amide hydrolysis

AMIDE

Amida is a type of chemical that can have two senses. The first type is an organic functional group having a carbonyl group (C = O), which binds to a nitrogen atom (N), or a compound that contains this functional group. The second kind is a form of nitrogen anion.

Amine is a nitrogen-containing organic compounds with a partner elektronbebas. tururnan of the amine is ammonia, which is where one or more alkyl groups replaced by hidrogennyatelah. many amine compounds are very pentingdalam life as Amino Acids, aniline, and triethylamine.
Amide is an organic compound with the acyl group (RC = O) connected denganAtom Nitrogen. Amide is also often referred to as compounds derived from Amoniamaupun Amina. The simplest amide is a derivative of ammonia in it is replaced by hydrogen dengansatu acyl group.

Interconversion Reactions of Amides

Reaction type:  Nucleophilic Acyl Substitution

Summary

• Amides are the least reactive of the neutral carboxylic acid derivatives.
• The only interconversion reaction that amides undergo is hydrolysis back to the parent carboxylic acid and the amine.
• Reagents : Strong acid (e.g. H₂SO₄) or strong base (e.g. NaOH) / heat.
• More details on the following page.

Hydrolysis of Amides

Reaction type:  Nucleophilic Acyl Substitution

Summary

• Amides hydrolyze to the parent carboxylic acid and the appropriate amine.
• The mechanisms are similar to those of esters.
• Reagents : Strong acid (e.g. H₂SO₄) / heat (preferred) or strong base (e.g. NaOH) / heat.

Related Reactions

Hydrolysis of Esters

Reaction under ACIDIC conditions:

• Note that the acid catalyzed mechanism is analogous to the acid catalyzed hydrolysis of esters.
• The mechanism shown below proceeds via protonation of the carbonyl not the amide N (see step 1).
• The mechanism is an example of the less reactive system type.

MECHANISM OF THE ACID catalyzed  HYDROLYSIS OF AMIDES
Step 1: An acid/base reaction. Since we only have a weak nucleophile and a poor electrophile we need to activate the ester. Protonation of the amide carbonyl makes it more electrophilic.
Step 2: The water O functions as the nucleophile attacking the electrophilic C in the C=O, with the electrons moving towards the oxonium ion, creating the tetrahedral intermediate.
Step 3: An acid/base reaction. Deprotonate the oxygen that came from the water molecule.
Step 4: An acid/base reaction. Need to make the -NH2 leave, but need to convert it into a good leaving group first by protonation.
Step 5: Use the electrons of an adjacent oxygen to help "push out" the leaving group, a neutral ammonia molecule.
Step 6: An acid/base reaction. Deprotonation of the oxonium ion reveals the carbonyl in the carboxylic acid product and regenerates the acid catalyst.

Reduction of Amides
(for more detail see Chapter 22)

Reactions usually in Et₂O or THF followed by H₃O⁺ work-ups

Reaction type:  Nucleophilic Acyl Substitution then Nucleophilic Addition

Summary

• Amides, RCONR'₂, can be reduced to the amine, RCH₂NR'₂ by conversion of the C=O to -CH₂-
• Amides can be reduced by LiAlH₄ but NOT the less reactive  NaBH₄
• Typical reagents :  LiAlH₄  / ether solvent followed by aqueous work-up.
• Note that this reaction is different to that of other C=O compounds which reduce to alcohols
• The nature of the amine obtained depends on the substituents present on the original amide.
  look at the N substituents in the following examples (those bonds don't change !)

• R, R' or R" may be either alkyl or aryl substituents.
• In the potential mechanism note that it is an O system that leaves. This is consistent with O systems being better leaving groups that the less electronegative N systems.

