06-29-00 13:07
No 22772
Can somebody get this journal ref for us? My library doesn't have it to my knowledge.
Devakumar, C.; Mukerjee, S. K.; Indian J. Chem. Sect. B, Vol 25, 1986, 1150-54
It contains reactions of allylbenzenes with HBr at 0°C in only two hours, in up to 95% yields! Anybody interested in what solvents they used for this reaction?
, so somebody has to get it for us and post the procedure!
(Hive Bee)
06-29-00 21:54
No 22904
Is this a procedure for the productio of the 2-bromo or dibromo compound?
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(Moderator)
06-30-00 02:21
No 22988
2-bromopropane...
(Hive Bee)
06-30-00 20:30
No 23333
I think your reference is going to be very much like this one: Kropp, P.J., K.A. Daus, M. W. Tubergen, et al., J. Am. Chem. Soc., 1993, 115, 3071.
Surface-mediated reactions. 3. Hydrohalogenation of alkenes.
I had a discussion on the old board with someone about it. The article uses HCl in CH2Cl2 with silica or Al2O3 as the catalyst. The yields are excellence from what I remember, and react time quick. It seemed to me that the addition of water really fucked things up though. I could be wrong, maybe someone should check out that article agian and post it for good measure, maybe some can get some use out of it.
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(Stranger)
07-02-00 22:22
No 23995
ok... so i looked up the ref and hears the intersting stuff in it:
the paper talkes about makeing a new analogue of a insecticide,
so most of it is not to too relivent.
#12 is safrole, with a "stright" propyl chain, and a -OH atached imiditaly after the propyl chain going clookwise around.
#15 has the -OH in the 1 posistion, and the doble bond on the propyl chain is rotated so it points down.
"Attempts to induce direct cyclisation of 12-15 by Adams method
did not succeed due to the facile fission of the methylenedioxy
group under HBr-AcOH treatment. However, the methylenedioxy
group was stable upto 2hr in the presence of dry HBr in non-polar
solvents such as CHCl3 ....."
theirfor water is very bad for the reaction...
and
"reaction of o-allylphenols (12,15) with HBr-AcOH
aqueous Hbr (48% .2ml) was added to a solution of the phenol 12 (100mg)
in gl. AcHO (1ml) till the whole mixture became turbid. The mixture was
warmed on a water bathe for 30-45 min at 50-60 c., diluted with water (10 ml)
and fractionated into phenolic and neutral portions. the latter portion amounted
to hardly 5% while the pheonolic part was mlstly polymeric in nature and contained
only traces of the starting phenol (12). variation in the reaction period and
temperature did not help in inducint cyclisation of the allylphenols. for examlpe
phenol 12 could be recovered as such following the above treatment at 0c for
1hr as well as keeping the reaction mixture at room temp. for 1/2hr."
ok, dont use this...
so now the goood stufff.....
" reaction of o-allylphenols (12,15) with dry HBr
a solution of the appropriate o-allyphenol (1mmol)
in dry CHCl3 (15ml) at 0c was saturated with HBr.
after keeping for 2hr, the reaction mixture was poured
into ice water (50ml), the CHCl3 layer washed wit hwater till neutral
dried (Na2SO4) and evaporated to furnish the corresponding o-(2'-bromopropyl)phenol
in >95% yield as a dark brown liquid. the o-allylphenols, thus prepared, showed
IR absorption at 3550 (Br, OH) and #$00 (bonded OH), and characterstic
PMR signals at 1.65 (d,j =7.5 hz, 3H, CHBrCH3) 3.15, 3.20 (d,j=7.5, 2h, benzylic protons,)
4.3-4.5 (m, 1H, -CHBrCH3), 4.5-5.7 (Br s, !h, OH).
they were used as such without further purification in the following reaction..."
the product has the -OH in the same posistion as #12, irregardliss of the precursere..
since this workes with the phenols, why would it not work with normal safrole?...
(Moderator)
07-04-00 11:39
No 24572
Gnasher, there must be more in there. Dillapiole specifically.
(Stranger)
07-04-00 23:04
No 24769
is this what you where refering to?...
"... while the treatment of dillapiole with dry HBr gave a mixture of 1 and the bromopropyl derivative (19) in CHCl3, it exclusively led to 19 in DFM medium..."
intersting.... when 12 and 15 where treated in with dry HBr in CHCl3, the bromopropyl derivative was the main product (over 95%)....
hears the exp. procedur...
" 6-(2'-bromopropyl)-4,5-dimethoxy-1,3-ben
Dillapiole [4,5-dimethoxy-6-(2'propenyl)-1,3-benzod
(Moderator)
07-05-00 12:20
No 24995
Y E S !!! DMF is it!
