Aminolysis is Any Chemical Reaction in Which a Molecule is Split Into Two Parts by Reacting With a Molecule of Ammonia or an Amine

8/10/2019 Aminolysis is Any Chemical Reaction in Which a Molecule is Split Into Two Parts by Reacting With a Molecule of A

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Aminolysis is any chemical reaction in which a molecule is split into two parts by reacting witha molecule of ammonia or an amine .

An example of an aminolysis reaction is the replacement of a halogen in an alkyl group (R-X) byan amine (R'-NH 2) and the elimination of hydrogen halide (HX).

R-X + R'-NH 2 R -NH-R' + HX

Another common example is the reaction of a primary amine or secondary amine with acarboxylic acid or with a carboxylic acid derivative to form an amide . This reaction is widelyused, especially in the synthesis of peptides . On the simple addition of an amine to a carboxylicacid, a salt of the organic acid and base is obtained. To overcome this, the carboxylic acid firstneeds to be "activated". This is usually done by converting the acid into a more reactivederivative (i.e. anhydride , acid halide ) or by using a coupling agent . In some cases, hightemperatures (>200 C) can overcome salt formation by driving off water, without the need for"activation" of the carboxyl group. The downside to this simple reaction is that the compounds

may decompose at these elevated temperatures.

The carboxylic acid derivatives can be esters , anhydrides, acid halides or any other activatedspecies.

The choice of activated carboxyl group or coupling agent can be very important in peptidesynthesis, as using the wrong one can lead to racemization .

Sample paper:

Carboxylic acids derivatives are simply groupsof compounds that contain a carbonyl group butwith an

electronegative atom attached to thecarbon. The difference in the structure leads to amajor change inreactivity. The reactions of thesegroups of compounds involve nucleophilicsubstitution. Although thereare abundant kindsof carboxylic acid derivatives, the experimentonly focuses on the common ones: acidhalides,acid anhydrides, esters and amides.Carboxylic acids and their derivatives areusually seen inindustrial processes and mostbiological pathways. Esters can be seen as fatsand within the cellmembrane. Esters are alsopresent in pleasant smelling liquids that areresponsible with the fragrant odorof fruits andflowers. Amides are also present in animalprotein and also in industrial products suchasnylon. Acid chlorides and acid anhydrides areused in the synthesis of carboxylic derivatives.These arenot usually found in nature because of its high reactivity property.One property of carboxylic acids isthat theyare acidic. Because of these, carboxylic acids aremostly made to react with bases such as NaOH

toyield a water soluble metal carboxylates.Carboxylic acids and their derivatives reactwith nucleophileswhich yields a formation of alcohol. The initially formed intermediate productexpels one of itssubstituents which is originallybonded to the carbonyl carbon forming a newcarbonyl compound. Thereaction is callednucleophilic acyl substitution reaction.The procedure for acyl halides, acidanhydrides,esters and amides is hydrolysis. Hydrolysis issimply the reaction with water to yieldacarboxylic acid. Also for acetyl chloride isalcoholysis: Schotten-Bauman Reaction. It is thereaction with
http://en.wikipedia.org/wiki/Ammoniahttp://en.wikipedia.org/wiki/Ammoniahttp://en.wikipedia.org/wiki/Ammoniahttp://en.wikipedia.org/wiki/Aminehttp://en.wikipedia.org/wiki/Aminehttp://en.wikipedia.org/wiki/Aminehttp://en.wikipedia.org/wiki/Halogenhttp://en.wikipedia.org/wiki/Halogenhttp://en.wikipedia.org/wiki/Halogenhttp://en.wikipedia.org/wiki/Alkylhttp://en.wikipedia.org/wiki/Alkylhttp://en.wikipedia.org/wiki/Alkylhttp://en.wikipedia.org/wiki/Carboxylic_acidhttp://en.wikipedia.org/wiki/Carboxylic_acidhttp://en.wikipedia.org/wiki/Amidehttp://en.wikipedia.org/wiki/Amidehttp://en.wikipedia.org/wiki/Amidehttp://en.wikipedia.org/wiki/Peptidehttp://en.wikipedia.org/wiki/Peptidehttp://en.wikipedia.org/wiki/Peptidehttp://en.wikipedia.org/wiki/Anhydridehttp://en.wikipedia.org/wiki/Anhydridehttp://en.wikipedia.org/wiki/Anhydridehttp://en.wikipedia.org/wiki/Acid_halidehttp://en.wikipedia.org/wiki/Acid_halidehttp://en.wikipedia.org/wiki/Acid_halidehttp://en.wikipedia.org/w/index.php?title=Coupling_agent&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=Coupling_agent&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=Coupling_agent&action=edit&redlink=1http://en.wikipedia.org/wiki/Esterhttp://en.wikipedia.org/wiki/Esterhttp://en.wikipedia.org/wiki/Esterhttp://en.wikipedia.org/wiki/Racemizationhttp://en.wikipedia.org/wiki/Racemizationhttp://en.wikipedia.org/wiki/Racemizationhttp://en.wikipedia.org/wiki/Racemizationhttp://en.wikipedia.org/wiki/Esterhttp://en.wikipedia.org/w/index.php?title=Coupling_agent&action=edit&redlink=1http://en.wikipedia.org/wiki/Acid_halidehttp://en.wikipedia.org/wiki/Anhydridehttp://en.wikipedia.org/wiki/Peptidehttp://en.wikipedia.org/wiki/Amidehttp://en.wikipedia.org/wiki/Carboxylic_acidhttp://en.wikipedia.org/wiki/Alkylhttp://en.wikipedia.org/wiki/Halogenhttp://en.wikipedia.org/wiki/Aminehttp://en.wikipedia.org/wiki/Ammonia


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an alcohol to yield an ester. Thealcohol used here was ethanol. Again for acetylchloride and acetic

anhydride, the...

