Origin of diastereofacial selectivity in tertiary 2-adamantyl cations.

The intrinsic factors governing the diastereofacial selectivity of 2-methyl-5-X-2-adamantyl cations (X = F (I(F)), Si(CH(3))(3) (I(Si))) toward a representative nucleophile, i.e., methanol, have been investigated in the gas phase at 750 Torr and in the 20-80 degrees C temperature range. The kinetic results indicate that CH(3)OH addition to I(F) proceeds through tight transition structures (TS(F)(syn) and TS(F)(anti)) characterized by advanced C-O bonding. The same interactions are much less pronounced in the comparatively loose transition structures involved in the CH(3)OH addition to I(Si) (TS(Si)(syn) and TS(Si)(anti)). The experimental evidence indicates that the activation barriers for the anti addition to I(F) and I(Si) are invariably lower than those for the syn attack. Large adverse entropic factors account for the preferred syn diastereoselectivity observed in the reaction with I(F). Entropy plays a minor role in the much looser transition structures involved in the reaction with I(Si), which instead exhibits a preferred anti diastereoselectivity. Comparison of the above gas-phase results with related theoretical and solution data suggests that the diastereofacial selectivity of I(F) and I(Si) measured in solution arises in part from the differential solvation of the two faces of the pyramidalized ions.     

Modeling a halogen dance reaction mechanism: A density functional theory study

Since the discovery of the halogen dance (HD) reaction more than 60 years ago, numerous insights into the mechanism have been unveiled. To date however, the reaction has not been investigated from a theoretical perspective. Density functional theory (DFT) was used to model the potential energy surface linking the starting reagents to the lithiated products for each step in the mechanism using a thiophene substrate. It was found that the lithium‐halogen exchange mechanism is critical to understand the HD mechanism in detail and yielded the knowledge that S_N2 transition states (TS) are favored over the four‐center type for the lithium‐bromine exchange steps. The overall driving force for the HD is thermodynamics, while the kinetic factors tightly control the reaction path through temperature. The S_N2 lithium‐bromide TS are barrierless, except the second, which is the limiting step. Finally, the model for the HD is discovered to be a pseudo‐clock type, due to a highly favorable bromide catalysis step and the reformation of 2‐bromothiophene. © 2016 Wiley Periodicals, Inc.     

A theoretical study on the mechanism of the addition reaction between carbene and epoxyethane

The mechanism of addition reaction between carbene and epoxyethane has been investigated employing the MP2 and B3LYP/6-311+G* levels of theory. Geometry optimization, vibrational analysis, and energy property for the involved stationary points on the potential energy surface have been calculated. Based on the calculated results at the MP2/6-311+G* level of theory, it can be predicted that there are two reaction mechanisms (1) and (2). In the first reaction carbene attacks the atom O of epoxyethane to form an intermediate 1a (IM1a), which is a barrier-free exothermic reaction. Then, IM1a can isomerize to IM1b via a transition state 1a (TS1a), where the potential barrier is 48.6 kJ/mol. Subsequently, IM1b isomerizes to a product epoxypropane (Pro1) via TS1b with a potential barrier of 14.2 kJ/mol. In the second carbene attacks the atom C of epoxyethane firstly to form IM2 via TS2a. Then IM2 isomerizes to a product allyl alcohol (Pro2) via TS2b with a potential barrier of 101.6 kJ/mol. Correspondingly, the reaction energies for the reactions (1) and (2) are −448.4 and −501.6 kJ/mol, respectively. Additionally, the orbital interactions are also discussed for the leading intermediate. The results based on the B3LYP/6-311+G* level of theory are paralleled to those on the MP2/6-311+G* level of theory. Furthermore, the halogen and methyl substituent effects of H₂C: on the two reaction mechanisms have been investigated. The calculated results indicate that the introductions of halogen or methyl make the addition reaction difficult to proceed.     