And CHCl3 doesn't sound too bad either, at least for the phenols. Guess it will work just the same.
"Attempts to induce direct cyclisation of 12-15 by Adams method did not succeed due to the facile fission of the methylenedioxy group under HBr-AcOH treatment. However, the methylenedioxy group was stable upto 2hr in the presence of dry HBr in non-polar solvents such as CHCl3 ....."
That means forget about AcOH/HBr! It won't work.
Thanks Gnasher!
(Hive Bee)
07-06-00 03:21
No 25268
Some one should check out that reference that I posted earlier.
It looks like it will add some more good info to the table. Some one should also scan or quote that other article I'm interested in it and I'm sure Rhodium would be interested as well...
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(Stranger)
07-06-00 05:21
No 25322
There really is no point to fussing around w/ nasty HBr(g) solutions in DMF, AcOH, DMSO, etc to make bromosafrole.
This procedure works perfectly for smaller quantities of the 2- brompropane. The thermal decomposition isn't much fun to deal with in quantities greater than 50g.
Synthesis of 1-(3,4 methylenedioxyphenyl)-1,2-dibromopropane
18ml 48%HBr(aq), 10ml dH2O and Isosafrol(4.2g, .0258mol)is dissolved in 10ml ethyl ether with vigorous mag stirring. Rxn is chilled to -10'C (salt/ice bath). N-bromosuccinimide (4.6g, .0258mol) is slowly added portionwise over 10min and stirring is continued an additional 5min. Stirring is stopped and phases are separated. Aqueous layer is re-extracted w/ 10ml additional ether. Organic phases are combined, washed with 10ml 10% sodium bicarbonate then 10ml saturated NaCl soln and finally evaporated to yield 8g of title product as a thick greenish oil(90-96% yield). Product does not yield a solid crystal with any known crystallization solvent and also decomposes upon heating/distillation therefor is best characterized as the monobromocompound.
2-Bromosafrole
The above produced dibromo compound is carefully thermally decomposed in a standard vacuum distillation rig using an oil bath. Since copious quantities of HBr are produced as decomposition product it only make sense to use a water aspirator as vacuum source. When pot contents reach approximately 100' C dehalogenation takes place and 2-bromosafrole starts to distil over. Depending on vacuum, rxn. may start at lower temp. Do not allow pot contents to excede 130'C or glassware will rapidly fill with charcoal from uncontrolled decomposition! Yield of water white 2-bromosafrole was found to be in the 80-90% range.
Another thing, I'm not much of a U. Fester fan however I must give him credit for his bromosafrole rxn. which uses HCl to dehydrate 48%HBr. It really does work exactly as he describes it! Yields are high w/ very little unreacted safrole to separate from product and it can be scaled to any size imaginable.
(Moderator)
07-06-00 13:21
No 25443
??? When you thermally decompose dibromosafrole you will not produce the bromopropane, but a bromopropene! This is a completely different substance and cannot be used for our purpose!
R-CHBr-CHBr-CH3 ---heat---> R-CH=CBr-CH3 !!!
(Chief Bee)
07-06-00 14:20
No 25454
If you would react the 2-bromopropene with methylamine, you would get an enamine, which would rearrange to the imine, right?
http://rhodium.lycaeum.org
(Moderator)
07-06-00 16:16
No 25476
I'd rather react the bromopropene with NaOH to produce MDP2P, and save the MeNH2 for the reductive amination.
Anybody willing to try this DMF procedure out? It really sounds promising. Only drawback seems to be the use of gaseous HBr, but H3PO4/NaBr should take care of that. 95% in only 2 hrs, what else can you expect from a procedure?
(Moderator)
07-07-00 00:03
No 25611
Herr Ritter, could you post this bromosafrole procedure from Uncle Fester? Upscalable reactions look allways promissing for some of us with that special evil mindset. LT/
WISDOMwillWIN
(Stranger)
09-15-00 05:22
No 52308
I wonder if straight-up 48% HBr in DMF would work in this reaction?
In any case, I have to agree with you, Osmium. HBr in either DMF or CHCl3 is most likely the way to go!