Sample paper:

Carboxylic acid derivatives are organic compounds containing the acyl group core structure attached toa Y group, which may be an electronegative atom or substituent. The Y group acts as a leaving group innucleophilic acyl substitution. This mechanism is involved in hydrolysis, alcoholysis, and aminolysisreactions.

As strong organic acids, carboxylic acids react with silver nitrate and sodium bicarbonate to form thecorresponding carboxylate salts.

Among the carboxylic acid derivatives, acyl halides are the most reactive and amides the least. Thus, thereactions of these compounds with a given reagent vary with regard to the rate, thermochemistry, andeven the completion of the reaction.

Acyl chlorides, due to their reactivity, are good starting materials for synthesis. Esters and amides areimportant functional groups in biomolecules like fats and proteins.

All carboxylic acid derivatives yield the parent carboxylic acid upon reaction with water. Moreover, one

derivative can be converted into another, provided the former is more reactive than the latter.

My citations:

Ouellette,R.J., (1994). Organic Chemistry: a brief introduction . 1st ed. New York,New York:Macmillan Publishing Company.

Brown,W.H.,Foote,C.S., (2002). Organic Chemistry . 3rd ed. Florida: Harcourt CollegePublisher.

Lehman,J.W., (2002). Multiscale Operational Organic Chemistry . 1st ed. Saddle River,NewJersey: Prentice Hall.

Pavia,D.L.,Lampman,G.M.,Kriz,G.S., (1999). Organic Laboratory Techniques: A microscaleapproach . 3rd ed. : Brooks/Cole Publishing Company.

Landgrebe,J.A., (1982). Theory and Practice In the Organic Laboratory: microscale and standard scale experiments . 4th ed. Pacific Grove,California: Brooks/Cole Publishing Company.

Brown,W.H.,Poon,T., (2014). Introduction to Organic Chemistry . 5th ed. Hoboken,New Jersey:John Wiley & Sons,Inc..

Aminolysis:


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Acid chlorides react with water to yield carboxylic acids

HCl is generated during the hydrolysis: a base is added to remove the HCl


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anhydride preparations were not general and required strong heating. A better and more generalanhydride synthesis can be achieved from acyl chlorides, and amides are easily made from anyof the more reactive derivatives. Specific examples of these conversions will be displayed byclicking on the product formula. The carboxylic acids themselves are not an essential part of thisdiagram, although all the derivatives shown can be hydrolyzed to the carboxylic acid state (light

blue formulas and reaction arrows). Base catalyzed hydrolysis produces carboxylate salts.

Before proceeding further, it is important to review the general mechanism by means of whichall these acyl transfer or acylation reactions take place. Indeed, an alert reader may well be puzzled by the facility of these nucleophilic substitution reactions. After all, it was previouslynoted that halogens bonded to sp 2 or sp hybridized carbon atoms do not usually undergosubstitution reactions with nucleophilic reagents. Furthermore, such substitution reactions ofalcohols and ethers are rare, except in the presence of strong mineral acids. Clearly, themechanism by which acylation reactions occur must be different from the S N1 and S N2

procedures described earlier.In any substitution reaction two things must happen. The bond from the substrate to the leavinggroup must be broken, and a bond to the replacement group must be formed. The timing of theseevents may vary with the reacting system. In nucleophilic substitution reactions of alkyl

compounds examples of bond-breaking preceding bond-making (the S N1 mechanism ), and of bond-breaking and bond-making occurring simultaneously (the S N2 mechanism ) were observed.On the other hand, for most cases of electrophilic aromatic substitution bond-making preceded

bond-breaking.

As illustrated in the following diagram, acylation reactions generally take place by an addition-elimination process in which a nucleophilic reactant bonds to the electrophilic carbonyl carbonatom to create a tetrahedral intermediate. This tetrahedral intermediate then undergoes an
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elimination to yield the products. In this two-stage mechanism bond formation occurs before bond cleavage, and the carbonyl carbon atom undergoes a hybridization change from sp 2 to sp 3 and back again. The facility with which nucleophilic reagents add to a carbonyl group was notedearlier for aldehydes and ketones .

