF DIALKYL *er*-BUTYLPEROXY PHOSPHATES Results

The reaction of peroxyesters (1) ( R = C 2H 5, i-C3H 7) with cyclohexyl- (2, R '= cyclo-C6H 11; R " = H ) and dicyclohexylamine (2, R '= R " = cyclo-C6H u ) yields, both in the presence and absence of water, the corresponding amine salt of the cognate phosphoric acid (3) and tert-butanol as the major products (Table I). (R 0)2P(0)00C M e3 + R R 'N H -> 1 2 (R 0)2P(0)0-N +H 2R 'R " + Me3COH 3 R

= C2H 5, i-C3H 7, R ' = eyclo-CßHn,

R " = H, eyclo-C6H u . The reaction of peroxyesters (1) ( R = C 2H 5, with piperidine, phenethylamine, diphenylamine, aniline, and triethylamine failed to produce isolatable crystalline salts. However, the IR spectrum of each of the reaction m ixtures evidenced the band at approxim ately 2200 cm-1 characteristic of ammonium salts. The reaction of peroxyester (1) (R = i-C3H 7) with benzylamine a t 40 °C did not proceed and the peroxyester and amine were recovered by distillation. i -C3H 7, w-C4H 9)

In addition to the m ajor products the reactions

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produce intractable colored oils. In the case of the interaction of peroxyester (1) (R = i-C 3H 7) with cyclohexylamine in benzene, traces of cyclohexanone oxime, diisopropyl N-cyclohexylphosphoramidate (4, R = i - C 3H 7; R ' = cyclo-C6H n ) and at least two unknown components have been elucidated by tic analysis of the residual colored oil. In addition to the fer£-butanol, the volatile products have been shown by glc to contain traces of acetone and methanol. In order to obtain some clues on the mechanism of the reaction of peroxyesters (1) and amines (2), the reaction was carried out in carbon tetrachloride. The reaction of amines with carbon tetrachloride has been shown12-13 to produce the corresponding amine hydrochlorides among other products. The reaction seems to involve ionic, charge transfer, and radical species, and therefore, one could assume th a t this solvent might have an influence on our reaction. However, the results shown in Table I indicate th at no substantial change of product composition has occurred. Thus, the reaction of equimolar amounts of diisopropyl tertbutylperoxy phosphate (1, R = i- C 3H 7) and cyclo hexylamine in carbon tetrachloride solution at 25 °C produces a 26% yield of cyclohexylammonium chloride and a 26% yield of diisopropyl cyclohexyl ammonium phosphate (3, R = i- C 3H 7; R '= c y c lo C6H l i ; R " = H ) .

T able I. R eaction o f dialkyl tferf-butylperoxy phosphates (1) w ith am ines (2) (R O )2 P (0 )0 0 C M e 3 + R 'R " N H (R O )2 ( 0 ) 0 - +N H 2R 'R " + tert-B uO U . 1 2 3 R

Peroxyester m ol

; - c 3h 7 c 2h 5 *-c3h 7 ; - c 3h 7 i-C3H 7 *-c3h 7 ; - c 3h 7* *-C ,H 7* ; - c 3h 7 *-c3h 7 *-C3H 7e ; - c 3h 7 «-C3H 7b ; - c 3h 7 c 2h 5 c 2h 5

0.02 0.05 0.04 0.02 0.05 0.02 0.02 0.025 0.025 0.025 0.039 0.02 0.02 0.02 0.02 0.02

R' cyclo-CBHj cyclo-CgHj cyclo-CfjH! eyclo-C sH j cyclo-CgHi cyclo-CgH! cyclo-CeHj cyclo-CgHj cyclo-CßHj cyclo-CgHj cyclo-CgHj cyclo-CgHj cyclo-CgHj cyclo-CgH i cyclo-CßH! cyclo-CgH!

R 'R " N H R" H H H H H H H H H H H H H H cyclo-C #H xl cyclo-C 6H u

m ol

Solvent [ml]

0.02 0.10 0.05 0.02 0.1 0.04 0.04 0.05 0.05 0.05 0.039 0.02 0.02 0.04 0.048 0.02

none c 6h 6 c 6h 6 c 6h 6 c 6h 6 c 6h 6 c 6h 6 CC14 CC14 CC14 CC14 c h 3o h c h 3o h C2H 5OH c 6h 6 c 6h 6

(25) (15) (25) (50) (25) (25) (50) (50) (50) (25) (25) (25) (25) (2 0 ) (10)

Tim e [h]

Tem p [°C]

Salt 3 R ^ 'N + H g C lY ield [%] Y ield [%]

