Piperonal -- mda/mdma?

Bluechip · Mon Feb 28, 2005 5:23 am

What are some methods I could look up for this please?

ApprenticeCook · DILLIGAF

Your kidding right?
There are heaps, check the rhodium mirror...
This is not a place for repetition of already availible information, if you have a question about the synthetic method(s) you research then you may ask...

-AC

IndoleAmine · Dreamreader Deluxe

We need something like "UTFSE" I think... Laughing

piperonal + nitroethane -> 1-(3,4-methylenedioxyphenyl)-2-nitropropene (MDP2NP)

MDP2NP + Fe + CH3COOH -> 1-(3,4-emthylenedioxy-phenyl)-2-propanone (MDP2P)

MDP2P + CH3NH2 ---Al/Hg--> MDMA
(or MDP2P + NH3 ---Al/Hg--> MDA

alternatively:

piperonal + nitroethane -> MDP2NP

MDP2NP --LAH--> MDA

i_a

Blind Angel · Mon Feb 28, 2005 7:52 pm

And why not

MDP2NP -Al/Hg-> MDMA

It would be a lot easier and OTC than using LAH, or am I missing something?

MistaMiyagi · Dream Team

I will post what I believe to be the most OTC route for this rxn soon...

Just got to find time to format it appropriately for posting... It's midterm week right now and I am tearing my hair out.

MM

nyarlothotep · Mon Feb 28, 2005 8:20 pm

Al/Hg reduction on the nitropropene would yeild MDA, not MDMA, seeing as there is no methyl group attachet to the nitrogen.
discussion of Al/Hg nitropropene rxn's here:

https://synthetikal.com/synthforum/viewtopic.php?t=304&postdays=0&postorder=asc&start=15

Seems like it would work, but a test with MDA as the goal failed, apparently.
Missing Rhodium file regarding that has been posted at the end of the thread.

MM: SWIN'll be waiting with eyes peeled and hands wringing wetly for that post.....and will look into Al/Hg mechanics more in depth.
He really wants this to work.....even if it has to be tweaked.....

ApprenticeCook · DILLIGAF

From rhodiums cache:

--------------------------------------------------------------------------------
Reductions of Nitroalkenes Using Zinc and Aluminum Amalgam
--------------------------------------------------------------------------------

Comptes Rendus 213: 304 ('41) - Translation by Labrat

Amongst the reduction methods used in organic chemistry, there are many
methods using Zn. The zinc is used, either in metal form, or associated
with other metal in the form of a couple: Zn-amalgam (BER 46: 1837 ('13),
Zn-Cu, Zn-Pd and Zn-Pt are described in the literature. The couple Zn-Ni
has not received attention by chemists.

The Zn-Ni couple is only active in the presence of base: ammonia or
hydroxide ions. We've used ammonia as base in most cases.

Preparation of the couple: One can obtain this easily by treating a
ammoniacal solution of a nickel salt, e.g. the sulfate, with powdered zinc.
The nickel is reduced and releases hydrogen, while the zinc is transformed
into the oxide, which dissolve slowly in the ammoniacal solution. In some
cases it's necessary to remove the ionised nickel, either because it'll
form an insoluble complex with the substance to be reduced, or because one
wants to replace the ammonia with sodium/potassium hydroxide.

We've realised the hydrogenation of several functional groups in this work:

Oximes, isonitrosoketones
-------------------------
The ketoximes are reduced to the corresponding primary amines.
Phenethylamine and amphetamine were obtained starting from
methylphenylketoxime and methylbenzylketoxime. The isonitrosoketones are
reduced to aminoalcohols. We cite the case wherein isonitrosoacetophenone
is reduced to beta-phenylethanolamine.

Nitriles
--------
Benzyl cyanide is reduced to phenethylamine.

Reductive amination of ketones
------------------------------

If a commercial solution of ammonia is used (with added alcohol to
solubilise the ketone), one obtains a moderate yield of the corresponding
amine. Cyclohexanone gives a 60-70% yield of cyclohexylamine.
Methylbenzylketone is transformed in the same way to phenylisopropylamine.