Acid and base-catalyzed variations of this mechanism will be displayed in turn as the"Mechanism Toggle" button is clicked. Also, a specific example of acyl chloride formation fromthe reaction of a carboxylic acid with thionyl chloride will be shown. The number of individualsteps in these mechanisms vary, but the essential characteristic of the overall transformation isthat of addition followed by elimination . Acid catalysts act to increase the electrophilicity ofthe acyl reactant; whereas, base catalysts act on the nucleophilic reactant to increase itsreactivity. In principle all steps are reversible, but in practice many reactions of this kind areirreversible unless changes in the reactants and conditions are made. The acid-catalyzedformation of esters from carboxylic acids and alcohols, described earlier , is a good example of areversible acylation reaction, the products being determined by the addition or removal of waterfrom the system. The reaction of an acyl chloride with an alcohol also gives an ester, but thisconversion cannot be reversed by adding HCl to the reaction mixture.

Mechanisms of Ester Cleavage

Esters are one of the most common carboxylic derivatives. Cleavage of the alkyl moiety in an ester may be effectedin several different ways, the most common being the acyl transfer mechanism described above; however, othermechanisms have been observed. For examples and further discussion Click Here .
https://www2.chemistry.msu.edu/faculty/reusch/virttxtjml/aldket1.htm#prophttps://www2.chemistry.msu.edu/faculty/reusch/virttxtjml/aldket1.htm#prophttps://www2.chemistry.msu.edu/faculty/reusch/virttxtjml/aldket1.htm#prophttps://www2.chemistry.msu.edu/faculty/reusch/virttxtjml/crbacid1.htm#crbacd6chttps://www2.chemistry.msu.edu/faculty/reusch/virttxtjml/crbacid1.htm#crbacd6chttps://www2.chemistry.msu.edu/faculty/reusch/virttxtjml/crbacid1.htm#crbacd6chttps://www2.chemistry.msu.edu/faculty/reusch/virttxtjml/suppmnt4.htm#top1https://www2.chemistry.msu.edu/faculty/reusch/virttxtjml/suppmnt4.htm#top1https://www2.chemistry.msu.edu/faculty/reusch/virttxtjml/suppmnt4.htm#top1https://www2.chemistry.msu.edu/faculty/reusch/virttxtjml/suppmnt4.htm#top1https://www2.chemistry.msu.edu/faculty/reusch/virttxtjml/crbacid1.htm#crbacd6chttps://www2.chemistry.msu.edu/faculty/reusch/virttxtjml/aldket1.htm#prop


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Thus far we have not explained the marked variation,noted above , in the reactivity of different carboxylicacid derivatives. The distinguishing carbonylsubstituents in these compounds are: chloro (acylchlorides), acyloxy (anhydrides), alkoxy (esters) and

amino (amides). All of these substituents have bondsoriginating from atoms of relatively highelectronegativity (Cl, O & N). They are thereforeinductively electron withdrawing when bonded to carbon, as shown in the diagram on the right.The consequences of such inductive electron withdrawal on the acidity of carboxylic acids was

previously noted . When these substituents are attached to an sp 2 carbon that is part of a -electron system, a similarinductive effect occurs, but n- conjugation (p - conjugation) moves electron density in theopposite direction. By clicking the "Toggle Effect" button the electron shift in both effects will

be displayed sequentially. This competition between inductive electron withdrawal andconjugative electron donation was discussed earlier in the context of substituent effects on

electrophilic aromatic substitution . Here, it was noted that amino groups were strongly electrondonating (resonance effect >> inductive effect), alkoxy groups were slightly less activating,acyloxy groups still less activating (resonance effect > inductive effect) and chlorine wasdeactivating (inductive effect > resonance effect). In the illustration on the right, R and Zrepresent the remainder of a benzene ring.This analysis also predicts the influence these substituent groups have on the reactivity ofcarboxylic acid derivatives toward nucleophiles (Z = O in the illustration). Inductive electronwithdrawal by Y increases the electrophilic character of the carbonyl carbon, and increases itsreactivity toward nucleophiles. Thus, acyl chlorides (Y = Cl) are the most reactive of thederivatives. Resonance electron donation by Y decreases the electrophilic character of thecarbonyl carbon. The strongest resonance effect occurs in amides, which exhibit substantialcarbon-nitrogen double bond character and are the least reactive of the derivatives. Aninteresting exception to the low reactivity of amides is found in beta-lactams such as penicillinG. The angle strain introduced by the four-membered ring reduces the importance of resonance,the non-bonding electron pair remaining localized on the pyramidally shaped nitrogen. Finally,anhydrides and esters have intermediate reactivities, with anhydrides being more reactive thanesters.

Alcoholysis of acyl chlorides and acid anhydrides

Alcohols react with acyl chlorides and acid anhydrides to give esters:

RCOCl + R'OH RCO 2R' + HCl

(RCO) 2O + R'OH RCO 2R' + RCO 2H

The reactions are irreversible simplifying work-up . Since acyl chlorides and acid anhydrides alsoreact with water, anhydrous conditions are preferred. The analogous acylations of amines to giveamides are less sensitive because amines are stronger nucleophiles and react more rapidly thandoes water. This method is employed only for laboratory-scale procedures, as it is expensive.
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Documents

Aminolysis is Any Chemical Reaction in Which a Molecule is Split Into Two Parts by Reacting With a Molecule of Ammonia or an Amine