docberto
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Amine electrophiles
Does anyone know anything about the use of amines as electrophiles? I don't mean nitronium or nitrosyl cations. Is the nitrogen in chloramines
and hydroxylamines electrophilic? I was thinking that this could be a good method for amine addition to compounds. Perhaps an aromatic could be
aminated with hydroxylamine and concentrated H2SO4. Or a carbon nucleophile could attack N-chlorophthalimide in a backwards Gabriel amine synthesis.
I may get around to attempting the amination of toluene.
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mykhal
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Electrophilic amination
In my opinion, it is not possible to perform amine umpolung by substitution, because it will still contain en electron pair and no vacant orbital on N
atom. However, some examples of electrophilic amination (try googling it) have been done using various reagents. For example, aniline can be prepared
from benzene directly in excellent yield using trimethylsilyl azide and trifluoroacetic acid (Olah A., Ernst D.: J. Org. Chem
1989, 54, 1203-1204.)
NOTE: Hydroxylamine should be more nucleophilic (!) than amines due to alpha effect (neighbouring atom carrying lone electron pair
increases nucleophilicity). But sometimes, somewhere, I have seen one example of aromatic amination using hydroxylamine in acidic conditions (probably
-OH protonation -> water leaving group). Just try it. :)
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Natures Natrium
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Vogels has a preparation which might interest you.
IV,38. p-NAPHTHYLAMINE
Pass a stream of sulphur dioxide into 200 ml. of cooled, concentrated
ammonia solution (sp. gr. 0*88) until 50 g. of gas have been absorbed.
Place this ammonium sulphite solution together with 72 g. of (3-naphthol
(Section IV,102) in an autoclave (see Section VI,4) provided with a
stirrer or shaking mechanism. Securely fasten the cap and heat at
150° with continual shaking or stirring for 8 hours : allow to cool with
shaking or stirring. Remove the reaction mixture from the apparatus
with the aid of about 250 ml. of water. Filter on a Buchner funnel.
Dissolve the crude material in a boiling mixture of 75 ml. of concentrated
hydrochloric acid and 200 ml. of water, and then dilute with 500 ml. of
water. Add 5 g. of decolourising carbon, boil for 5 minutes, and filter
through a hot water funnel from any undissolved dinaphthylamine
(C10H7NHC10H7). Pour the hot filtrate with stirring into a solution of
60 g. of sodium hydroxide in 250 ml. of water. Make sure that the
resulting slurry is alkaline to phenolphthalein; cool it with stirring to
20°, filter with suction, and wash with 1 litre of cold water. Press well.
Dry the product to constant weight at 50-60°. The yield of (3-naphtnylamine,
m.p. 111-112°, isolated as a light tan powder, is 68 g.
CAUTION. This compound has carcinogenic properties and great care
should be taken to avoid all contact with it during its isolation and drying.
You would need an autoclave though. 
\"The man who does not read good books has no advantage over the man who cannot read them.\" - Mark Twain (1835-1910)
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Kinetic
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Electrophilic amines
Actually, it is possible to use haloamines as electrophiles. However, I really cannot see any advantage to doing so as the traditional methods, even
though they generally involve a two-step method - such as introduction of an electrophilic nitrogen species followed by reduction - are usually
better. The example I use to justify this is the preparation of a family of 'alpha-alkylaminoacylophenones', the most notorious of these
being methcathinone. Patent US2155194 details the use of N-alkyl-N-bromoamines that react as electrophiles in the presence of nucleophilic ketones such as
propiophenone to give the aminoketones directly. I don't think arenes would be nucleophilic enough to make this viable for the synthesis of
anilines. I see no advantage to this patented modification when compared to the usual route: that is, addition of bromine to propiophenone to give the
electrophilic bromoketone, followed by addition of the nucleophilic amine. This route, in my opinion, is more practical than the method outlined in
the patent.