12 16 14 504 5 18 1 168 168 2 20 9 17.5 18 39 48

25 25 25 25 70 40 40 25 25 25 25 25 40 40 25 25

55 53 54 84 79 68a 55c 57 30 21 26f 32 32 56 54 59

Trace 30 16 26

a Y ield o f salt 3 lowered b y rem oval for titra tio n o f five 0 .5 -ml aliquots o f th e reaction m ixture before th e salt w as isolated. b R eaction carried out in the presence o f 0.002 m ol galvin oxyl (9). c Y ield o f salt 3 lowered by rem oval for titration o f three 0.5-m l aliquots before the salt w as isolated. d R eaction carried out in th e pre sence o f 0.05 mol w ater. e R eaction carried o u t in a g loveb ox filled w ith dry nitrogen. f In addition, 46 percent peroxyester w as recovered. 8 R eaction carried out in th e presence o f 0.01 mol sodium m ethoxide.


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G. SOSNOVSKY E T A L. • REACTIONS OF DIALKYL «ert-BUTYLPEROXY PHOSPHATES

The mechanism by which peroxyesters (1) react with amines to produce the corresponding dialkyl N-alkylammonium phosphates remains unclear. Nucleophilic attack on phosphorus by the amine can be expected to yield the corresponding dialkyl N-alkylphosphoramidate (4) and tert-butyl hydro peroxide. (R 0 )2P (0)00C M e3 + R 'N H 2 -> 1 (R 0 )2P (0)N H R ' + Me3COOH 4 Reaction of £er£-butyl hydroperoxide with the amine might then yield the corresponding imine and £er£-butanol14.

(a) A proton transfer [R'N+H20C(CH3)3][(R 0 )2P (0 )0 -] -> 5 (R 0)2P (0 )0 H + R /NHOC(CH3)3 6 7 (R 0)2P (0 )0 H + R'NHOC(CH3)3 ->• 6 7 R 'N H 2 + [CH3OC+(CH3)2] I (R 0)2P (0 )0 (R 0)2P (0)0-N + H 3R ' + CH2=C(OCH3)CH3 3 8 (b) A cleavage to give radicals

Me3COOH + R "CHNH2 -> R "C = N H + Me3COH + H 20 R " = (-C H 2- ) 5 Our results indicate that, although £er£-butanol is a major product, the reaction of peroxyester (1) (R = i-C 3H 7) with cyclohexylamine produces only traces of diisopropyl N-cyclohexylphosphoramidate (4, R = i-C3H 7; R ' ^cyclo-CgHn) and cyclohexanone oxime. Although phosphoramidates (4) are difficult to crystallize they are readily purified by sublimation as was shown using a synthetic mixture of a dialkyl cyclohexylammonium phosphate and the corre sponding dialkyl N-cyclohexylphosphoramidate. Moreover, if 1 is interacted with cyclohexylamine in the presence of phosphoramidate (4) the reaction proceeds normally to yield salt 3, and 4 is recovered without difficulty. These observations, coupled with tic evidence, lead us to believe th a t if phosphor am idates (4) had been formed in more than trace amounts we would have been able to isolate them. There is evidence th a t nitrogen compounds will participate in nucleophilic displacements on oxygen even though the picture is often clouded by data which could be just as readily explained on the basis of a free radical interaction15. Nucleophilic attack by the amine on the peroxide linkage can be envisioned as follows. (R 0)2P (0 )0 ö-0 R "C = N + H 2 + (CH3)3COH

R ' N H 2+

R "C = N + H 2 + (R 0)2P (0 )0 R //C = N H + (R 0)2P (0 )0 H Y

R //C = 0 + N H 3 R ' = Cyclohexyl; R " = (-CH2- ) 5 An alternative mechanism (c) involving nucleo philic attack on the peroxide in a concerted manner can also be envisioned. (c) A nucleophilic displacement

(q \

/C (C H 3) 3

(RO)2 p (R 0 )2P(O)OOC(CH3) 3 + r 'n h 2 — ► o -.h; nh

1 R'NHOC(CH3) 3 + (R 0 )2 P (0)0H

7

6

(R 0 )2P ( 0 ) 0 'N +H3 R' + CH2=C(OCH3)CH3

3

8

Our results do not permit a choice to be made between these or any other theoretically possible routes. On the basis of the product analysis, none of the routes shown is satisfactory since each involves some intermediates which were not intercepted. However, the reactions always produce