Diasteroselective synthesis of new spiropiperidine scaffolds from the CN(R,S) building block

A methodology allowing the construction of spiropiperidine scaffolds similar to those found in naturally occurring alkaloids has been developed. This approach begins with the well-established CN(R,S) strategy, the spiro-center being built by way of an intramolecular attack of a nitrile function by an organolithium species obtained by a halogen/lithium exchange reaction mediated by either t-BuLi or lithium naphthalenide.     

Retro-Diels-Alder reaction of 4H-1,2-benzoxazines to generate o-quinone methides: involvement of highly polarized transition states

Here, we describe mechanistic studies of the retro-Diels-Alder reaction of 4H-1,2-benzoxazines bearing various substituents on the benzene ring. 4H-1,2-Benzoxazines are very simple, but quite new, heterocyclic compounds that afford substituted o-quinone methides (o-QMs) through retro-Diels-Alder reaction under mild thermal conditions. The resultant o-QMs undergo Diels-Alder reaction in situ with dienophiles to give phenol and chroman derivatives. The mechanism of the generation of o-QMs has been little studied. Our experimental and density functional theory (DFT) studies have yielded the following results. (1) The generation of o-QMs, i.e., the retro-hetero-Diels-Alder reaction of 4H-1,2-benzoxazines, is rate determining, rather than the subsequent Diels-Alder reaction of the resultant o-QM with dienophiles. (2) The reaction rate is strongly influenced by the electronic features of substituents and the polarity of the solvent. The reaction proceeds faster in a polar solvent such as dimethyl sulfoxide, probably because of stabilization of the electronically polarized TS structure. (3) The reactions show characteristic positional effects of substitution on the benzene ring. While an electron-withdrawing group such as CF3 at C5, C6, or C7 positions decelerates the reaction, the same substituent at C8 accelerates the reaction, compared with the reaction of unsubstituted 4H-1,2-benzoxazine. In particular, substitution at C5 significantly decelerates the reaction as compared with the unsubstituted case. This is due to the difference in the inductive effect of CF3 at the different positions. Similar positional effects occur with a halogen (Cl) and a nitro group. All these data support the involvement of polarized TS structures, in which the O-N bond cleavage precedes the C-C bond cleavage.     

Heterogeneous reactions : VII. Further studies on the heterogeneous gas/solid reactions of solid alkoxide bases with vaporized chloromethyldimethylhalosilanes

The results of the heterogeneous gas/solid reactions of chloromethyldimethylchloro (and fluoro)silane with solid lithium, sodium and potassium methoxide in the temperature range from 80–160°C are presented and discussed. Reaction with lithium methoxide serves as a clean, efficient high yield synthesis of chloromethyldimethylmethoxysilane without the complicating factors of side products or solvent to separate. The reactions of both the sodium and potassium methoxides lead to the displacement of halogen from silicon and to the displacement of the chloromethyl group. New evidence for the mechanism of the latter reaction is presented. With the potassium compound methylethyldimethoxysilane also is formed and carbene, sila-olefin addition mechanism is suggested. Surprisingly, lithium t-buthoxide did not react with the chlorosilane but did react with the fluorosilane to produce chloromethyldimethyl-t-butoxysilane in high purity and excellent yield. The reaction with potassium t-butoxide was more complicated, giving substitution for halogen and the chloromethyl group at silicon as well as t-butyl ether.     

Electronic structure analysis of the oxygen-activation mechanism by Fe(II)- and α-ketoglutarate (αKG)-dependent dioxygenases