--------------------------------------------------------------------------------

Ann.Pharm.France 7: 733('49) - Translated by Labrat

2,3-dimethoxyphenethylamine
----------------------------
We've prepared this substance by direct reduction of the nitrostyrene with
zinc amalgam in hydrochloric acid. Water is added to 24 g of the
nitrostyrene until the total volume is 650 ml. Add 100 ml concentrate HCl
and 10 ml of a 5% solution of HgCl2. Add with vigorous stirring in small
portions 46 g powdered zinc, amalgamated with 33 ml 5% HgCl2 solution. With
every addition of Zn, 15 ml concentrated HCl is added. The temperature is
not allowed to rise over 35 C. After complete disappeared of the
nitrostyrene, one filters the unreacted zinc and concentrates the acidic
solution in vacuo. Add NaOH/H20 solution until the precipitated zinc
redissolves and extract several times with ether. The ethereal solutions
are washed and dried over Na2SO4. The ether is evaporated and the residue
is fractionated to give 60% amine.

--------------------------------------------------------------------------------

On the reductive amination of P2P, using MeNO2 as the source of methylamine:

Yakugaku Zasshi; 77; 1957; 310; Chem.Abstr.; 1957; 11278;

2-MeCH:CHC6H4OMe (52g) in 400ml AcOH treated portionwise with 200g. Pb3O4
stirred 1 hour at 40 degrees, the solution treated with a small amount of
H2O, AcOH removed in vacuo, the residue extracted with Et2O, the Et2O
residue with 500ml 20% H2SO4 refluxed 3 hrs, and the end product with EtO2
gave 24g 2-MeOC6H4CH2COMe (I), I (32.8g) in 19g MeNO2 and 100ml EtOH added
dropwise to 30g Al-Hg in 500ml EtOH, refluxed 2-3 hours, the Al(OH)3 and
EtOH removed, the residue acidified with HCl, washed with Et2O, made
alkaline with NaOH, and the end product extracted with Et2O gave 29g
2-MeOC6H4CH2CH(NHMe)Me.

--------------------------------------------------------------------------------

Excerpt from Monatsh. Chem. 79 (1948) pp72-77

Direct reduction of the nitro compound to the amine:

1g 2,3-dimethoxy-beta-nitrostyrene was dissolved in a mixture of 10ml HOAc,
10ml EtOH and 10ml H2O by gentle heating, and 2g fine Al turnings were added.
The reduction started after the addition of some HgCl2 and was completed by
heating on a warm water bath after standing for two hours at room temp.
Workup was done in an analogous manner to the oxime (apparently filtration,
solvent removal under vacuum and an acid-base extraction).
0.58g was obtained after distillation at 1mmHg, 80-110° air bath temperature.
From that 0.67g of the picrate was obtained.

--------------------------------------------------------------------------------

Posted on the Hive 980815 by Zorohustra

In this dream I dreamed that I tried Eleusis's "Proposed nitro -> amine
reduction for general use" (which can be found at Rhodium's outstanding
page, check it out!).

13g of GOOD phenyl-2-nitropropene was dissolved in 150ml Glacial Acetic
Acid in a 500ml 3-neck RB.

55g of tech. Zinc powder was "purified" as in Vogel's 5:Ed. (washing with
10% HCl, then dH2O, followed by acetone).

The dry and pure Zinc was slowly added to the nitropropene solution, while
stirring at 700rpm. When ~2/3 of the Zinc had been added the solution
turned "rust-red". When all the Zinc had been added the temperature was
80C.

The solution was still stirred at 700rpm, the goal was to heat it to 100C,
but it became 106C, at which point it boiled(?!). The solution was no
longer "rust-red", the Zinc was again gray and the solution appeared to be
light-pink/red (observed by stopping the stirring for a while).

The stirrer speed was increased to 1100rpm and the solution was held like
this for another 30min (total time ~45min). The solution is now light
yellow, with some colorless foam.

"Perhaps I have made P2P instead the chemist thought." (I think I've read
in March that it can be made with Zn/HOAc).