G. SOSNOVSKY E T A L . ■REACTIONS OF DIALKYL fert-BUTYLPEROXY PHOSPHATES

intractable tars and, therefore, product analysis is not a sufficient criterion for determ ination of the mechanism. Routes (a) and (c) are intriguing in th a t they explain the production of salt 3 without involv ing water. However, failure to isolate either m ethyl isopropenyl ether (8) or the O -tert-bu tyl hydroxylamine derivative (7) is disappointing. Methyl iso propenyl ether (8) is a product of the therm al decomposition of peroxyesters10 and although it is very reactive under the present reaction conditions probably would have been detected. O-ferf-Butyl N-cyclohexyl hydroxylamine (7, R ' =cyclo-C 6H n ) has not been reported. However, an analogous compound, 0,N-di4er£-butyl hydroxylamine (7, R ' = (CH3)3C), has been prepared and isolated either as the hydro bromide or hydrochloride and has been shown to survive treatm ent with aqueous acid solution16. Under the relatively mild reaction conditions employed in our experiments, it m ight be expected th a t 7 (R' ^cyclo-C gH ^) would have survived. The m ajor fault with the sequences is th a t they do not explain the production of £er£-butanol as a prim ary reaction product. A mechanistic explanation of the products of the reactions of peroxyesters (1) with amines is made even more difficult by the following observations. (1) The reaction of peroxyester (1, R = C 2H 5) in benzene in the presence of cyclohexylamine is much faster than is the disappearance of the peroxyester in benzene alone and the rate appears to be depend ent on the amine concentration. The amine thus appears to be inducing the decomposition of the peroxyester. (2) The reaction of peroxyesters (1) with cyclo hexylamine is faster in ethanol th an in benzene. This could imply an ionic interm ediate in the rate determining step. (3) The reaction of peroxyesters (1) with cyclo hexylamine is accelerated by the addition of galvinoxyl [2,6-di-£er£-butyl-a-(3,5-di-£er£-butyl-4oxo-2,5-cyclohexadien-l-ylidene)] (9), a free radical trap which usually retards free radical reactions. (4) The reaction of peroxyesters (1) with cyclo hexylamine is accelerated by the addition of 2,6-di-£erf-butyl phenol, a compound which usually retards free radical reactions. (5) The reaction of peroxyesters (1) with cyclo hexylamine is inhibited by the addition of azobisisobutyronitrile which usually serves as an initiator of free radical reactions. The inhibition, in this case,

727

can be explained by a reaction sequence involving the oxidation of the amine by peroxyesters to a nitroxyl radical followed by the formation of an adduct arising from the combination of the nitroxyl with radicals derived from the azobisisobutyronitrile17. oOxidation by 1 I CNC(CH3)2 R N H 2 ----------------------► R 'N H --------------- >► 0-C (C H 3)2CN I R 'N I H Observations 1,2, and 4 point to an ionic reaction as the rate determining step. If the rate determining step is indeed ionic, then the acceleration of the amine-peroxyester interaction by galvinoxyl points to the formation of free radicals at some point in the process. This conclusion is based (a) upon the production of phenol (10) and aldehyde (11) from the interaction of galvinoxyl with tert-butoxy radicals18, (b) upon the previously discussed inter action of inorganic peroxyphosphates with aromatic amines in the presence of carbonyl compounds9, and (c) upon our observation th at 2,6-di-£er£-butyl phenol accelerates the amine-peroxyester inter action. (CH3)3C ^ = ^

.C(CH3)3 (CH3)3C

3

(c h -j^ c ^ ^

c(CH ) 3 (cH3) 3

^ c c c h ^ (CH3)3C

Cch3)3c hoY oV cho (ch 3)3c^ 11

The results of this investigation, therefore, are not ameniable to interpretation by either simple ionic or free radical mechanisms. Experimental

Boiling points and melting points are uncorrected. IR spectra were obtained on a Perkin-Elmer model 137 spectrophotometer. Elemental analyses were performed by Micro-Tech Laboratories, Skokie, Illinois, or on an F& M Carbon Hydrogen Nitrogen Analyzer, model 185. Gas chromato


728

G. SOSNOVSKY E T A L . • REACTIONS OF DIALKYL ZerJ-BUTYLPEROXY PHOSPHATES

graphic analyses were performed on Yarian Aero graph instrum ents models 1700 and A-90P3 equipped with therm al conductivity detectors using wx filaments on a 10 ft x 1/8 in steel column packed with 100-200 mesh Porapak Q. Unless otherwise noted, materials were concentrated at less than 50 °C on a rotating evaporator at 10-15 mm Hg. Dialkyl phosphoric acids were prepared by the m ethod of Z w i e r z a k 19 and we have previously reported methods for the preparation of cüalkyl tertbutylperoxy phosphates20-21. Cyclohexylamine and the other amines were distilled over zinc under nitrogen and were stored over sodium hydroxide under nitrogen. Carbon tetrachloride was stored over calcium chloride. All other materials were the best commercial grade. W ith the exceptions of the solvents and inorganic reagents, all materials were purified by suitable techniques of distillation, re crystallization, sublimation, or chromatography before use. Unless otherwise noted, the petroleum ether used had b.p. 20-40 °C. P reparation of dialkyl am m onium phosphates (3 ). General procedure (Table I I )