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Nicodem
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There are only a few cases of direct ammination of the aromatic compounds with "unpoolung-ed amines". Here are the two pages from
Saul Patai. The chemistry of the amino group. Interscience publishers, 1968.
dealing with this reactions. The front page of the book and the reference pages are added. I hope this helps.
Attachment: direct_ammination.pdf (99kB)
This file has been downloaded 1483 times
…there is a human touch of the cultist “believer” in every theorist that he must struggle against as being
unworthy of the scientist. Some of the greatest men of science have publicly repudiated a theory which earlier they hotly defended. In this lies their
scientific temper, not in the scientific defense of the theory. - Weston La Barre (Ghost Dance, 1972)
Read the The ScienceMadness Guidelines!
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docberto
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Kinetic, coincidentally, this question began out of a speculative synthesis of a cathinone from a propiphenone. So perhaps this would be a productive
avenue to pursue. Maybe better than the brominate, then aminate approach.
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Kinetic
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Cathinones
Perhaps, but I doubt it. There is certainly no advantage when it comes to cutting out steps, as although not having to brominate the ketone saves a
step, the preparation of the bromoamine adds one.
There were several quite detailed threads on cathinones from propiopheones on the Hive, but I can only find one of them. I have plenty of experience
making cathinone analogues from propiophenones/butyrophenone, and I believe that the essentially one-pot addition of bromine to the ketone, followed
by addition of the alkylamine will be a better route both yield-wise and for its simplicity. The only one I can find is my Benzene -> Methaephetamine thread. Obviously you would only follow the first two steps if you were interested in the cathinone
analogue/homologue. The workup of the second step would also have to be modified to give the cathinone as the HCl salt instead of the freebase (this
was detailed in another thread, but if you're interested I can provide details).
Are you interested in any particular cathinone analogue?
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Sandmeyer
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What follows is a communication, which is also a mini-review on the usage of amine electrophiles for amination.
http://rapidshare.de/files/7769911/Copper-Catalyzed_Electrop...
Copper-Catalyzed Electrophilic Amination of Diorganozinc Reagents
Berman, A. M.; Johnson, J. S.;
J. Am. Chem. Soc.; (Communication); 2004; 126(18); 5680-5681. DOI: 10.1021/ja049474e
[Edited on 17-11-2005 by Sandmeyer]
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mert
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it has been delete
Could u again upload it, please? a lot thanks
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Sandmeyer
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ok, here you go...
Main article: http://rapidshare.de/files/28327959/main.pdf.html
Supporting Info:
http://rapidshare.de/files/28328044/support.pdf.html
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mert
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Sandmeyer, a lot thanks 
this article is very important for me alot thanks
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A_K_190
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hi every body i'm new here and i want to be ur friend
and i have a question
how can i synthesize indol by Fischer method i want a full procedure plz 
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Nicodem
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There is no method to prepare indole itself by using the Fischer cyclisation.
Utmost it is possible to prepare indole-2-caboxylic acid with the Fischer cyclisation of pyruvic acid phenylhydrazone. Indole-2-caboxylic acid can
then be decarboxylated to indole.
PS: And if you want us to be "ur friend" I suggest you use proper capitalization and spelling.
…there is a human touch of the cultist “believer” in every theorist that he must struggle against as being
unworthy of the scientist. Some of the greatest men of science have publicly repudiated a theory which earlier they hotly defended. In this lies their
scientific temper, not in the scientific defense of the theory. - Weston La Barre (Ghost Dance, 1972)
Read the The ScienceMadness Guidelines!
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A_K_190
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sorry if i misstyped it but i want really to be one of this group
and for the indole i can synthesis 2-methylindol by this method by
phenylhydrazine+acetone------------> by heat and prescence of sulfuric acid i think i can obtain it but i want to know the procedure / steps and
quantities
and thank u very much
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Nicodem
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Please be more specific. What exactly is it that you want to prepare, indole or 2-methylindole?