α-Ketoglutarate (αKG)-dependent nonheme iron enzymes utilize a high-spin (HS) ferrous center to couple the activation of oxygen to the decarboxylation of the cosubstrate αKG to yield succinate and CO(2), and to generate a high-valent ferryl species that then acts as an oxidant to functionalize the target C-H bond. Herein a detailed analysis of the electronic-structure changes that occur in the oxygen activation by this enzyme was performed. The rate-limiting step, which is identical on the septet and quintet surfaces, is the nucleophilic attack of the distal O atom of the O(2) adduct on the carbonyl group in αKG through a bicyclic transition state ((5, 7) TS1). Due to the different electronic structures in (5, 7) TS1, the decay of (7)TS1 leads to a ferric oxyl species, which undergoes a rapid intersystem crossing to form the ferryl intermediate. By contrast, a HS ferrous center ligated by a peroxosuccinate is obtained on the quintet surface following (5)TS1. Thus, additional two single-electron transfer steps are required to afford the same Fe(IV)-oxo species. However, the triplet reaction channel is catalytically irrelevant. The biological role of αKG played in the oxygen-activation reaction is dual. The αKG LUMO (C=O π*) serves as an electron acceptor for the nucleophilic attack of the superoxide monoanion. On the other hand, the αKG HOMO (C1-C2 σ) provides the second and third electrons for the further reduction of the superoxide. In addition to density functional theory, high-level ab initio calculations have been used to calculate the accurate energies of the critical points on the alternative potential-energy surfaces. Overall, the results delivered by the ab initio calculations are largely parallel to those obtained with the B3LYP density functional, thus lending credence to our conclusions.     

A DFT investigation of the addition reaction of monomeric lithium enolate derived from propiophenone to propene oxide: examination of the possible transition structures

The addition reaction of monomeric lithium enolate (Z)-1, derived from propiophenone, to propene oxide 2, was examined to clarify the exact geometry of the transition state (TS) involved in this type of reaction. The eight possible TSs and the corresponding pathways, four leading to syn gamma-hydroxy ketone (gamma-HK) 3 and four leading to anti gamma-HK 4, were compared, using the B3LYP/6-31+G(d)//B3LYP/6-31+G(d) theory level in vacuo and in the presence of the reaction solvent (toluene/hexane). In every case, the favored pathway involves a TS where the enolate C=C and the epoxide C-C are in a gauche relationship and where the Li(+) is stabilized by some C-C and C-H sigma bonds of epoxide 2.     

Cross-coupling reaction of alpha-chloroketones and organotin enolates catalyzed by zinc halides for synthesis of gamma-diketones

The reaction of tin enolates 1 with alpha-chloro- or bromoketones 2 gave gamma-diketones (1,4-diketones) 3 catalyzed by zinc halides. In contrast to the exclusive formation of 1,4-diketones 3 under catalytic conditions, uncatalyzed reaction of 1 with 2 gave aldol-type products 4 through carbonyl attack. NMR study indicates that the catalyzed reaction includes precondensation between tin enolates and alpha-haloketones providing an aldol-type species and their rearrangement of the oxoalkyl group with leaving halogen to produce 1,4-diketones. The catalyst, zinc halides, plays an important role in each step. The carbonyl attack for precondensation is accelerated by the catalyst as Lewis acid and the intermediate zincate promotes the rearrangement by releasing oxygen and bonding with halogen. Various types of tin enolates and alpha-chloro- and bromoketones were applied to the zinc-catalyzed cross-coupling. On the other hand, the allylic halides, which have no carbonyl moiety, were inert to the zinc-catalyzed coupling with tin enolates. The copper halides showed high catalytic activity for the coupling between tin enolates 1 and organic halides 7 to give gamma,delta-unsaturated ketones 8 and/or 9. The reaction with even chlorides proceeded effectively by the catalytic system.     

Interplay between halogen bond and lithium bond in MCN-LiCN-XCCH (M = H, Li, and Na; X = Cl, Br, and I) complex: the enhancement of halogen bond by a lithium bond

Quantum chemical calculations have been performed to study the complex of MCN-LiCN-XCCH (M = H, Li, and Na; X = Cl, Br, and I). The aim is to study the cooperative effect between halogen bond and lithium bond. The alkali metal has an enhancing effect on the lithium bond, making it increased by 77 and 94% for the Li and Na, respectively. There is the cooperativity between the lithium bond and halogen bond. The former has a larger enhancing effect on the latter, being in a range of 11.7-29.4%. The effect of cooperativity on the halogen bond is dependent on the type of metal and halogen atoms. The enhancing mechanism has been analyzed in views with the orbital interaction, charge transfer, dipole moment, polarizability, atom charges, and electrostatic potentials. The results show that the electrostatic interaction plays an important role in the enhancement of halogen bond.     