60ml 37% ACS hydrochloric acid is put into the additionfunnel and added
over perhaps 20min, no spectacular reaction at all. 1-2 hour later another
20ml hydrochloric acid is added, can't hurt I mean.
The solution is now near colorless, its decantated from unreacted Zinc, the
solution dumped into 1000ml cool dH2O, the Zinc washed with 100ml dH2O.

The solution was washed with 3*60+50ml DCM (500ml sep. funnel Wink

. Then
basified with NaOH solution until pH 10-11, then extracted with 3*70+50ml
DCM.

The solvent was removed by destillation, leaving VERY LITTLE of
"something", 15ml anhydrous acetone was added and 2-3 small drops of 98%
sulfuric acid, crystals percipitated. But we are talking about a yield in
the 100mg range… The chemist dumped it all out, being more of a curios
chemist then a desperate speedhead.

The washings was also stripped from solvent by destillation and then dumped
into a satured bisulfitesolution, but no crystals formed.

Hmm, IF this reaction can give an acceptable yield this is at least NOT the
way to get it, there is really not much to do then but to try with lower
temperature, but I am not motivated.

--------------------------------------------------------------------------------
Zn/Hg Nitrostyrene reduction

To suspension 1.5 g of 5-bromo-1,3-dimethoxy-omega-nitrostyrene in 20 ml of
aqueous MeOH (1:1) was added 4.5 g. HCl (d=1.19) and 0.3 ml 5% aqueous HgCl2
soln. Under stirring this was reduced with 5 g. of Zn dust, previosly amalgamated
with 0.3 ml 5% HgCl2 soln, adding Zn in portions at 30-35°C during 30 min. After
addition completing, the reaction mass was heated to 45-50C and kept at this
temp under stirring during 30 min. Unreacted Zn was removed, filtrate basified
with 10% NaOH untill all deposited Zn(OH)2 was dissolved. Base was extracted
with toluene (3x50 ml), solvent ditilled off in vacuo, and residue dissolved
in 10 ml CH3OH, and treated with saturated soln of picric acid - yield 2.0 g
picrate, 83%

Ref: Zh. Org. Khim 35, 720 (1965)

--------------------------------------------------------------------------------
Zorohustra:

I have earlier dreamt about several more traditional approaches of the old,
but still useful (I hope Wink

Clemmensen reduction of phenylnitropropens,
these dreams have all turned out fruitless. The following is a modification
and in this dream there was product, even thou the yield was low.

This is my dream:

60g Zinc powder was mixed with 5g HgCl2 and carefully stirred until
homogenous, about 100ml d water was added and then slowly 4ml of
concentrated hydrochloric acid was added, the temperature rose to about 50C
and the amalgamation was finished within 5 minutes. The water was removed
by filtration and the amalgam was washed with MeOH.

The amalgam was placed in a 1000ml 3-neck RB flask containing 140ml MeOH,
the mixture was magnetically stirred and 70ml of concentrated hydrochloric
acid was slowly added, the temperature rose to about 65C. A condenser was
fitted, as well as an addition funnel. The temperature of the amalgam/MeOH
mixture was held at 50C with external heating.

Meanwhile, 15g of really pure 1-phenyl-2-nitropropene and 200ml MeOH was
mixed, the solution heated until boiling, to solve the crystals.

The hot solution was added to the addition funnel and over just 15 minutes
the whole 200ml was introduced into the RB. The solution boiled hard and
the temperature rose to 70C, all while stirring at 1100rpm. The solution
was left boiling for another 2 hours.

The workup was quite a mess and in retrospect I can say that the best thing
to do, probably, is to make the solution basic with 10% NaOH solution,
filter, remove MeOH, extract whit DCM, skip back-extraction and let the
distillation be the only cleanup.

Anyhow, after distillation the yield of amphetamine freebase was ~4ml, that
was collected at 125C with aspirator "vacuum".

Tips how to increase the yield are very welcome, preferable from a
Clemmensen dreaming bee, the refs always claim 60-70% yield, but that is
just not my experience..

--------------------------------------------------------------------------------
Lone Ranger:

Can you use a two phase system to incrase yields? The use HCl/zinc amalgam
and a toluene layer can be helpful in preventing an immpossible to seperate
complex forming with the zinc. JACS, vol 58, 1438

--------------------------------------------------------------------------------
Osmium:

Basifying with strong NH3 avoids precipitation of Zn(OH2) in the workup.