Equimolar amounts of the dialkyl phosphoric acid (6) and the amine were stirred at ambient tem perature in the solvent indicated. The reaction mixture was concentrated on a rotating evaporator and the residual oils were crystallized and re crystallized as indicated. Determ ination of active oxygen content of peroxyesters The peroxide content of solutions of dialkyl tert-

butylperoxy phosphates was determined in analogy with the method of S i l b e r t and S w e r n 22. Thus, 15 ml glacial acetic acid containing 0.1% ferric chloride hexahydrate was purged with dry nitrogen for 5 min and 2 ml of a saturated aqueous solution

of sodium iodide was added. The sample was added and the flask was stoppered and stored a t ambient tem perature for 5 min. W ater (50 ml) was added followed by 5 ml of a stable starch solution (Fisher Chemicals, Inc.). The solution was titrated to a colorless end point w ith 0.1 N sodium thiosulfate solution. The procedure typically required a titra tion blank of 0.5 ml sodium thiosulfate. T hin layer chromatography

Peroxyphosphates and tert- butyl hydroperoxide were visualized by spraying the dried developed plate with a solution of sodium iodide in nitrogensaturated glacial acetic acid. They appeared as brown spots on a white background. All phosphorus esters could be visualized by spraying the dried developed plates with concentrated hydrochloric acid followed by exposure to iodine vapor and appeared as brown spots on a white background. This procedure is capable of detecting 5 /ug of phosphorus compound in a spot. The phosphoramidates were visualized by exposing the dried developed plates to iodine vapor, and they appeared as brown spots on a white background. Reaction of diethyl tert-butylperoxy phosphate ( i , R = C 2H 5) with cyclohexylamine Diethyl tert- butylperoxy phosphate (11.31 g,

0.05 mol) was added in one portion to a solution of 9.92 g (0.10 mol) cyclohexylamine and 25 ml ben zene and the resulting mixture was stored at room tem perature for 16 h. Filtration of the precipitate which had formed yielded a hydroscopic solid, m.p. 78-80 °C. Repeated recrystallization of the solid from benzene yielded 7.2 g (53%) diethyl cyclohexylammonium phosphate monohydrate. A n a lysis: Calcd for C10H 24NO4P • H 20 : C 46.50 ; H 9.65. Found: C 46.44; H 9.55.

Table II . D ialk yl cycloalkylam m onium phosphates (3) prepared from dialk yl phosphates (6 ). D ialk yl phosph ate (6 ) R

A m ine 2 R ' = C6H n R"

ch3 i -Pr n-Pr n-B u i-B u Me Et i-P r n-P r n-B u i-B u i-B u

H H H H H c 6h u C eH ,, c 6h u CeHjj C6H n C Ä , -CMe3

Solvent

CHC13 c 6h 6 c 6h 6 CHCI3 c 6h 6 CHC13 CHCIa c 6h 6 c 6h 6 CC14 c 6h 6 c 6h 6

tim e [h]

R eaction m .p. [°C]

1 1 6 1 1 24 24 19 3 60 3 1

* C, H , N an alyses were w ith in 0.3% o f th e theoretical values.


7 7 .5 -78 .5 198-199 8 1 .5 -8 3 8 1 -8 2 2 0 0 -2 0 1 .5 159.5-160.5 133.5-134.5 172-173 133-134 106-107 165.0-165.5 181.0-181.5

S alt 3* R ecry s. solven t

E th er-P en tan c A cetone Ligroin or E ther E ther P en tan e Ligroin -A cetone A cetone Ligroin A cetone A cetone Ligroin A cetone B enzene

G. SOSNOVSKY E T A L . • REACTIONS OF DIALKYL tert-BUTYLPEROXY PHOSPHATES Reaction of diisopropyl tert-butylperoxy phosphate (1, R = i-C zH y) with cyclohexylamine in the absence of solvent

Cyclohexylamine (1.98 g, 0.02 mol) was added in one portion without cooling to 5.08 g (0.02 mol) diisopropyl tert-butylperoxy phosphate. The re sulting mixture was stirred at room tem perature for 12 h during which time it slowly solidified. Repeated re crystallization of the resulting brown solid from acetone yielded 3.1 g (55%) diisopropyl cyclohexylammonium phosphate: m .p. 192-196 °C. Reaction of diisopropyl tert-butylperoxy phosphate ( l , R = i -CzH t) with cyclohexylamine in benzene solution

