Supstitucija (hemija)

U supstitucionim reakcijama, funkcionalna grupa jednog hemijskog jedinjenja se zamenjuje drugom grupom. U organskoj hemiji, reakcije elektrofilne i nukleofilne supstitucije imaju primarni značaj. Reakcije organske supstitucije se klasifikuju u nekoliko glavnih tipova organskih reakcija u zavisnosti od toga da li je reagens elektrofil ili nukleofil, da li je reakcioni intermedijar karbokatjon, karbanjon ili slobodni radikal, ili da li je supstrat alifatičan ili aromatičan. Detaljno razumevanje tipa reakcije pomaže u predviđanju produkta reakcije. To je takođe korisno za optimizaciju reakcije u pogledu promenljivih, kao što su temperatura i izvor rastvarača.

Dobar primer reakcije supstitucije je fotohemijska hlorinacija metana kojom se formira metil hlorid. When chlorine gas (Cl₂) is irradiated, some of the molecules are split into two chlorine radicals (Cl•), whose free electrons are strongly nucleophilic. One of them breaks a C–H covalent bond in CH₄ and grabs the hydrogen atom to form the electrically neutral HCl. The other radical reforms a covalent bond with the CH₃• to form CH₃Cl (methyl chloride).

hlorinacija metana hlorom

Nukleofilna supstitucija

Glavni članak: Nukleofilna supstitucija

Nukleofilna supstitucija se odvija kad je reagens nukleofil (atom ili molekul sa slobodnim elektronima). Nukleofil reaguje sa alifatičnim supstratom u reakciji nukleofilne alifatične supstitucija. Ta supstitucija se može odvijati putem dva različita mehanizma: unimolekularna nukleofilna supstitucija (SN₁) i bimolekularna nukleofilna supstitucija (SN₂). SN₁ mehanizam ima dva stupnja. U prvom stupnju, odlazeća grupa se udalji, čime se formira karbokatjon. U drugom stupnju, nukleofilni reagens napada karbokatjon i formira sigma vezu. Ovaj mehanizam može da proizvede bilo inverziju ili zadržavanje konfiguracije. SN₂ reakcija ima samo jedan stupanj. Napad reagensa i uklanjanje odlazeće grupe se odvijaju istovremeno. Ovaj mehanizam uvek dovodi do inverzije konfiguracije.

Kad je supstrat aromatično jedinjenje reakcioni tip je nukleofilna aromatična supstitucija. Derivati karboksilnih kiselina reaguju sa nukleofilima u nukleofilnoj acilnoj supstituciji.

The most general form for the reaction may be given as

Nuc: + R-LG → R-Nuc + LG:

where R-LG indicates the substrate. The electron pair (:) from the nucleophile (Nuc:) attacks the substrate (R-LG), forming a new covalent bond Nuc-R-LG. The prior state of charge is restored when the leaving group (LG) departs with an electron pair. The principal product in this case is R-Nuc. In such reactions, the nucleophile is usually electrically neutral or negatively charged, whereas the substrate is typically neutral or positively charged.

An example of nucleophilic substitution is the hydrolysis of an alkyl bromide, R-Br, under basic conditions, where the attacking nucleophile is the base OH⁻ and the leaving group is Br⁻:

R-Br + OH⁻ → R-OH + Br⁻

Nucleophilic substitution reactions are commonplace in organic chemistry, and they can be broadly categorized as taking place at a carbon of a saturated aliphatic compound carbon or (less often) at an aromatic or other unsaturated carbon center.

Mehanizmi

Glavni članci: SN1 reaction, SN2 reaction i Nucleophilic aromatic substitution

Nucleophilic substitutions on aliphatic carbon centers can proceed by two different mechanisms, unimolecular nucleophilic substitution (S_N1) and bimolecular nucleophilic substitution (S_N2).

The S_N1 mechanism has two steps. In the first step, the leaving group departs, forming a carbocation C⁺. In the second step, the nucleophilic reagent (Nuc:) attaches to the carbocation and forms a covalent sigma bond. If the substrate has a chiral carbon, this mechanism can result in either inversion of the stereochemistry or retention of configuration. Usually, both occur without preference. The result is racemization.