--PK
(Hive Bee)
07-14-01 03:05
No 190478
Actually, Osmium was correct, there’s far more of interest about rearrangements, a matter very important to the bees. In particular the previous paper published by the same group is very important in gaining understanding:
Synthesis of New Analogues of Furapiole, a Potent Insecticide Synergist
C DEVAKUMAR & S K MUKERJEE
The synthesis of seven new analogues of furapiole (6,7-dihydro-4-methoxy-6-methylfuro [2; 3,f]-1,3-benzodioxole) is described. The methoxy analogue has been obtained by Vilsmeier formylation of furapiole followed by Baeyer-Villiger oxidation and methylation. The angular analogue has been prepared from dillapiole in four steps. 4-Allyloxy-2-hydroxyacetophenone when refluxed in DMA-PTS medium gives the coumaran derivative which on Dakin oxidation followed by methylation furnishes 4,5-dihydro-5-methylfuro [3,2,e]-1,3-benzoidioxole. The synthesis of other analogues is best accomplished from the appropriate o-allylsesamols through Hydrogen bromide addition followed by Adams method of cyclisation of the intermediates. Bioassay studies have shown these as highly-potent pyrethrum synergists.
Furapiole is a new potent synergist for pyrethrum and carbamate insecticides. Its formation from dillapiole mediated by Hydrogen bromide involves an unusual selective demethylative cyclisation. In an earlier communications, we have postulated a mechanism for this reaction and supported with studies on a large number of structural variants.
The unusually high biological activity of furapiole is not easily understandable even though a great deal of structure-activity relationship (SAR) studies have been made on its derivatives and open chain analogues Since furapiole is the first example of a methylenedioxy-alpha-methyldihydrobenzof
The synthesis of 6,7-dihydro-4, 8-dimethoxy-6-methylfuro [2,3-f]-1,3-benzodioxole was accomplished from furapiole. Bromination of furapiole gave the bromofurapiole in a quantitative yield. Attempts to convert bromofurapiole into 6,7-dihydro-4,8-dimethoxy-6-methylfuro [2,3-f]-1,3-benzodioxole by direct methoxylation using sodium methoxide either in dimethylformamide containing Cu2I2 or by the recent procedure of Marchand et al employing Cu2Cl2-pyridine-methanol under reflux, failed. In an indirect approach, Vilsmeier formylation of furapiole using N-methylformanilide-POCl3 complex gave the formylfurapiole in 60% yield. The presence of formyl group in formylfurapiole was indicated by its IR absorption at 1670 cm -1 and a one-proton singlet at 6 10.0 in its PMR spectrum in which the chemical shifts of OCH3 and - OCH2O- protons appeared downfield by <5 0.1 in comparison to those in furapiole. Baeyer-Villiger oxidation of the aldehyde by performic acid afforded the phenol in 50% yield, methylation of which furnished the analogue in a quantitative yield. The PMR spectrum showed a six-proton singlet at 5 3.90 for the two methoxyls in accordance with the structure.
The syntheses of the analogues were achieved by elaboration of dihydrofuran ring from the corresponding benzodioxoles. The synthetic approach as outlined involved Hydrogen bromide addition to the corresponding o-allylsesamols to give the o-(2'-bromopropyl)-sesamols as intermediates followed by Adams method of base catalysed cyclisation of the latter to the dihydrofurans. While the known allylphenols were prepared by the reported procedure, the new phenols were obtained by Claisen migration of the corresponding allyloxybenzodioxoles . Attempts to induce direct cyclisation of the phenols by Adams method did not succeed due to the facile fission of methylenedioxy group under Hydrogen bromide-AcOH treatment. However, the methylenedioxy group was stable up to 2 hr in the presence of dry Hydrogen bromide in non-polar solvents such as chloroform [Chloroform] and the indirect route was, therefore, preferred. The bromophenols thus obtained, on refluxing with acetone-potassium carbonate [K2CO3] furnished the required analogues respectively in 80-85% yields. The usual method of heating with pyridine, on the other hand, gave mixtures containing o-(1-propenyl)-phenols due to dehydrobromination in addition to the desired cyclised products.
A combination of the above two approaches enabled the synthesis of the angular methoxy analogue. While the treatment of dillapiole with dry Hydrogen bromide gave a mixture of furapiole and the bromopropyl derivative in chloroform [CHCl3], it exclusively led to the bromopropyl derivative in DIMETHYLFORMAMIDE medium. Formylation of the bromopropyl derivative as in the case of furapiole gave the bromoaldehyde in about 40% yield. Performic acid oxidation of bromoaldehyde gave the formyl ester which on refluxing with acetone-POTASSIUM CARBONATE underwent ester cleavage and intra-molecular cyclisation with the side chain, leading to the formation of .the analogue The PMR spectrum of analogue showing two singlets of three protons each at 53.75 and 3.93 established the angular fusion of fur|n ring.