I. A t a m b ie n t t e m p e r a t u r e A. A solution of 10.2 g of (0.04 mol) diisopropyl tert-butylperoxy phosphate, 5 g (0.05 mol) cyclo hexylamine, and 15 ml benzene was stirred at ambient tem perature for 14 h. The m ixture was concentrated. Crystallization of the residual oil from acetone yielded 6.0 g (54%) diisopropyl cyclohexylammonium phosphate. B. A solution of 5.08 g (0.02 mol) diisopropyl tert-butylperoxy phosphate, 1.98 g (0.02 mol) cyclo hexylamine, and 25 ml benzene was stirred at room tem perature for 3 weeks and was then concentrated to an orange oil. Crystallization of this oil under 20-40 °C petroleum ether yielded 4.7 g (84%) of a tan solid. Recrystallization of this solid produced I.5 g diisopropyl cyclohexylammonium phosphate: m.p. 184-187 °C; and an uncrystallizable oil whose IR spectrum was essentially superimposible with the IR spectrum of pure diisopropyl cyclohexyl ammonium phosphate. II. A t 70 °C A. Into a 100 ml, 3-necked, round bottom flask equipped with thermometer, reflux condenser, drying tube, a — 78 °C trap, magnetic stirrer, and gas buret filled with saturated sodium chloride solution, and the entire system purged with nitrogen gas, was added a solution of 12.7 g (0.05 mol) diiso propyl tert-butylperoxy phosphate and 25 ml ben zene. To this solution was added a solution of 9.9 g (0.10 mol) cyclohexylamine in 25 ml benzene and the reaction flask was immersed in a 70 °C oil bath. When therm al equilibrium had been achieved (15 min) the flow of nitrogen gas was stopped and the gas buret opened. Gas evolution occurred for the first hour and 59 ml (5.3%) of unidentified gas was collected. The mixture was heated a t 70 °C for 4 h more and was then kept overnight at room tem perature. Concentration by distillation of the ben zene at atmospheric pressure under nitrogen gave a black residue. Crystallization of the residue from acetone yielded 11 g (79%) diisopropyl cyclohexyl ammonium phosphate, m .p. 194-196 °C; and 7.4 g of a black uncrystallizable oil which was analyzed by tic on alumina using benzene, ether, and ethyl

729

acetate as eluants and was found to be comprised of at least five components of which diisopropyl Ncyclohexylphosphoramidate, cyclohexanone oxime, and diisopropyl cyclohexylammonium phosphate were identified by comparison with authentic sam ples. The tic investigation eliminated the possibility of the oil containing cyclohexylamine or cyclo hexanone. The benzene distillate was shown by glc to contain tert-butanol (41%) with traces of methanol, water and acetone. B. A solution of 5.08 g (0.02 mol) diisopropyl tert-butylperoxy phosphate in 15 ml benzene was purged at room tem perature with nitrogen. A solution of 3.96 g (0.04 mol) cyclohexylamine in 10 ml benzene was added in one portion and the reaction flask was immersed in a 40 °C oil bath. The reaction mixture was then concentrated. Repeated recrystallization of the residue from acetone yielded 3.8 g (68%) diisopropyl cyclohexylammonium phos phate. Aliquots (0.05 ml) of the reaction mixture were periodically titrated for peroxide content. Elapsed time [h]: Percent peroxide:

0 100

1 96

3 96

6 78

10. 54.

A duplicate experiment was performed sim ultane ously; however, the amine solution also contained 0.84 g (0.002 mol) galvinoxyl. Analogous work-up after 1 h yielded 3.1 g (55%) diisopropyl cyclohexyl ammonium phosphate. Titration of the reaction mixture after 1 h was not possible because the mixture had almost solidified. Reaction of diisopropyl tert-butylperoxy phosphate (1, R = i -C3H 7) with cyclohexylamine in carbon tetrachloride

A. In the presence of water A m ixture of 6.35 g (0.025 mol) diisopropyl tertbutylperoxy phosphate, 4.95 g (0.05 mol) cyclo hexylamine, 0.9 ml water, and 50 ml carbon te tra chloride was stirred at room tem perature for 7 days. The reaction mixture was filtered to remove a small amount of cyclohexylammonium chloride. Recrystallization of the filtrate from ligroin yielded in several crops, 4 g (57%) diisopropyl cyclohexyl ammonium phosphate: m .p. 191-193 °C. B. In the absence of water 1. A solution of 4.95 g (0.05 mol) cyclohexyl amine, 6.35 g (0.025 mol) diisopropyl tert- butylperoxy phosphate, and 50 ml carbon tetrachloride was stirred a t ambient tem perature for 7 days. The solution was filtered to remove 2 g (30%) cyclo hexylammonium chloride. The filtrate was concen trated. Crystallization of the residue from acetone yielded 2.1 g (30%) diisopropyl cyclohexylammo nium phosphate. 2. Cyclohexylamine (4.95 g, 0.05 mol) was added over 9 min a t 22-25 °C to a solution of 6.35 g (0.025 mol) diisopropyl tert-butylperoxy phosphate and 50 ml carbon tetrachloride. The resulting