--------------------------------------------------------------------------------
Dreamer:

Yesterday i had a dream, i tried to reduce P2NP (phenyl-2-nitropropene) to
amphetamine with amalganated Al. I amalganated 20gr of Al. To this 20gr Al
i added 0.1 mol P2NP in 150ml Tetrahydrofuran (YES, tetrahydrofuran with
his peroxides). The 150ml didn't cover the foil in the 1l Flask and i added
another 150ml Smile

. I putted the condensor on the flask and all was immersed
in ice cold water!! (very important) Then i added slowly, in 10ml steps
100ml of a solution of (100ml 31% HCl and 50ml H2O), i didn't have 25% HCl.

The reaction TE climbed to 50°. To keep up the generation of bubbles i
added after 45 min the last 50 ml of HCl slowly in 10ml steps. The whole
mixture colled down to 20° and i let stand everything over night. Next day
i made all very basic through slowly addition of 50% NaOH (~100ml). When i
saw that with the addition of NaOH generated other bubbles,so i let
everything stand again for 4h. Then i filtered the whole solution with a
Buchner funnel, which was quite tedious because the grey shit is plugging
(that should be "verstopfen" in english, http://www2.echo.lu/edic/ is a
really good page for someone, who didn't follow english lessons at school)
the filter paper. Well, after 2h all was filtered. I extracted with 3*75ml
with a mixture of Chloroform and DCM (because once i recovered DCM i poured
it to chloroform --> errors of a computerfreak, which is playing the
chemist), i washed with 500ml of 10% NaOH (maybe an error, if amphetamine
dissolves in diluted NaOH, a lot of the product could be loosed, is this
true ?) the solvents where recovered and a red oil was the result.

Now i made the sulfate salt instead of the HCl salt, because the sulfate is
not so soluble in water (1part in 8.8parts of H2O). I added 2ml of the oil
to 20ml of ether and a few drops of 96% H2SO4, i got amorphic crystals.

I tried with 20ml den. 90° ethanol, again only amorphic crystals, maybe to
many impurities, so one should distill the amphetamine freebase at 102°(13)
under vaccuum. I couldn't, because my vaccum setup exploded a week ago.

(while heating a mixture under vacuum i didn't realize, that the water trap
of my vacuum hose was damaged, so the pressure in the glass of my vacuum
distillation setup, which was not fixed, growed, pushed the glassware out
of the ground joints, ...,) So i poured the last ~10-12ml of red oil to the
amorphic crystals in a 30ml 90% den. ethanol. I added a little bit of 96%
H2SO4. I waited 1min and i got a dense red-white mass. Remembering
eleusis's acetone wash of mdma, i poured 100ml of acetone into the mass, a
lot of crystals separated out. Everything seemed ok, but when i tried to
add more acetone i mixed up the 95% H2SO4 with the acetone (same color of
the flask Sad

() and i poured 5ml of 96% H2SO4 in the Acetone, den. Ethanol
and Amphtamine Sulfate. There was a lot of fizzing and the crystals
disappear !???!!!

WHY ?WHY ?WHY ?

Does acetone react with conc. sulfuric acid or ethanol and did one of these
reaction byproducts destroy my amphetamine sulfate?

Recovering the other crystals from ether gave 1 gr of brown-white with
acteone washed crystals. I don't know how high the yield is, maybe around
50%.I am sure that i can improve this reduction, because i was really
imprecise.

When i used tetrahydrofuran there where two layers. Is it ok if there are
two layers with the P2NP in the organic layer, without an alcohol, that
dissolves P2NP even in the water layer? Would it raise the yield if i add
some Alcohol? Could it be that in such a reduction with amalganated Al the
solvent is reduced too (acetone, methyl ethyl ketone -->in denaturated
ethanol) and reduces the reduktion power of the reaktion?
It is impossible for me to get methanol and pure isopropylalcohol without
acetone (i can get tetrahydrofurane or ethyl ether like distilled water,
but so funny it sounds no mathanol and 1l pure isopropyl alcohol costs like
95% ethanol). Is there a possibility to eliminate all chemicals beside
methanol and ethanol, and what does denaturated 1°category mean?