4,5-Dihydro-5-methylfuro [3,2-e]-1,3-benzodioxole was synthesised. o-Hydroxyallylacetophenone on refluxing in N,N-dimethylaniline containing p-toluenesulfonic acid underwent a single-pot Claisen rearrangement and cyclisation to the coumaran in 60% yield. Dakin oxidation of the coumarin gave the catechol in about 30% yield. The poor yield of the catechol was due to the formation of a mixture of polar products. A re-scanning of literature at this point revealed that 5-hydroxy-2,3-dihydrobenzofurans of this type are highly unstable in the presence of alkaline hydrogen peroxide [H2O2], their most characteristic reaction being facile oxidation to quinones with the fission of the heterocyclic ring. Methylenation of 2, 3-Dihydro-4,5-dihydroxy-2-methylbenzofur
The bioassay studies of the compounds as pyrethrum synergists against red flour beetles (Tribolium casteneum Herbst) using our earlier techniques have shown that the linear analogues are highly active, the respective factors of synergism being 5.2,6.3 and 4.6. It implies that furo [2,3-f]-l,3-benzodioxoles are per se better pyrethrum synergists than simple 1,3-benzodioxoles, and additional methoxy substituents have an enhancing effect on this ring system as observed in other cases.
Experimental Procedure
8-Bromo-4-methoxy-6-methyl-6,7-dihydrofu
Bromine (0.1 ml) in chloroform [CHCl3] (20 ml) was added dropwise to a solution of furapiole (415 mg) in chloroform [CHCl3] (20ml) till the pale yellow colour of bromine persisted. After 1 hr, the solvent was evaporated and the residue (560 mg) crystallised from methanol to give colourless needles
8-Formyl-4-methoxy-6-methyl-6,7 dihydrofuro[2,3-f]-1,3-benzodioxole
N-Methylformanilide (11.2g) was mixed dropwise with phosphoryl trichloride [POCl3] (11.5g) in dry chlorobenzene (10 ml) at 0°.after keeping for 1 hr, the mixture was added to furapiole (10.6g) in chlorobenzene (20 ml) at 0°, stirred at 20° for 6 hr and heated at 60-70° for 8 hr. It was then poured into ice-water (100 ml), the organic layer washed free of acid and dried over anhydrous sodium sulfate [Na2SO4]. Dilution of the organic layer with hexane followed by chilling precipitated the aldehyde which was recrystallised from hexane-benzene (95:5) as light yellow needles (7.1 g), m.p. 101-2°
6,7-Dihydro-4-methoxy-6-methylfuro[2,3]-
Baeyer-Villiger oxidation of 8-Formyl-4-methoxy-6-methyl-6,l dihydrofuro[2,3-f]-l,3-benzodioxole (4.72g) with performic acid using the procedure described for sesamol gave the phenol which was crystallised from cyclohexane as white plates (2.35 g), m.p. 89-90°
6,7-Dihydro-4,8-dimethoxy-6-methylfuro-[
Methylation of the above phenol (1.12g) with methyl iodide [MeI] (1.5 ml) in dry acetone (50 ml) containing anhydrous potassium carbonate [K2CO3] (1.4g) under reflux for 4 hr furnished the methoxyfurapiole (1.12 g) which was recrystallised from methyl alcohol [MeOH] as white needles, m.p. 47°
6-(2'-Bromopropyl)-4,5-dimethoxy-1,3-ben
Dillapiole [4,5-Dimethoxy-6-(2'-propenyl)-1,3-benzo
6-(2'-Bromopropyl)-4,5-dimethoxy-7-formy
Vilsmeier formylation of 6-(2'-Bromopropyl)-4,5-dimethoxy-1,3-ben
6-{2'-Bromopropyl)-4,5-dimethoxy-7-formy
The above aldehyde (6.62 g) was oxidized with performic acid at - 5° for 16 hr as described earlier for 6,7-Dihydro-4-methoxy-6-methylfuro[2,3]-
5,6-Dihydro-7,8-dimethoxy-5-methylfuro-[
The formyl ester (1.04g) was refluxed in dry acetone (50 ml) containing anhyd. potassium carbonate (0.5 g) on a water bath for 6-8 hr. The completion of the reaction was monitored by TLC. The usual work-up gave a residue (650 mg) which was purified on a column of silica gel (20g) using hexane-benzene (3:1) as eluent to give 5,6-Dihydro-7, 8-dimethoxy-methylfuro[2,3-e]-1,3-benzod
o-Allylphenols
These were prepared by the Claisen rearrangement of 5-allyloxy-6-methoxy-1,3-benzodioxole and 6-allyloxy-4,5-dimethoxy-1,3-benzodioxol
4-(2'-Propenyl)-6-methoxy-1,3-benzodioxo
4-(2'-Propenyl)-6,7-dimethoxy-1,3-benzod
Reaction of o-allylphenols with Hydrogen bromide-AcOH A typical example is described below:
Aqueous Hydrogen bromide (48%, 0.2 ml) was added to a solution of the phenol (100 mg) in glacial acetic acid (1 ml) till the whole mixture became turbid. The mixture was warmed on a water-bath for 30-45 min at 50-60°, diluted with water (10 ml) and fractionated into phenolic and neutral portions. The latter portion amounted to hardly 5% while the phenolic part was mostly polymeric in nature and contained only traces of the starting phenol. Variation in reaction period and temperature also did not help in inducing cyfclisation of allylphenols. For example, the phenol could be recovered as such following the above treatment at 0° for 1 hr as well as keeping the reaction mixture at room temperature for 1/2 hr.