730

G. SOSNOVSKY E T A L . • REACTIONS OF DIALKYL «er*-BUTYLPEROXY PHOSPHATES

mixture was stirred at 25 °C for 2 h and was filtered to remove 1.1 g (16%) cyclohexylamine hydro chloride. The filtrate was concentrated. Crystalliza tion of the residue from acetone yielded 1.5 g (21%) diisopropyl cyclohexylammonium phosphate: m.p. 186 °C. 3. A glove box was purged with dried (H2S 0 4) nitrogen and a t intervals during the reaction the chamber’s drying-train was activated. The carbon tetrachloride (reagent grade) was dried over calcium chloride. The diisopropyl tert-butylperoxy phosphate was doubly distilled and was stored at — 10 °C but was warmed to ambient tem perature and opened in the glove box. A solution of 10.08 g (0.0394 mol) peroxyester in 25 ml carbon tetrachloride was dried over sodium sulfate and was decanted into the reaction flask. Carbon tetrachloride (25 ml) was added and then 3.9 g (0.0394 mol) cyclohexylamine (dried over sodium hydroxide pellets) was added in one portion. The reaction mixture was stirred at am bient tem perature in the glove box for 20 h and was then removed from the glove box. Cyclohexyl ammonium chloride, 1.5 g (28%), was removed by filtration and the filtrate was concentrated. Crystallization of the residual oil from acetone yielded 2.9 g (26%) diisopropyl cyclohexylammo nium phosphate. Distillation of the residual oil yielded 4.7 g (46%) diisopropyl tert-butylperoxy phosphate and an intractable black tar. Reaction of diisopropyl tert-butylperoxy phosphate (1, R = i-C 3H 7) with cyclohexylamine in methanol

A solution of 1.98 g (0.02 mol) cyclohexylamine, 5.01 g (0.02 mol) diisopropyl tert-butylperoxy phos phate, and 25 ml methanol was stirred at ambient tem perature for 9 h and was then concentrated to a yellow solid. Recrystallization of the solid from acetone yielded 1.8 g (32%) diisopropyl cyclohexyl ammonium phosphate, m .p. 195-196 °C. Reaction of diisopropyl tert-butylperoxy phosphate ( 1 , R = i-C 3H 7) with cyclohexylamine in the presence of sodium methoxide A mixture of 0.54 g (0.01 mol) sodium methoxide,

1.98 g (0.02 mol) cyclohexylamine, 5.01 g (0.02 mol) diisopropyl tert-butylperoxy phosphate, and 25 ml m ethanol was stirred a t 40 °C for 17.5 h and was concentrated to a yellow oil. Repeated recrystalliza tion from acetone gave 1.8 g (32%) diisopropyl cyclohexylammonium phosphate, m .p. 194-196 °C; and 1.9 g of an intractable brown oil, n ^ 1.4300. Reaction of diisopropyl tert-butylperoxy phosphate (1, R — i-C 3H 7) with cyclohexylamine in ethanol

To a solution of 5.08 g (0.02 mol) diisopropyl tertbutylperoxy phosphate in 15 ml absolute ethanol which had been purged with dry nitrogen was added in one portion a solution of 3.96 g (0.04 mol) cyclo hexylamine in 10 ml absolute ethanol. The reaction mixture was immediately immersed in a preheated

40 °C oil bath and 0.5 ml aliquots were periodically removed for titration of the peroxide content. Elapsed tim e [h]: 0 3 7 17. Percent peroxide: 100 98 20 0. After 17 h the reaction mixture was concentrated. Repeated re crystallization of the residue from acetone yielded 3.1 g (56%) cyclohexylammonium phosphate, m .p. 186-192 °C. An identical experiment was carried out in which the reaction residue was sublimated in an un successful effort to isolate diisopropyl N-cyclohexylphosphoramidate had it been formed. Reaction of diethyl tert-butylperoxy phosphate (1, R — C 2H 5) with dicyclohexylamine in benzene