Electronic Structure Analysis of the Oxygen‐Activation Mechanism by FeII‐ and α‐Ketoglutarate (αKG)‐Dependent Dioxygenases

α‐Ketoglutarate (αKG)‐dependent nonheme iron enzymes utilize a high‐spin (HS) ferrous center to couple the activation of oxygen to the decarboxylation of the cosubstrate αKG to yield succinate and CO₂, and to generate a high‐valent ferryl species that then acts as an oxidant to functionalize the target C? H bond. Herein a detailed analysis of the electronic‐structure changes that occur in the oxygen activation by this enzyme was performed. The rate‐limiting step, which is identical on the septet and quintet surfaces, is the nucleophilic attack of the distal O atom of the O₂ adduct on the carbonyl group in αKG through a bicyclic transition state (^{5, 7}TS1). Due to the different electronic structures in ^{5, 7}TS1, the decay of ⁷TS1 leads to a ferric oxyl species, which undergoes a rapid intersystem crossing to form the ferryl intermediate. By contrast, a HS ferrous center ligated by a peroxosuccinate is obtained on the quintet surface following ⁵TS1. Thus, additional two single‐electron transfer steps are required to afford the same Fe^IV–oxo species. However, the triplet reaction channel is catalytically irrelevant. The biological role of αKG played in the oxygen‐activation reaction is dual. The αKG LUMO (C?O π*) serves as an electron acceptor for the nucleophilic attack of the superoxide monoanion. On the other hand, the αKG HOMO (C1? C2 σ) provides the second and third electrons for the further reduction of the superoxide. In addition to density functional theory, high‐level ab initio calculations have been used to calculate the accurate energies of the critical points on the alternative potential‐energy surfaces. Overall, the results delivered by the ab initio calculations are largely parallel to those obtained with the B3LYP density functional, thus lending credence to our conclusions.     

Rational Modification of the Hierarchy of Intermolecular Interactions in Molecular Crystal Structures by Using Tunable Halogen Bonds

A family of 16 isomolecular salts (3‐XpyH)₂[MX′₄] (3‐XpyH=3‐halopyridinium; M=Co, Zn; X=(F), Cl, Br, (I); X′=Cl, Br, I) each containing rigid organic cations and tetrahedral halometallate anions has been prepared and characterized by X‐ray single crystal and/or powder diffraction. Their crystal structures reflect the competition and cooperation between non‐covalent interactions: N? H???X′? M hydrogen bonds, C? X???X′? M halogen bonds and π–π stacking. The latter are essentially unchanged in strength across the series, but both halogen bonds and hydrogen bonds are modified in strength upon changing the halogens involved. Changing the organic halogen (X) from F to I strengthens the C? X???X′? M halogen bonds, whereas an analogous change of the inorganic halogen (X′) weakens both halogen bonds and N? H???X′? M hydrogen bonds. By so tuning the strength of the putative halogen bonds from repulsive to weak to moderately strong attractive interactions, the hierarchy of the interactions has been modified rationally leading to systematic changes in crystal packing. Three classes of crystal structure are obtained. In type A (C? F???X′? M) halogen bonds are absent. The structure is directed by N? H???X′? M hydrogen bonds and π‐stacking interactions. In type B structures, involving small organic halogens (X) and large inorganic halogens (X′), long (weak) C? X???X′? M interactions are observed with type I halogen–halogen interaction geometries (C? X???X′ ≈ X???X′? M ≈155°), but hydrogen bonds still dominate. Thus, minor but quite significant perturbations from the type A structure arise. In type C, involving larger organic halogens (X) and smaller inorganic halogens (X′), stronger halogen bonds are formed with a type II halogen–halogen interaction geometry (C? X???X′ ≈180°; X???X′? M ≈110°) that is electrostatically attractive. The halogen bonds play a major role alongside hydrogen bonds in directing the type C structures, which as a result are quite different from type A and B.     