If it is 2-methylindole that you want then there is one procedure in Organic Syntheses, Coll. Vol. 3, p.597 (1955); Vol. 22, p.94 (1942). There you will also find three references for the preparation using the
acetone phenylhydrazone in a Fischer cyclisation with ZnCl2 as acid catalyst.
…there is a human touch of the cultist “believer” in every theorist that he must struggle against as being
unworthy of the scientist. Some of the greatest men of science have publicly repudiated a theory which earlier they hotly defended. In this lies their
scientific temper, not in the scientific defense of the theory. - Weston La Barre (Ghost Dance, 1972)
Read the The ScienceMadness Guidelines!
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A_K_190
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thanks for help and i'm not a scientist i'm just an amateur who loves organic
synthesis and i've simple chemicals which i love to use to synthesis new compounds but working with no procedure is a catastrophe,isn't it? so i'm
here to find some help
and for that equation "phenylhydrazine+acetone------------> by heat and prescence of sulfuric acid------>2-methylindole"
depending on a 3,3'-sigmatropic rearrangement does it work ??
and if it works,what are the quntities and procedure??
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Nicodem
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I only saw Fischer syntheses of 2-metylindole using ZnCl2 as acid, for which I already gave you three references with the preparative procedure. I'm
not saying there is no reference using H2SO4 as acid, just that I have not seen it yet, but haven't searched either.
PS: Most people on this forum are not scientists either, just mad scientists which is something completely different.
…there is a human touch of the cultist “believer” in every theorist that he must struggle against as being
unworthy of the scientist. Some of the greatest men of science have publicly repudiated a theory which earlier they hotly defended. In this lies their
scientific temper, not in the scientific defense of the theory. - Weston La Barre (Ghost Dance, 1972)
Read the The ScienceMadness Guidelines!
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A_K_190
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mad scientists ohhh!!!! so GOD save the world then i've found my future
friends
the link u gave me is explaining a completely diffrent method not what i meant and i couldnot find the method i desire
and if possible would u give me links for sites that give procedures so that i can find a refrence for my future synthesis projects
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Nicodem
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Read that Org. Synth. paper more thoroughly, especially the “3.Discussion” paragraph. I already told you there are 3 references there for the
Fischer synthesis of 2-methylindole using acetone phenylhydrazone with zinc chloride at 180°. Should I explicitly point and cite them to you?
Procedures for organic syntheses can generally be found by using references. References point to scientific literature. Scientific literature can
generally be found in libraries or if you have access, from the publisher. All this up to here can be done without you being a scientist. All it
really takes is to go to the library. You might also be lucky and get the paper online from one of the freely accessible journals. Alternatively, if you are more of a lazy kind of person, you can ask others to provide you papers (that’s what the
"References" forum is for!). Then you need to read, read and read more.
But in reality things are much, much more complicated.
For example, you might ask yourself how to search for the references. It is a big problem indeed. You need access to some distant place where two of
the greatest magicians live. They are called Herr Beilstein and Sir SciFinder. Now these two great magicians
generally don’t allow you near unless you prove to be worthy of their attention or unless you have The Money to bribe them. So you
are left with the many lesser magicians, better known as The Search Engines, who operate trough magic spells only. These spells are
also known as The Keywords. These magicians live very near the source of all scientific knowledge, the books of magic, also known as
The Journals. Lesser magicians will only give you the references in their possession if you type in the right keywords but unlike
Herr Beilstein and Sir SciFinder they will not allow you to use the magic runes of chemistry, the so called Structures. Now, each of
these lesser magicians only has as much references as their masters allow them to have. These masters are very important monster creatures and are
generaly known as The Publishers. The masters will only allow you to ask the magicians for the references but will not allow you to
take any precious scripture from The Journals unless you can pay with gold. These scriptures are contained in the books of The Journals and are often
called simply Papers. You can find the covens of these Publishers with their lesser magicians inside the network of the magic
universal mastermind, also known as The Internet.
Well, in short use these links to the publisher's covens:
ACS, RSC, Scirus, Elsevier, Thieme, Wiley...