REACTION OF LiAlH4 WITH AN AMIDE
Step 1: The nucleophilic H from the hydride reagent adds to the electrophilic C in the polar carbonyl group of the ester. Electrons from the C=O move to the electronegative O creating an intermediate metal alkoxide complex.
Step 2: The tetrahedral intermediate collapses and displaces the O as part of a metal alkoxide leaving group, this produces a highly reactive iminium ion an intermediate.
Step 3:   Rapid reduction by the nucleophilic H from the hydride reagent as it adds to the electrophilic C in the iminium system. p electrons from the C=N move to the cationic N neutralizing the charge creating the amine product. AMIDE USEFULNESS IN LIFE Nylons are condensation copolymers formed by reacting equal parts of a diamine and a dicarboxylic acid, so that amides are formed at both ends of each monomer in a process analogous to polypeptide biopolymers. Chemical elements included are carbon, hydrogen, nitrogen, and oxygen. The numerical suffix specifies the numbers of carbons donated by the monomers; the diamine first and the diacid second. The most common variant is nylon 6-6 which refers to the fact that the diamine (hexamethylene diamine, IUPAC name: hexane-1,6-diamine) and the diacid (adipic acid, IUPAC name: hexanedioic acid) each donate 6 carbons to the polymer chain. As with other regular copolymers like polyesters and polyurethanes, the "repeating unit" consists of one of each monomer, so that they alternate in the chain. Since each monomer in this copolymer has the same reactive group on both ends, the direction of the amide bond reverses between each monomer, unlike natural polyamide proteins which have overall directionality: C terminal → N terminal. In the laboratory, nylon 6-6 can also be made using adipoyl chloride instead of adipic. It is difficult to get the proportions exactly correct, and deviations can lead to chain termination at molecular weights less than a desirable 10,000 daltons (u). To overcome this problem, a crystalline, solid "nylon salt" can be formed at room temperature, using an exact 1:1 ratio of the acid and the base to neutralize each other. Heated to 285 °C (545 °F), the salt reacts to form nylon polymer. Above 20,000 daltons, it is impossible to spin the chains into yarn, so to combat this, some acetic acid is added to react with a free amine end group during polymer elongation to limit the molecular weight. In practice, and especially for 6,6, the monomers are often combined in a water solution. The water used to make the solution is evaporated under controlled conditions, and the increasing concentration of "salt" is polymerized to the final molecular weight. DuPont patented[1] nylon 6,6, so in order to compete, other companies (particularly the German BASF) developed the homopolymer nylon 6, or polycaprolactam — not a condensation polymer, but formed by a ring-opening polymerization (alternatively made by polymerizing aminocaproic acid). The peptide bond within the caprolactam is broken with the exposed active groups on each side being incorporated into two new bonds as the monomer becomes part of the polymer backbone. In this case, all amide bonds lie in the same direction, but the properties of nylon 6 are sometimes indistinguishable from those of nylon 6,6 — except for melt temperature and some fiber properties in products like carpets and textiles. There is also nylon 9. The 428 °F (220 °C) melting point of nylon 6 is lower than the 509 °F (265 °C) melting point of nylon 6,6.[2] Nylon 5,10, made from pentamethylene diamine and sebacic acid, was studied by Carothers even before nylon 6,6 and has superior properties, but is more expensive to make. In keeping with this naming convention, "nylon 6,12" (N-6,12) or "PA-6,12" is a copolymer of a 6C diamine and a 12C diacid. Similarly for N-5,10 N-6,11; N-10,12, etc. Other nylons include copolymerized dicarboxylic acid/diamine products that are not based upon the monomers listed above. For example, some aromatic nylons are polymerized with the addition of diacids like terephthalic acid (→ Kevlar, Twaron) or isophthalic acid (→ Nomex), more commonly associated with polyesters. There are copolymers of N-6,6/N6; copolymers of N-6,6/N-6/N-12; and others. Because of the way polyamides are formed, nylon would seem to be limited to unbranched, straight chains. But "star" branched nylon can be produced by the condensation of dicarboxylic acids with polyamines having three or more amino groups. The general reaction is: A molecule of water is given off and the nylon is formed. Its properties are determined by the R and R' groups in the monomers. In nylon 6,6, R = 4C and R' = 6C alkanes, but one also has to include the two carboxyl carbons in the diacid to get the number it donates to the chain. In Kevlar, both R and R' are benzene rings. Concepts of nylon production The first approach: combining molecules with an acid (COOH) group on each end are reacted with two chemicals that contain amine (NH2) groups on each end. This process creates nylon 6,6, made of hexamethylene diamine with six carbon atoms and adipic acid. The second approach: a compound has an acid at one end and an amine at the other and is polymerized to form a chain with repeating units of (-NH-[CH2]n-CO-)x. In other words, nylon 6 is made from a single six-carbon substance called caprolactam. In this equation, if n = 5, then nylon 6 is the assigned name (may also be referred to as polymer). The characteristic features of nylon 6,6 include: Pleats and creases can be heat-set at higher temperatures More compact molecular structure Better weathering properties; better sunlight resistance Softer "Hand" Higher melting point (256 °C/492.8 °F) Superior colorfastness Excellent abrasion resistance On the other hand, nylon 6 is easy to dye, more readily fades; it has a higher impact resistance, a more rapid moisture absorption, greater elasticity and elastic recovery.