If the TE of such a reduction is kept low, will this reduction work for
MD-P2NP and is it possible to make a sulfate salt of MDA with a low
solubity in water too?

--------------------------------------------------------------------------
Sunlight (01-21-99): Al/Hg and acetic acid reduction of 2,5-DMNS to 2C-H

Recently I was dreaming about to reduce 2,5 dimethoxy nitrostyrene to the
amine 2C-H with Al/Hg and acetic acid. I waited about 50-60 % but I got
only 35%. Yields are not good, but Shulgin reports 40% in 2C-B and 50% in
2C-H with LAH, so might be interesting to avoid buy/use LAH.

Proportions I use :
1 nitro (grams)
10 acetic acid (ml)
15 ethanol 96 (ml)
5 water (ml)

The reaction must be carried at about 60 C, becuase then the nitro is dissolved.
Some tips are:

- Put the HgCl2 in the reaction, then add the Al squares at a rate enough to
keep the temp around 60, and add till the orange colour disappear. About the
double weight of nitro will be enough, may be less.

- Filter before add NaOH solution, if not the great amount of sodium acetate
formed complicates filtration, even crystallize in the flasks. Filter and wash
the cake with water, and then add NaOH.

--------------------------------------------------------------------------------
Zn/Hg reduction of 3-Br-4,5-MD-NS to 3-Br-4,5-MD-PEA

53 g (0.22 mole) 3-Bromo-4,5-methylenedioxynitrostyrene and amalgamated
Zink (prepared from zinc powder (200g) and HgCl2 (20g)were suspened in EtOH 2 L).
Under vigorous stirring, conc HCl was added portionwise into the above mixture
until the yellow coloring of the reaction mixture disappeared. After the
decoloration was completed, the reaction mixture were further stirred for 30 min.
An excess Zn/Hg was filtered off; EtOH was removed in vacuum. Yield 32g (46.7%)

Tomitza et al, Chem Pharm Bull 16, 217-226 (1968)

--------------------------------------------------------------------------------
Dr Gonzo (04-14-99) - NaBH4 + Al/Hg reduction of 2,5-DMP2NP to 2,5-DMA

10g of 2,5-dimethoxy-beta-nitropropene was placed in a 300 ml beaker with
magnetic stirbar and 250 ml methanol, and stirred for a few minutes to dissolve
as much as possible. Sloooowly... 50 mg at a time... 2.2 g NaBH4 was dropped
into the sirring solution, with moderate effervescence with every addition.
Addition of all the NaBH4 took less than 30 minutes. After a little bit more
stirring, 50 ml 20% HCl was added SLOWLY - if there's any hydride left, it will
bubble vigorously. About 300 mg HgCl2 was added and allowed to dissolve (still
stirring) for a couple of minutes. Shredded kitchen aluminum foil was added,
around half a gram at a time, allowing the foil to react mostly away before the
next portion was added, in order to keep the reaction rate and temperature down.
Several grams of Al were used, and the reaction was declared finished when all
color was gone and when the chemist thought enough Al had been added. About 500
ml dH2O was added (in a new beaker), and then it was basified with 10% NaOH
until the sludge turned from solution -> gel -> granules. This was allowed to
settle, then the usual gut-wrenching Al/Hg workup was done, with multiple
dilutions, extractions, etc. When the final DCM extractions were vacuumed off,
5.5 ml of impure presumed 2,5-dimethoxyamphetamine freebase (not analyzed, just
hoped to be right) was left. Yield: approximately 60%. A drop of freebase
produced crystals with the usual ether/IPA/HCl system.

This reaction was also run on straight phenyl-beta-nitropropene, except in
absolute ethanol and not methanol. Use MeOH! EtOH yields are poor. Anyway, 16g
phenyl-beta-nitropropene was reduced to amphetamine freebase, which was then
crystallized with 93% H2SO4 in 99% IPA. Yield: 3.5-4g amphetamine sulfate.
Bioassaying the product thoroughly kicked the asses of the experimental
subjects, and also produced extreme euphoria, most likely due to the joy of
having completed a successful synthesis.