Another trick to contact one of the lesser magicians that will temporarily allow you to use even the magic of The Structures is to get the free demo
account at Spresi.
There is actually an even much, much easier trick if you are a poor and defenseless wanabee chemist without the slightest magical skill. You can just
ask others to search the references for you. Oh, but you already know that.
I hope you now understand what the difference between science and mad science is. A scientist has all the references and tools he needs, but a mad
scientist has to use magic.
…there is a human touch of the cultist “believer” in every theorist that he must struggle against as being
unworthy of the scientist. Some of the greatest men of science have publicly repudiated a theory which earlier they hotly defended. In this lies their
scientific temper, not in the scientific defense of the theory. - Weston La Barre (Ghost Dance, 1972)
Read the The ScienceMadness Guidelines!
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Nicodem
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A_K_190, I forgot to mention two other very elementary but quite important methods for reference hunting:
Method 1: This is the so called “spidering for references” (I just invented this phrase for the sake of giving it a name). This consist in
taking one paper that is at least somehow relevant to your subject (how you find this paper is up to you). Then you read it and check all the
references found in that paper having somewhat more relevance to your subject than this first paper itself. Then you go to the library and check out
those papers indicated by the checked references. You then repeat the process from the beginning untill you find the most relevant reference to
whatever you want to achieve. If you are lucky you can hunt down some pertinent review paper which is by definition very rich in references.
Method 2: The other method is searching for books that are somehow connected to your subject. Books can be considered as some large review paper
and are rich in references (as long as they are not school books, which by definition avoid using references otherwise students would have easy access
to knowledge and teachers would be unemployed). With some luck you can find a useful reference in such books. If the reference is not as useful as you
would want it to be, you can still continue with the method 1 until you find a better one.
Now these two methods are terribly time consuming and less effective than asking Herr Beilstein, Sir SciFinder or Lord Gmelin (this last one that you
still don’t know is the great magician that inorganic chemist use to consult). But at least, these methods can be used by anybody, including
you.
| Quote: | Originally posted by Nicodem
There is no method to prepare indole itself by using the Fischer cyclisation. |
Now, here I have to correct myself. Using the above mentioned Method 2 for
reference hunting I realized that there actually exists a way to make indole from acetaldehyde phenylhydrazone. But it is done by a modification of
the Fischer cyclization, that is in vapor phase over Al203, MgO, MgO/SiO2 catalysts (ref 1) or Al203/MgF2 catalyst (ref 2). Clearly it is not
something one could easily do in a garage lab, but here are the two references:
[1] Suvorov, N. N.; Shkil'kova, V. N.; Podkhalyuzina, N. Ya. Chem. Heterocycl. Cmpds., Eng. Transl. 24, 1191 (1988).
[2] Esteban, S.; Marinas, J. M.; Martinez-Alcazar, M. P.; Martinez, M.; Agarabeitia, A R. Bull. Soc. Chim. Belg. 92, 715
(1983).
PS: There actually exists a book dedicated to the Fischer Indole Synthesis only:
B. Robinson. The Fischer Indole Synthesis (John Wiley and Sons, New York, 1982).
…there is a human touch of the cultist “believer” in every theorist that he must struggle against as being
unworthy of the scientist. Some of the greatest men of science have publicly repudiated a theory which earlier they hotly defended. In this lies their
scientific temper, not in the scientific defense of the theory. - Weston La Barre (Ghost Dance, 1972)
Read the The ScienceMadness Guidelines!
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A_K_190
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thanks for good explanation of items i wasnot really understand and i think i'll go to my college library for my search and now i understood what u
mean by mad scientists
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unome
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There is also the reportedly facile decarboxylation of ethyl indole-2-carboxylate as mentioned in this abstract, I have that paper if anyone wants it, 4-nitroindole interests a few people apparently
NB It uses the various nitrophenylhydrazones of ethyl pyruvate, unsubstituted anilines are unknown quantities, but someone here should know
[Edited on 30-10-2009 by unome]
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