A. Diethyl tert-butylperoxy phosphate (4.52 g, 0.02 mol) was added to 3.62 g (0.02 mol) dicyclo hexylamine. The mixture was diluted with 10 ml benzene and was stirred in a stoppered flask for 2 days a t ambient tem perature. The m ixture was filtered to remove 0.2 g dicyclohexylammonium chloride. The filtrate was concentrated leaving a dark brown solid. Recrystallization of the solid from skellysolve B yielded 4.0 g (59%) diethyl dicyclohexylammonium phosphate, m. p. 138-139 °C, which was identified by comparison with an authen tic sample by tic on silica gel G plates using acetoneethanol (1:1) and benzene-ethyl acetate (4:1) solu tions as eluants and iodine to visualize the spots. B. A solution of 6.50 g (0.029 mol) diethyl tertbutylperoxy phosphate, 10.5 g (0.048 mol) dicyclo hexylamine, and 20 ml benzene was stored at room tem perature for 39 h and was concentrated to a thick oil. Crystallization of the oil from petroleum ether yielded 5.27 g (54%) diethyl dicyclohexyl ammonium phosphate, m. p. 131-133 °C, a portion of which was recrystallized from cyclohexane yielding white crystals, m.p. 140-140.5 °C. A n alysis: Calcd for C16H 34N 0 4P : C 57.29; H 10.22; N 4.18. F o u n d : C 57.47; H 10.41; N 4.32. Reaction of di-n-butyl tert-butylperoxy phosphate (1, R — n -C i H 9) with cyclohexylamine and galvinoxyl. D eterm ination of the volatile products A solution of 7.05 g (0.025 mol) di-n-butyl tert-

butylperoxy phosphate, 1.05 g (0.0025 mol) galvinoxyl, 4.92 g (0.05 mol) cyclohexylamine, and 25 ml benzene was heated under nitrogen at 65 °C for 4 h. Nitrogen was gently bubbled through the reaction m ixture for 1 h and 1.2 g of a benzene solution of the volatile products was collected in a tap a t — 78 °C. Analysis of this solution by glc on Porapak Q showed it to contain (% yield) water (1.6%), m ethanol (4%), acetone (0.8%), tert-butanol (9%), and an unidentified component in trace amounts. The analogous reaction of a solution of 14.1 g (0.05 mol) di-w-butyl tert-butylperoxy phosphate, 4.95 g (0.05 mol) cyclohexylamine, and 50 ml


G. SOSNOVSKY E T A L . • REACTIONS OF DIALKYL tert -BUTYLPE R OX Y PHOSPHATES

benzene a t 65 °C for 24 h yielded as identified by glc analysis (% yield) water (0.7%), methanol (1.5%), acetone (0.7%), and Jeri-butanol (1.4%). Reaction of diisopropyl phosphate (6, R = i - C ZH 1) with diisopropyl N-cyclohexylphosphoramidate (4, R — i-C 3H 7; R' = cyclo-C6H 1XJ

A mixture of 2.73 g (0.015 mol) diisopropyl phosphate, 3.96 g (0.015 mol) diisopropyl N-cyclo hexylphosphoramidate, 4 ml water, and 30 ml benzene was stirred a t 60 °C for 24 h and was concentrated. Sublimation of the residual oil at 50 °C (0.1 mm) yielded 3.6 g (99%) diisopropyl N-cyclohexylphosphoramidate and extraction of the sublimation residue with ether yielded 2.73 g (100%) diisopropyl phosphate. Reaction of diisopropyl tert-butylperoxy phosphate (1, R = i-C 3H 7) with cyclohexylamine in the pres ence of diisopropyl N-cyclohexylphosphoramidate (4, R = i-C zH i; R ' = cyclo-C6H X1) in benzene at 60 °C

A solution of 4.57 g (0.018 mol) diisopropyl ter£-butylperoxy phosphate, 4.7 g (0.018 mol) diisopropyl N-cyclohexylphosphoramidate, 1.86 g (0.018 mol) cyclohexylamine, and 30 ml benzene was stirred at 60 °C for 24 h and was then con centrated. Crystallization of the residual oil from acetone yielded 3.2 g (63%) diisopropyl cyclohexylammonium phosphate. The mother liquor was concen trated. Crystallization of the residue from a mini mal amount of ether a t — 70 °C yielded 1.8 g (38%) diisopropyl N-cyclohexylphosphoramidate.

731

0.002 mol of the additive, where required, were stirred at the tem perature specified for 20 min under nitrogen. Then 1.98 g (0.02 mol) cyclohexyl amine was injected and heat was applied. Aliquots (0.5 ml) were titrated for peroxide content periodi cally. a. At 73 °C a solution of peroxyester (1) in benzene contained 96% of the peroxide after 3 h. b. At 73 °C a solution of peroxyester (1) and the amine in benzene contained no titratable peroxide after 1 h. c. At 73 °C a solution of peroxyester (1), the amine, AIBN, and benzene contained 95% of the peroxide after 3 h. d. At 73 °C a solution of peroxyester (1), the amine, galvinoxyl, and benzene contained no peroxide after 0.25 h. e. At 30 °C a solution of peroxyester (1), the amine, and benzene contained 85% of the peroxide after 1 h. f. At 30 °C a solution of peroxyester (1), the amine, galvinoxyl, and benzene contained 33% of the peroxide after 1 h.