The S_N2 mechanism has just one step. The attack of the reagent and the expulsion of the leaving group happen simultaneously. This mechanism always results in inversion of configuration. If the substrate that is under nucleophilic attack is chiral, the reaction will therefore lead to an inversion of its stereochemistry, called a Walden inversion.

S_N2 attack may occur if the backside route of attack is not sterically hindered by substituents on the substrate. Therefore, this mechanism usually occurs at an unhindered primary carbon center. If there is steric crowding on the substrate near the leaving group, such as at a tertiary carbon center, the substitution will involve an S_N1 rather than an S_N2 mechanism; an S_N1 would also be more likely in this case because a sufficiently stable carbocation intermediary could be formed.

When the substrate is an aromatic compound, the reaction type is nucleophilic aromatic substitution, which occur with various mechanisms. Carboxylic acid derivatives react with nucleophiles in nucleophilic acyl substitution. This kind of reaction can be useful in preparing compounds.

Elektrofilna supstitucija

Glavni članak: Elektrofilna supstitucija

Elektrofili učestvuju u reakcijama elektrofilne supstitucije, a posebno u elektrofilnim aromatičnim supstitucijama.

Elektrofilna aromatična supstitucija

Elektrofilne reakcije sa drugim nezasićenim jedinjenjima, osim arena, generalno dovode do elektrofilne adicije umesto supstitucije.

Radical substitution

A radical substitution reaction involves radicals. An example is the Hunsdiecker reaction.

Organometallic substitution

Coupling reactions are a class of metal-catalyzed reactions involving an organometallic compound RM and an organic halide R′X that together react to form a compound of the type R-R′ with formation of a new carbon–carbon bond. Examples include the Heck reaction, Ullmann reaction, and Wurtz–Fittig reaction. Many variations exist.

Substituted compounds

Substituted compounds are chemical compounds where one or more hydrogen atoms of a core structure have been replaced with a functional group like alkyl, hydroxy, or halogen, or with larger substituent groups.

For example, benzene is a simple aromatic ring. Benzenes that have undergone substitution are a heterogeneous group of chemicals with a wide spectrum of uses and properties:

Examples of substituted benzene compounds
compound	general formula	general structure
Benzene	C6H6
Toluene	C6H5-CH3
o-Xylene	C6H4(-CH3)2
Mesitylene	C6H3(-CH3)3
Phenol	C6H5-OH

Vidi još

• Hel-Volhard-Zelinski halogenacija
• Fridel-Kraftsove reakcije

Literatura

• R. A. Rossi, R. H. de Rossi, Aromatic Substitution by the S_RN1 Mechanism, ACS Monograph Series No. 178, American Chemical Society, 1983. ISBN 0-8412-0648-1
• L. G. Wade, Organic Chemistry, 5th ed., Prentice Hall, Upper Saddle River, New Jersey, 2003.
• S. R. Hartshorn, Aliphatic Nucleophilic Substitution, Cambridge University Press, London, 1973. ISBN 0-521-09801-7
• Introducing Aliphatic Substitution with a Discovery Experiment Using Competing Electrophiles Timothy P. Curran, Amelia J. Mostovoy, Margaret E. Curran, and Clara Berger Journal of Chemical Education 2016 93 (4), 757-761 doi:10.1021/acs.jchemed.5b00394
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• Davis, F. A.; Kumar, A.; Chen, B. C. (1991). „Chemistry of oxaziridines. 16. A short, highly enantioselective synthesis of the AB-ring segments of γ-rhodomycionone and α-citromycinone using (+)-[(8,8-dimethoxycamphoryl)sulfonyl]oxaziridine”. J. Org. Chem. 56 (3): 1143—1145. doi:10.1021/jo00003a042. 
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• Bella M, Kobbelgaard S, Jørgensen KA (март 2005). „Organocatalytic regio- and asymmetric C-selective S(N)Ar reactions-stereoselective synthesis of optically active spiro-pyrrolidone-3,3'-oxoindoles”. Journal of the American Chemical Society. 127 (11): 3670—1. PMID 15771481. doi:10.1021/ja050200g. CS1 одржавање: Формат датума (веза)

Спољашње везе

• „Nucleophiles and Electrophiles”. butane.chem.uiuc.edu. Приступљено 2020-09-21. 
• „Electrophile | chemistry”. Encyclopedia Britannica (на језику: енглески). Приступљено 2020-09-21. 
• Aromatic Substitution Reactions – MSU