Reaction of o-allylphenols with dry Hydrogen bromide
A solution of appropriate o-allylphenol (1 mmol) in dry chloroform (15 ml) at 0° was saturated with hydrogen bromide. After keeping for 2 hr, the reaction-mixture was pouted into ice-water (50 ml), the chloroform layer washed with water till neutral, dried sodium sulfate (Na2SO4) and evaporated to furnish the corresponding o-(2'-bromopropyl)phenol in > 96% yield as a dark brown liquid. They.were used as such without further purification in the following reaction.
Preparation of furapiole analogues
o-(2'-Bromopropyl)phenols (1 mmol each) were refluxed separately in dry acetone (50 ml containing anhydrous potassium carbonate (140 mg, 1 mmol) on a water-bath for 5-8 hr and worked-up as described in the case of 6,7-Dihydro-4-methoxy-6-methylfuro[2,3]-
6,7-Dihydro-6-methylfuro[2,3-f]-1,3-benz
4,5-Dihydro-7-methoxy-5-methylfuro
4,5-Dihydro-7,8-dimethoxy-5-methylfuro [3,2-e]-1,3-benzodioxole: It was crystallised from MeOH as white plates, m.p. 38-39°
5,6-Dihydro-5-methylfuro[2,3-f]-1,3-benz
5-Acetyl-2,3-dihydro-4-hydroxy-2-methylb
4-Allyloxy-2-hydroxyacetophenone (3.8 g) was refluxed in dry N,N-dimethylaniline (40 ml) fortified with anhydrous p-toluenesulfonic acid (3g) for 4 hr and 90% of the aniline distilled off. The residue after cooling to room temperature was poured inter ice-water (50 ml) containing concentrated HCl (10 ml), and worked-up as usual to give 5-Acetyl-2,3-dihydro-4-hydroxy-2-methylb
2,3-Dihydro-4,5-dihydroxy-2-methylbenzof
A solution of 5-Acetyl-2,3-dihydro-4-hydroxy-2-methylb
4,5-Dihydro-5-methylfuro [3,2-e]-1,3-benzodioxole
Methylenation of 2,3-Dihydro-4,5-dihydroxy-2-methylbenzof
References .
1 Mukerjee S K, Walia S, Saxena, V S & Tomar S S; Agric Biol Chem, 46 (1982) 1277.
2 Walia S, Saxena V S & Tomar S S, Indian J Ent, (in press)
3 Devakumar C & Mukerjee S K, Indian J Chem, 25B (1986) 368.
4 Devakumar C, Saxena V S & Mukerjee S K (under communication)
5 Devalcumar C. Saxena V S & Mukerjee S K, Agric Biol Chem. 49 (1985)725. ,
6 McKillop A, Howarth B D & Kobylecki R J, Synth Commun. 4 (1974) 35.. ..
7 Manchand P S, Townsend J M, Belica P S & Wong H S. Synthesis, (1980) 410.
8 Arnold R T & Burdwell F, J Am Chem Soc, 64 (1942) 2983.
9 Baker. W & Savage R I, J Chem Soc, (1938) 1602.
10 Baker, W & Lothian O M, J chem Soc, (1935) 628.
11 Coffey S Rodd’s Chemistry of Carbon Compounds. Vol. 4, Part A (Elsevier Publishing Company, London) 1973, 169.
12 Clark J H, Holland H L & Miller J M, Tetrahedron Lett , (1976) 3361.
(Hive Bee)
07-14-01 19:05
No 190555
Selective Demethylative Cyclisation of 2-Methoxy-allylbenzene
C DEVAKUMAR & S K MUKERJEE
Treatment of 3-substituted 2-methoxyallylbenzenes with dry Hydrogen bromide in chloroform causes selective demethylative cyclisation to give 7-substituted 2-methyl-2, 3-dihydrobenzofurans. The reaction involves mutual participation of allyl and 2-methoxyl groups and is sterically accelerated by substituents vicinal to OCH3. The reaction does not take place in high dielectric solvents such as dimethylformamide or dimethylsulfoxide. A probable mechanism envisaging a non-classical ionic transition state is proposed and the synthetic utility of this reaction is also demonstrated.