--------------------------------------------------------------------------------
Piglet

NH2OH.HCl is readily available from photography supply. And a better reduction
using the Zn/Ni couple has been posted by labrat. Claims to reduce imines to
amines (ketone in 80% methanol saturated with NH3 at about 60-70%, yields higher
from oxime, the side-product being hydroxylamine (boo hoo!), the freebase of
which is a solid. It's active as MDA. If you really want MDA, put it right back
into the next batch being reduced!

Search for Labrats post (it IS there, I just havn't got the time) and then here
are some details. (I use the sulphate).

NiSO4 + 6 NH3 --> Ni(NH3)6SO4
Zn + H2O --> ZnO + H2
ZnO + 4 NH3 --> Zn(NH3)4(OH)2

Pour off the NH3 solution, add your oxime in 80% v/v Methanol solution, add
3 moles of NaOH and slowly add the Zn in portions (if it overheats, cool under
running water) until it's all added, heat for 90 minutes, cool, filter (wash
filtrate into mother liquor). Neutralize, extract, remove solvent (yielding the
hydroxylamine as solid) or simply make salt as you see fit (IE a mix of MDA/MDOH).

2 NaOH + Zn -->Na2[ZnO2] + 2H

--------------------------------------------------------------------------------

Thats what you wanted right?
-AC

Bluechip · Tue Mar 01, 2005 2:31 pm

LoL

You guys are funny.
Thanks for the tip!
Just thought we should have this here,seeing as we have the other OTC steps.

IndoleAmine · Dreamreader Deluxe

I am still sceptical as to whether P2NPs can be reduced by Al/Hg (maybe the product is hydroxylamine rather than amine?).
Reason: The idea and first writeup came from dreamer, and all CTH dreams this guy posted are simply FAKE. Don't know why he decided to post fictional bullshit, but a lot of reagents were wasted when a direct CTH reduction of various P2NPs was attempted, so I concluded he would be rambling instead of giving true experimental reports...

But then again, it found its way into rhods archive (or was it removed due to being simply wrong?), and various bees at the old hive seemed to have had good results with this one.

Experiment is king.

i_a

Maya · Fri Mar 04, 2005 5:42 pm

I would view any and all procedures and writeups as suspicious or fake unless they can be sourced and verified back to the original published literature. Even published literature has been known to have some mistakes from time to time. If the proposed mechanism is a novel one, then it should first be tested and verified independantly before it spreads as possible mis-information

monkichi · Sat Mar 05, 2005 3:56 am

I recall a successful anhydrous reductive amination from somewhere. I'll have to chase this up. Most reports seem to come out of the Hyperlab, with such adventurers as Antoncho.

nubee · Master Archiver

piperonal -> 3,4-methylenedioxyphenylacetone
quoted from mdma chapter of pihkal http://www.erowid.org/library/books_online/pihkal/pihkal109.shtml

An alternate synthesis of 3,4-methylenedioxyphenylacetone starts originally from piperonal. A suspension of 32 g electrolytic iron in 140 mL glacial acetic acid was gradually warmed on the steam bath. When quite hot but not yet with any white salts apparent, there was added, a bit at a time, a solution of 10.0 g of 1-(3,4-methylenedioxyphenyl)-2-nitropropene in 75 mL acetic acid (see the synthesis of MDA for the preparation of this nitrostyrene intermediate from piperonal and nitroethane). This addition was conducted at a rate that permitted a vigorous reaction free from excessive frothing. The orange color of the reaction mixture became very reddish with the formation of white salts and a dark crust. After the addition was complete, the heating was continued for an additional 1.5 h during which time the body of the reaction mixture became quite white with the product appeared as a black oil climbing the sides of the beaker. This mixture was added to 2 L H2O, extracted with 3x100 mL CH2Cl2, and the pooled extracts washed with several portions of dilute NaOH. After the removal of the solvent under vacuum, the residue was distilled at reduced pressure (see above) to provide 8.0 g of 3,4-methylenedioxyphenylacetone as a pale yellow oil.

see the above link for the rest: (3,4-methylenedioxyphenylacetone ---> 3,4-methylenedioxy-N-methylamphetamine (MDMA))

So does ne1 know of any reviews/writeups of this method or have any comments on it ??

lusitania · Tue Apr 26, 2005 9:51 am

does anyone have the article for going from piperine to piperonal. I checked the link at rhodium and its down. Much thanks Smile

lusitania · Wed Apr 27, 2005 11:36 am

Bumblebee · Wed Apr 27, 2005 6:04 pm

Bump? after 1 day?? Laughing

i have an zipped version, i may send you, that contains the whole information.

