GRUPO 7: GRASAS, ACEITE Y MANTEQUILLA
E) DIAGNÓSTICO
4 .0 Introduction
The methods available for the synthesis of alkyl hydroperoxides can be divided into two general categories :
(1) those methods involving the alkylation of hydrogen peroxide
and (2) those methods involving direct oxygenation o f a suitable substrate.
These preparative routes have been considered in the General Introduction (Chapter 1) and consequently will not be considered here.
This chapter is concerned with the application of the alkylation method developed by Mosher and Williams ^ ^ to the preparation of some primary cyclopropyl alkyl hydroperoxides.
Mosher-Williams Preparative Route to Alkyl Hydroperoxides
The Mosher-Williams preparative route to alkyl hydroperoxides involves the alkylation o f 30% hydrogen peroxide with an alkyl methane sulphonate (eqn l)h
eqn 1
(1)
K GSO„l%* \
Hydrogen peroxide ( 30%, 1 equiv) is added to a cold solution o f the alkyl methane sulphonate dissolved in aqueous methanol. Potassium hydroxide (50%, 2 equivs) is then added dropwise and the mixture stirred for twenty-four hours. The temperature of the reaction mixture is maintained between 0 - 4 during the addition. The crude hydroperoxide is then isolated by means o f base extraction.
This preparative route has been reported to give good yields of hydroperoxides for primary substrates (Table 1)^ and has been extended to include the preparation of secondary alkyl hydroperoxides ^ (see Chapter 5).
Table 1 HYDROPEROXIDE YIELD n-amyl hydroperoxide 43% n-hexyl hydroperoxide 44% n-octyl hydroperoxide 38% n-nonyl hydroperoxide 39% n-decyl hydroperoxide 45%
Our results which are presented below describe the application of this particular preparative route to the preparation of one primary cyclopropyl alkyl hydroperoxide (1). We have been unable to develop this method into a general preparative route for the synthesis o f primary cyclopropyl alkyl hydroperoxides.
The structure o f com pound (1) was confirmed by means o f and nuclear magnetic resonance spectroscopy, positive peroxide test with acidic ferrous thiocyanate and by elemental analysis.
OOH
(1)
4.1 Results and D iscussion
I he following reaction schem e (Scheme I) was proposed for the preparation o f a series o f priman^ alkyl cyclopropyl hydroperoxides.
Scheme I y (» on O H osojMe. I'/I O O H Reaye.i^*"^ (■) M e S c x c i , p i^ r td m e , l " ) Z n ( c i A ) . t u ) i c X , 6 C % K O H R - L< L| (. , H
As has been described in Chapter 2 primary alkenyl alcohols cannot be cyclopropanated directly by the Simmons-Smith cyclopropanation reaction because a large number of by-products are generated during the reaction. This problem may be overcome by modilying the -OH group to reduce its nucleophilicity. Accordingly the cyclopropanation reaction has been extended to include alkenyl methanesulphonates (see Chapter 2).
OSG.Me
.Me OSO^Me
(2)
The alkenyl methanesulphonatc (2) was prepared by treating 3-methyl-3-buten-1 -ol with methanesulphonyl chloride (1 equiv) and excess pyridine. The corresponding cyclopropanated analogue was prepared by means of the Simmons-Smith cyclopropanation reaction as described in Chapter 2.
The cyclopropyl methanesulphonatc (3) was obtained as a 1:1 mixture with the conesponding umeacted alkenyl methane sulphonate (2) (eqn2) (see Chapter 2).
Attempts to separate the two compounds (2) and (3) by silica column chromatography were unsuccessful. Consequently the mixture of compounds (2) and (3) was treated with 30% hydrogen peroxide and 50% potassium hydroxide in aqueous methanol in order to prepare the hydroperoxides (1) and (4) (eqn3).
(3) (2) UMe O S O „ M e (1) (4)
We correctly anticipated that compound (4) would react faster than compound (1) with mercury(II) acetate and were therefore able to separate the two hydroperoxides as is described below:
The mixture of peroxides (1) (1 equiv), and (4) (1 equiv), was dissolved in anhydrous dichloromethane, (15 ml) and mercury(II) acetate (1 equiv) added. After approximately thirty minutes all of the mercury acetate was consumed in the reaction. The reaction mixture was then concentrated to approximately one half of its original volume by means of a rotaiy evaporator. On cooling a white solid crystallised out. Pentane (15 ml) was then added and the the mixture filtered. The solid material was disgarded. The filtrate was dried over anhydrous sodium sulphate and the solvent removed to yield the crude cyclopropyl alkyl hydroperoxide. The cyclopropyl alkyl hydroperoxide was purified by silica column chromatography (dichloromethane as the
eluent).
Its structure was confirmed by means of and nuclear magnetic resonance spectroscopy, positive peroxide test with acidic ferrous thiocyanate and elemental analysis.
Attempts to extend this method to include the preparation o f other primary cyclopropyl hydroperoxides (5) - (6) failed consistently and on each occasion only unreacted methanesulphonate was recovered.