In search for new insecticide synergists, we observed that furapiole derived from dillapiole, a waste product from oil of Anethum sowa Roxb, is an excellent potentiator of pyrethrum and carbamate insecticides. The formation of furapiole from dillapiole by Hydrogen bromide in dry chloroform in high yield at low temperature involved selective demethylation of the methoxyl group ortho to the allyl side chain followed by cyclisation in a concerted fashion. Selective demethylation of substituted anisoles under such mild condition is unique and deserves a more detailed investigation. In this paper, we report such an attempt with a large number of substituted o-allylanisoles in order to understand the mechanism and optimum require-ments of this reaction.
The 3-methoxyallylbenzenes used were made by the following standard route: phenols->allylphenyl ethers-> o-allylphenols-> o-allylanisoles. These were characterised by elemental and spectral data. Except the trimethoxyallylbenzenes and the naturally occurring allyl derivatives, sarisan and osmorhizole, the other o-allylanisoles reported now are new. Incidentally synthetic confirmation of the structure, of naturally occurring sarisan and osmorhizole is also reported herein for the first time.
The o-allylanisoles were treated with dry Hydrogen bromide in chloroform at 0° C for 2 hr and the products formed were separated by column chromatography and characterised by spectral data. The yields of products were estimated by HPLC (vide Experimental). Prolonging the reaction period beyond 2 hr did not improve either the yield or the ratio of products formed. Increase in temperature and reaction time for methylenedioxy-anisoles caused complications due to formation of polar compounds presumably arising by the cleavage of the methylenedioxy ring.
The results show that in the case of an highly substituted o-allylanisole, viz. 2,3-methylenedioxy-4,5,6-trimethoxyallyl
The HPLC analysis of the products from dillapiole, prepared as reported earlier, on the other hand showed that furapiole constituted only 80% of the total products. The normal Hydrogen bromide addition product was formed to the extent of 20% in this case.
Further reduction in the number of ring substituents such as in 2, 3, 4-trimethoxyallylbenzene.resulted in the corresponding coumaran and the normal addition product in 3:2 ratio.
The yield of the dihydrobenzofuran from 3-chloro-2-methoxyallylbenzene was only 40%. On the other hand, its dimethoxy analogue gave the coumaran in 30% yield only.
The o-allylanisoles gave exclusively the corresponding normal Hydrogen bromide addition products with no trace of cyclised products, showing that a substituent in 3-position, i.e. ortho to the methoxyl (and meta to the allyl group) was essential for this demethylation.
Dihydrodillapiole and its bromo derivative on similar treatment with dry hydrogen bromide, remained unaffected and did not give any demethylated product or furapiole showing that the allyl unsaturation was also essential for this demethylation.
All the title compounds gave, however, exclusively the normal Hydrogen bromide addition products without the formation of the corresponding dihydrobenzofurans when the reaction medium was changed to high dielectric solvent like dimethylsulfoxide or dimethylformamide.
It is clear from the above results that this unusual reaction in chloroform occurs in the case of only 3-substituted 2-methoxyallylbenzenes and the selectivity of this reaction depends entirely on the steric crowding of the environment vicinal to the 2-methoxvI function. The electronic nature of the substitutents seems to have little or no influence on this reaction pathway as is evident from the fact that both deactivating (CI) and activating (OCH3) substituents ortho (and not para) to 2-methoxyl lead to demethylation and formation of dihydrobenzofurans. The apparently better yield of the chlorocoumaran in comparison to that of its methoxy analogue is, therefore, due to the larger size of the chlorine atom producing greater steric acceleration in the parent anisoles respectively. The stability of dihydrodillapiole under these reaction conditions implies the role of neighbouring allyl group participation in demethylation.
The selectivity of the methoxyl function in undergoing demethylation and the neighbouring allyl group participation phenomenon observed in the above reactions seem to suggest the probable mechanism, via a non-classical ionic transition state involving both the lone pair of electrons of the methoxyl function and electrons of the allyl double bond after protonation. The formation of such transition state would be facilitated conformation-wise in 2-methoxyallylbenzenes bearing a substituent at position-3 while its stability would be retarded in polar aprotic solvents such as dimethylformamide or dimethylsulfoxide as corroborated by experimental evidence. The nature of products would then depend upon the direction of nucleophilic (Br -) attack on the transition state. The failure to detect o-allylphenols as intermediates and the stability of the co-products, viz. the brompopropylbenzenes on prolonging the reaction time further suggest that the demethylation and cyclisation processes might be concerted rather than sequential.