Theoretical study of halophilic reactions of stable silylenes with chloro- and bromocarbons

A theoretical study of the mechanism of the reaction of stable silylenes with halocarbons has been carried out using the B3LYP density functional method. The main findings are as follows: (1) Lewis acid-base complexes formed between silylenes and halocarbons do not play a role in silylene insertion chemistry into halocarbons; therefore, the acid-base complex mechanism proposed by West et al. (J. Am. Chem. Soc. 2002, 124, 4186) is not appropriate to describe the disilane formation reaction. (2) The disilane formation reactions follow the energetically favorable general reaction pathway (X = halogen): (i) Y2Si: + HCX3 --> TS1 --> Y2XSi-CHX2. (ii) Y2Si: + Y2XSi-CHX2 --> TS2 --> Y2XSi-SiY2CHX2. (3) The observed preference of stable silylenes to undergo C-X bond insertion rather than C-H bond has been investigated. The theoretical findings suggest that this preference is a result of the thermodynamic factor. (4) Stable silylenes prefer to insert into a C-Br rather than a C-Cl bond because the energy barrier to insertion is lower, and the reaction is more exothermic.     

Determining the transition-state structure for different SN2 reactions using experimental nucleophile carbon and secondary alpha-deuterium kinetic isotope effects and theory

Nucleophile (11)C/ (14)C [ k (11)/ k (14)] and secondary alpha-deuterium [( k H/ k D) alpha] kinetic isotope effects (KIEs) were measured for the S N2 reactions between tetrabutylammonium cyanide and ethyl iodide, bromide, chloride, and tosylate in anhydrous DMSO at 20 degrees C to determine whether these isotope effects can be used to determine the structure of S N2 transition states. Interpreting the experimental KIEs in the usual fashion (i.e., that a smaller nucleophile KIE indicates the Nu-C alpha transition state bond is shorter and a smaller ( k H/ k D) alpha is found when the Nu-LG distance in the transition state is shorter) suggests that the transition state is tighter with a slightly shorter NC-C alpha bond and a much shorter C alpha-LG bond when the substrate has a poorer halogen leaving group. Theoretical calculations at the B3LYP/aug-cc-pVDZ level of theory support this conclusion. The results show that the experimental nucleophile (11)C/ (14)C KIEs can be used to determine transition-state structure in different reactions and that the usual method of interpreting these KIEs is correct. The magnitude of the experimental secondary alpha-deuterium KIE is related to the nucleophile-leaving group distance in the S N2 transition state ( R TS) for reactions with a halogen leaving group. Unfortunately, the calculated and experimental ( k H/ k D) alpha's change oppositely with leaving group ability. However, the calculated ( k H/ k D) alpha's duplicate both the trend in the KIE with leaving group ability and the magnitude of the ( k H/ k D) alpha's for the ethyl halide reactions when different scale factors are used for the high and the low energy vibrations. This suggests it is critical that different scaling factors for the low and high energy vibrations be used if one wishes to duplicate experimental ( k H/ k D) alpha's. Finally, neither the experimental nor the theoretical secondary alpha-deuterium KIEs for the ethyl tosylate reaction fit the trend found for the reactions with a halogen leaving group. This presumably is found because of the bulky (sterically hindered) leaving group in the tosylate reaction. From every prospective, the tosylate reaction is too different from the halogen reactions to be compared.     