B. Analogous reactions using diisopropyl tertbutylperoxy phosphate (1, R = i- C 3H 7), the addi tive, and benzene were performed at 73 °C. a. A solution of 0.005 mol peroxyester (1), 0.005 mol amine, and 10 ml benzene contained 68% of the peroxide after 40 min. b. A solution of 0.005 mol peroxyester (1), 0.01 mol amine, 0.0006 mol AIBN, and 10 ml benzene contained 75% of the peroxide after Effect of galvinoxyl, azobisisobutyronitrile ( A I B N ), 40 min. and 2,6-di-tert-butyl phenol on the reactions of dialkyl tert-butylperoxy phosphates (1 , R = C 2H 5, c. A solution of 0.005 mol peroxyester (1), i-C 3H 1) with cyclohexylamine. General procedure 0.108 mol amine, 0.0013 mol 2,6-di-£erf-butyl A. Solutions of 2.26 g (0.01 mol) diethyl tert- phenol, and 10 ml benzene contained 37% of the butylperoxy phosphate, 10 ml benzene, and peroxide after 40 min. 1 C. L. W h e e l e r , P B 119887, U .S . D ep t, o f Com merce, A ug. 1944. 2 B . G e h a u f , A nal. Chem. 29, 278 [1957]. 3 D . J. M a r s h , C h e m . I n d . 1956, 494. 4 L . L a r s s o n , A cta Chem. Scand. 12, 723 [1958]. 5 J. E p s t e i n and V. E . B a u e r , A bstracts o f the P ittsburgh Conference on A nalytical C hem istry and A pplied Spectroscopy, p. 24, F eb . 27, 1956. 8 G. A k s e n e s , A c t a Chem. S c a n d . 14, 2075 [I960]. 7 J. E p s t e i n , M. M. D e m e k , and D . H. R o s e n b l a t t , J. Org. Chem. 21, 796 [1956]. 8 A. R i e c h e , G. H i l g e t a g , and G. S c h r a m m , Chem. Ber. 95, 381 [1962]. 9 E . B o y l a n d a n d D . M a n s o n , J. Chem. Soc. 1957, 4689. 10 E . H. Z a r e t , P h. D . Thesis, U n iversity o f W isconsinM ilwaukee, 1974. 11 A. G a s i e c k i , M. S. T hesis, U n iversity o f W isconsinM ilwaukee, 1971. 12 a R . F . Collins, Chem. Ind. 1957, 704; b G. L. B e i c h l , J. E . C o l w e l l , and J . G. M i l l e r , Chem. Ind. 1960, 203.

13 C . J. B i a s e l l e a n d J. G . M i l l e r , J . A m e r . C h e m . S o c . 96, 3813 [1974], a n d r e f e r e n c e s t h e r e i n . 14 H . E . D e L a M a r e , J . O r g . C h e m . 25, 2114 [I9 6 0 ]. 15 J. O . E d w a r d s , i n “ P e r o x i d e R e a c t i o n M e c h a n i s m s , ” p. 98, J. O . E d w a r d s , E d . , I n t e r s c i e n c e P u b l i s h e r s , N e w Y o r k , 1962, a n d r e f e r e n c e s t h e r e i n . 16 A . K . H o f f m a n , A . M . F e l d m a n , E . G e l b l u m , a n d W . G . H o d g s o n , J. A m e r . C h e m . S o c . 8 6 , 639 [1964]. 17 E . G . R o z a n t s e v a n d V . D . S c h o e l l e , S y n t h e s i s

1971, 406. 18 P . D . B a r t l e t t , in “ P e r o x i d e R e a c t i o n M e c h a n i s m s , ” p. 4, in J. O . E d w a r d s , E d . , I n t e r s c i e n c e P u b l i s h e r s , N e w Y o r k , 1962. 19 A . Z w i e r z a k , B u l l . A c a d . P o l . S e i . , S e r . S e i. C h im .

11, 333 [1963]. 20 G . S o s n o v s k y a n d E . H . Z a r e t ,

J. O rg. C h em . 8 4 ,

968 [1969]. 21 G . S o s n o v s k y a n d E . Z a r e t , S y n t h e s i s 1972, 202. 22 L . S . S i l b e r t a n d D . S w e r n , A n a l . C h e m . 30 , 385

[1958].