The potential synthetic utility of this reaction. The allylbenzene containing two methoxyls ortho to allylic function undergoes preferential demethylation of the sterically hindered 2-methoxyl alone to give 2,3-dihydro-4, 7-dimethoxy-2-methylbenzofuran. Starting from the same o-allylphenol, one could thus synthesise 2,3-dihydro-4,7-dimethoxy-2-methylbenzof
Experimental Procedure
The trimethoxyallylbenzenes were synthesised following the reported procedure:
2,3,4-Trimethoxyallylbenzene: Colourless oil, b.p. 128-30°/3 mm [reported 127-32°/3 mm]
2,4,5-TrimethoxyalIylbenzene: Colourless oil. b.p. 125-26°/10mm [reported 120°/5mm)]
2,3,6-Trimethoxyallylbenzene : Colourless oil. b.p. 118-119°/10mm
General procedure for preparation of other o-allylanisoles
The o-allylanisoles listed in the sequel were obtained by methylation of the corresponding o-allylphenols by CH3I-POTASSIUM CARBONATE-acetone method. Phenols in turn were prepared as reported earlier .
2,3-Methylenedioxy-4,5, 6-trimethoxyallylbenzene: Colourless oil; b.p. 135-7°/10 mm
3-Chloro-2-methoxyallylbenzene: Colourless oil; b.p. 102-3°/10mm
Sarisan: Colourless oil; b.p. 86-87°/0.5 mm
Osmorhizole : Colourless oil; b.p. 71-2°/2 mm
2,5-Dimethoxyallylbenzene: Colourless oil; b.p. 120-21°/10mm
5-Chloro-2-methoxyallylbenzene : Colourless oil; b.p. 115-16°/10 mm
General procedure for the reaction of Hydrogen bromide with o-allylanisoles
A current of dry Hydrogen bromide gas was bubbled through ice-cold solutions of o-allylanisoles (5 mmol) in dry chloroform (20 ml) till saturation. After 2 hr of standing at 0° C, the reaction mixtures were decomposed by pouring into ice-water (100 ml), the chloroform layer repeatedly washed with water till neutral, dried (Na2SO4 and concentrated to furnish light brownish oily residues (yield 95%). A small sample in each case was preserved for HPLC using authentic samples of the compounds obtained after purification of the reaction products. A portion of the product residue in ether was extracted with ice-cold 10% methanolic KOH to separate any phenolic product. In all the cases, no such product was formed in detectable amounts.
The TLC of the products revealed that some of the reaction products were binary mixtures while others were single. The individual components of the binary mixtures were separated by column chromatography as described below.
The product mixture from 2, 3, 4-trimethoxyallylbenzene (300 mg) loaded over silica gel (25 g) was eluted first with hexane (100 ml) followed by hexane-benzene (4:1, 5 x 60 ml and 1:1, 3 x 50 ml). Elution with hexane-benzene (4:1) furnished light brown oil (150mg) which was characterised as 1-(2-Bromopropyl)-2, 3, 4--trimethoxybenzene while elution with hexane-benzene (1:1) gave 2, 3dihydro-6,7-dimethoxy-2-methyl-2-methyl
Analytical grade products were obtained by passing the crude products through a short column of silica gel, eluting the column with hexane-benzene (9:1).
2, 3-Dihydro-6, 7-dimethoxy-2-methyl-4, 5-methylenedioxybenzofuran was obtained from 2, 3-methylenedioxy-4, 5, 6-trimethyoxyallylbenzene and it was found to be identical with a synthetic sample prepared earlier.
2,3-Dihydro-6, 7-dimethoxy-2-methylbenzofuran : Colourless oil
1-(2-Bromopropyl)-2,3,4-trimethoxybenzen
7-Chloro-2, 3-dihydro-2-methylbenzofuran: Colourless oil.