From Rhods Site:

via KMnO4

piperic acid --> piperonal
KMnO4, alkali, 3°C
byproducts: piperonylic acid, racem. 2,3-dihydroxy-succinic acid, oxalic acid
[18], [03], [24]

via Br2 and NaOH

piperic acid Br2
--------->
tetrabromopiperic acid NaOH
--------->
piperonal

... piperic acid ... reacts quickly with Br2 in CCl4 without forming of HBr
to a compound with the molecular formula C12H10Br4O4 ... [07, page 877]

... piperic acid ... addition occured when bromine was added ...
tetrabromopiperic acid (C12H10Br4O4, mp 160-165°C) resulted when
bromine in carbon disulfide was the reagent. ...
hot sodium hydroxide converted the tetrabromo acid to piperonal ... [04]

nitrosation of piperine

... we have nitrosated piperine using HN02, NOCl and N2O4. the
compounds identified from the nitrosation of piperine are piperonal ... [05]

references

[03]
analen der chemie und pharmacie 1874 172: 134-167
"untersuchungen ueber die constitution des piperins und seiner
spaltproducte piperinsaeure und piperidin - vierte abhandlung"
rud fittig, w h mielck

[04]
leo marion, II. the pepper alkaloides, 1. piperine, p.168,
the alkaloids, chemistry and physiology, volume I,
academic press inc, publishers, new york, 1950

[05]
j agric food chem 1992 40(11): 2211-2215
"nitrosation of piperine using different nitrosating agents:
characterization and mutagenicity of the products"
narmada r shenoy, ahmed s u choughuley, tulsi k shetty, rathin k bhattacharya
abstract: piperine, an N,N-disubstituted amide possessing a methylenedioxy moiety,
is the main pungent principle of pepper, a spice consumed by people throughout the
world. on nitrosation the reaction mixture exhibits mutagenic activity toward salmonella
typhimurium strains. in the present work we have nitrosated piperine using nitrous acid
(HN02), nitrosyl chloride (NOCl), and dinitrogen tetraoxide (N2O4). the compounds
identified from the nitrosation of piperine are piperonal (PA), 6-nitropiperonal (NPA),
3,4-(methylenedioxy)cinnamaldehyde (MDCA),
1- [5-(1,3-benzodioxol-6-nitro-5-yl)-l-oxo-2(E) ,4(E)-pentadienyllpiperidine (MNAP),
1- [5-(1,3-benzodioxol-5-yl)-l-oxo-2-nitro-2(E),4(E)-pentadienyl] - piperidine (MNOP),
1- [5-(1,3-benzodioxol-6-nitro-5-yl)-l-oxo-2-nitro-2(E),4(E)-pentadienyllpiperidine (DNP),
and N-nitrosopiperidine (NPIP). the mutagenicity of the unfractionated nitrosated reaction
mixture (UPNM) and compounds NPA, MNAP, MNOP and DNP toward S. typhimurium
TA 98 and TA 100 strains was studied. compounds NPA and DNP and the unfractionated
reaction mixture were found to be mutagenic toward both the strains.

[07]
"lehrbuch der organischen chemie", 2.berichtigte auflage 1983
robert t morrison, robert n boyd; verlag chemie, weinheim; ISBN 3-527-25761-6

[18]
analen der chemie und pharmacie 1869 152: 25-58
"untersuchungen ueber die constitution des piperins und seiner
spaltproducte piperinsaeure und piperidin - erste abhandlung"
rud fittig, w h mielck

[24]
berichte der deutschen chemischen gesellschaft 1890 23: 2372-2377
"ueber die bildung von traubensaeure durch oxydation ungesaettigter saeuren"
o doebner