O '
OOH
a )
More discouragingly we were not able to repeat the preparation o f compound (1) and only unreacted mesylate was recovered. It must therefore be concluded that the preparative route to hydroperoxides developed by Mosher and Williams cannot be extended to include the synthesis of primary cyclopropyl alkyl hydroperoxides
Chapter 4
E4.1 Preparation O f Methane Sulphonates
Pyridine (0.116 mol) was added dropwise over 2 hours to a stirred mixture of the alkenyl alcohol (0.058 mol) and and methane sulphonyl chloride (0.058 mol) in an atmosphere of nitrogen. During the addition the mixture was cooled by means of an ice-water bath. Stirring was continued for a further two hours.
Cold hydrochloric acid (20%, 15 ml), was then poured onto the cold reaction mixture, a pale yellow solid, which dissolved upon addition of the acid. The organic product was extracted with diethyl ether (3x15 ml). The combined ether extracts were washed with saturated sodium chloride (2x15 ml) and saturated sodium bicarbonate (2x15 ml) solutions successively and dried over anhydrous sodium sulphate. The solvent was removed at a rotaiy evaporator to yield the crude product.
N.M.R. data for mixed mesvlate
5 c ( C D C l 3 , 5 0 M H z ) : 12.49 , 12.62 , 22.28 , 22.51 , 38.27 , 37.26 , .7.36 , 36.90 , 67.87 68.62 , 113.16, 140.05
E4.2 Preparation o f Hydroperoxides
The crude mixture of methane sulphonates ( approximately 0.01 mol alkenyl mesylate and 0.01 mol cyclopropyl mesylate) was dissolved in methanol (40 ml) and cooled in an ice bath. Cold hydrogen peroxide (30%, 0.04 mol) was then added to the mixture
this was followed by the dropwise addition of cold potassium hydroxide (50%, 0.02 mol). The reaction mixture was cooled in an ice-water bath throughout the addition. The mixture was stirred over twenty-four hours and allowed to warm up to room temperature.
The reaction mixture was cooled in an ice-water bath and cold potassium hydroxide (50%, 50 ml) added. The mixture was extracted with benzene. The aqueous layer was neutralised with 2M hydrochloric acid and the hydroperoxide extracted with benzene. The benzene extract was extracted with 25% potassium hydroxide (2x15 ml). The basic solution was neutralised with 2M cold hydrochloric acid and the organic product extracted into diethyl ether (3x15 ml). The combined ether extracts were dried over sodium sulphate and the solvent removed at a rotary evaporator to yield the crude product.
N.M.R. Data For Mixture O f Peroxides
3-Methyl-3-butenyl-l-hydroperoxide
5h(CDC1 3,200MHz) : 1.74(3H,s), 2.34(2H,t,J=6.74Hz), 4.08(2H,t), 4.72(2H,m), 8.75(lH,br.s)
Literature Values:
Sj/CDCÏ3,400MHz) : lJ4(3H,s), 2.34(2H,t,J=6.30Hz), 4.08(2HxJ=6.31Hz), 4.72(2H,m) 0c(CDCl^}OOMHz) : 22.39, 35.78, 75.04, 112.01, 142.12 l-Hydroperoxy-3-methyIcyclopropane 6h(CDC1 3,200MHz) : 0.00(4H,m), 1.00(3H,s), 1.72(2H,t), 4.33(2H,m), 8.75(lH,br.s) 8c(CDCl3,50MHz) : 12.76, 14.97, 22.84, 36.80, 75.61E4.4 Separation o f cyclopropyl and alkenvl hydroperoxides
The mixture of peroxides, consisting of approximately 7.5 mmol alkenyl hydroperoxide and 7.5 mmol cyclopropyl alkyl hydroperoxide, was dissolved in anhydrous dichloromethane, (15 ml) and mercury(II) acetate (7.5 mmol) added. After approximately thirty minutes all of the mercury acetate was consumed in the reaction. The reaction mixture was then concentrated to approximately one half of its original volume by means of a rotaiy evaporator. On cooling a white solid crystallised out. Pentane (15 ml) was then added and the the mixture filtered. The filtrate was dried over anhydrous sodium sulphate and the solvent removed to yield the crude cyclopropyl alkyl hydroperoxide. The cyclopropyl alkyl hydroperoxide was purified by silica column chromatography (dichloromethane as the eluent).
l-Hvdroperoxv-3-methvl Cyclopropane (1)
Ô h(C D C13 400M H z) : 0 .2 4 (4 H ,m ), 1 .0 0 (3 H ,s), 1 .5 2 (2 H ,t,J= 7 .0 1 H z ), 4.10(2H,t,J=7.02Hz), 8 .5 0 (lH ,br.s)
Sc(CD C l3,1 0 0M Hz) : 12.83, 13.02, 22.91, 36.87, 77.32 ./Analysis Required for Q H13O2 : C : 61.52 H : 11.18
Found for C ^H |3 0 2: C ; 61.74 H : 11.24
References
in M osher and kVViliams , J.A m .Chem .Soc., 76, 2984, (1954). 2xM osher and Williams. J.A m .Chem .Soc., 76, 2987, (1954). 3. II.E.Sim mons R.D. Smith, J.A m .Chem .Soc., 16, 1337, (1964). See also Chapters 1 & 2