1-(2-Bromopropyl)-3-chloro-2-methoxybenz
1-(2'-Bromopropyl)-2,3-dimethoxybenzene:
2'-Bromopropyl)-2-methoxy-4, 5-methylenedioxybenzene: Colourless oil turning yellow on standing
Bromopropyl)2,4,5-trimethoxybenzene: Light yellow oil
1 -(2'-Bromopropyl)-2,4-dimethoxybenzene: Colourless oil,
Bromopropyl)-2,5-dimethoxybenzene: Colourless oil,
(2-Bromopropyl)-5-chloro-2-methoxybenzen
2,3-Dihydro-4,7-dimethoxy-2-methylbenzof
1-(2-Bromopropyl)-2,3,6-trimethoxybenzen
Reaction of o-allylanisoles with Hydrogen bromide in dimethylformamide or dimethylsulfoxide
An ice-cold solution of an o-allylanisole(100 mg) in dry dimethylformamide or dimethylsulfoxide (10 ml) was saturated with dry Hydrogen bromide and after 2 hr of standing was worked-up as described above. The products were found to consist only of the bromopropylbenzenes, whose characterisation data are given above.
1-(2'-Bromopropyl)-2,3-methylenedioxy 4,5,6-trimethoxybenzene; The Hydrogen bromide reaction of 2,3-methylenedioxy-4,5,6-trimethoxyallyl
2,3-Dihydro-4,5-dimethoxy-2-methyl-benzo
2-Allyl-3,4-dimethoxyphenol (200 mg) in glacial acetic acid (1 ml) was treated with 48% aq Hydrogen bromide (0.5 ml) and heated at 60-70°C for 3 hr over a water bath. The reaction mixture was poured into cold water (20 ml), extracted with ether (25ml), ethereal layer washed with 10 ml each of water, satd NaHCO3 solution and 10% methanolic NaOH and finally with water till neutral. The residue after evaporation of the solvent was passed through a short column of silica gel. Eluting the column with hexane-benzene (4:1) furnished 2,3-Dihydro-4,5-dimethoxy-2-methyl-benzo
References
1 Tomar S S, Maheshwari M L & Mukerjee S K, J Agric Fd Chem, 27 (1979) 549.
2 Walia S, Sauna V S & Tomar S S, Indian J Em, (in press).
3 Devakumar C & Mukerjee S K, Abst Nail Symp on Chemical Reaction Mech (Ujjain) (1983) 10.
4 Tarbell D S, Org Reactions, 2 (1946).
5 Rhoads S J & Raulins N R. Org Reactions, 22 (1975)
6 Shulgin A T, CanJ Chem, 43 (1965) 3437.
7 Kumanato J & Scora R W, J Agric Fd Chem, 18 (1970) 544.
8 Zwaving J H, Smith D & Bos R, Pharm Weekbl, 106(1971) 182 Chem Abst, 75 (1971) 1348e.
9 Saiki Y, Saito T & Fukushina S, YakugakuZassi,9»(\96T) 185; through Chem Abst, 69 (1968) 6700lu.
10 Arnold R T & BurdweU F, J Amer Chem Soc, 134 (1942) 2983.
11 Devakumar C & Mukerjee S K (communicated).
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(Hive Bee)
07-15-01 14:27
No 190732
lugh, the graphical version has got to bee better. I suppose those of us who grew up on Classics Illustrated versions of Ivanhoe and Treasure Island, just don't have the attention span to keep imagining these anomolous heterocyclic ring clotures looping themselves through all their acrobatics. Still, I'm glad the authors are trying to do something useful about all those useless constituents in the oil of Indian dill: "furapiole derived from dillapiole, a waste product from oil of Anethum sowa Roxb".
It is certainly a shame, that this waste product dillapiole, forms the majority constituent of the essential oil of the otherwise useful herb Matico. Other Piper species have useful substances in their essential oils, but this Piper aduncum, also known as Piper angustifolium, and by no less than twenty-five (!) other Latin binomials all referring to this one plant, is accursed by having an essential oil nearly all composed of this same waste product. No other plant has this useless dillapiole as a majority constituent, though Anethum sowa is blighted with a lot of it.
Gottlieb et al. (1981) studied the main components of the Brazilian varieties P. aduncum var. aduncum and P. aduncum var. cordulatum finding dillapiole as 74.5% and 88.4% respectively.
Gottlieb, O.R. M. Koketsu, M.T. Magalhães, J.G.S. Maia, P.H. Mendes, A.I. da Rocha, M.L. da Silva & V.C. Wiiberg. 1981. Oleos essenciais da Amazônia VII. Acta Amazonica 11: 143-148.
Gupta et al. (1983) investigated the composition of the essential oil of the fresh leaves of the plant collected in Panama finding dillapiole (90%) as majority component.
Gupta, M.P. T.D. Arias & R.M. Smith. 1983. The composition of the essential oil of Piper aduncum L. from Panamá. Rev. Latinoamer. Quím. 14: 36-37.
We might put Devakumar and Mukurjee on the job, of contorting the molecules of Matico pepper, in such fashion that vast areas of tropical America might become bug free for a long time.
turning science fact into <<science fiction>>