High level ab initio exploration on the conversion of carbon dioxide into oxazolidinones: the mechanism and regioselectivity

Density functional theory (DFT) and second order M?ller-Plesset perturbation (MP2) calculations, employing the 6-311++G(d,p) basis set, were carried out on alkyl-substituted aziridines to explore the reaction mechanisms and regioselectivity associated with their ring-opening conversions to oxazolidinones, in the presence of carbon dioxide. Computational results, employing the self-consistent reaction field polarizable continuum model (SCRF(PCM/Bader)), indicated that the conversions proceed with thermodynamic ease in THF solvent at room temperature. It is proposed that the N-alkylaziridine promotes ring opening through a SN2 attack of the iodide ion, of catalytic lithium iodide, on the preformed complex. The oxazolidinone regioisomer ratio is highly sensitive to aziridine ring-carbon substitution. Therein, monophenyl substitutions show preference to opening more highly substituted carbon-nitrogen bonds, providing rationale as to why experimental works result in an exclusive oxazolidinone regioisomer product.     

Concerning the mechanism of the ring opening of propylene oxide in the copolymerization of propylene oxide and carbon dioxide to give poly(propylene carbonate)

The reactions between (TPP)AlX, where TPP = tetraphenylporphyrin and X = Cl, O(CH(2))(9)CH(3), and O(2)C(CH(2))(6)CH(3), and propylene oxide, PO, have been studied in CDCl(3) and have been shown to give (TPP)AlOCHMeCH(2)X and (TPP)AlOCH(2)CHMeX compounds. The relative rates of ring opening of PO follow the order Cl > OR > O(2)CR, but in the presence of added 4-(dimethylamino)pyridine, DMAP (1 equiv), the order is changed to O(2)CR > OR. From studies of kinetics, the ring opening of PO is shown to be first order in [Al]. Carbon dioxide inserts reversibly into the Al-OR bond to give the compound (TPP)AlO(2)COR, and this reaction is promoted by the addition of DMAP. The coordination of DMAP to (TPP)AlX is favored in the order O(2)C(CH(2))(6)CH(3) > O(2)CO(CH(2))(9)CH(3) > O(CH(2))(9)CH(3). The microstructure of the poly(propylene carbonate), PPC, formed in the reactions between (TPP)AlCl/DMAP and (R,R-salen)CrCl and rac-PO/S-PO/R-PO and CO(2), has been investigated by (13)C [(1)H] NMR spectroscopy. The ring opening of PO is shown to proceed via competitive attack on the methine and methylene carbon atoms, and furthermore attack at the methine carbon occurs with both retention and inversion of stereochemistry. On the basis of these results, the reaction pathway leading to ring opening of PO can be traced to an interchange associative mechanism, wherein coordination of PO to the electrophilic aluminum atom occurs within the vicinity of the Al-X bond (X = Cl, OR, O(2)CR, or O(2)COR). The role of DMAP is two-fold: (i) to labilize the trans Al-X bond toward heterolytic behavior, and (ii) to promote the insertion of CO(2) into the Al-OR bond.     

Nucleophilic addition to a p-benzyne derived from an enediyne: a new mechanism for halide incorporation into biomolecules

Biosynthesis of haloaromatics ordinarily occurs by electrophilic attack of an activated halogen species on an electron-rich aromatic ring. We now present the discovery of a new reaction whereby a nucleophilic halide anion can be attached even to an aromatic ring without activating substituents. We show that the enediyne cyclodeca-1,5-diyn-3-ene, in the presence of lithium halide and a weak acid, is converted to 1-halotetrahydronaphthalene. The kinetics are consistent with rate-limiting cyclization to a p-benzyne biradical that rapidly adds halide and is then protonated. This reaction has interesting mechanistic features and important implications for incorporation of halide into biomolecules.     

The importance of alkali cations in the [{RuCl2(p-cymene)}2]-pseudo-dipeptide-catalyzed enantioselective transfer hydrogenation of ketones

We studied the role of alkali cations in the [{RuCl2(p-cymene)}2]-pseudo-dipeptide-catalyzed enantioselective transfer hydrogenation of ketones with isopropanol. Lithium salts were shown to increase the enantioselectivity of the reaction when iPrONa or iPrOK was used as the base. Similar transfer-hydrogenation systems that employ chiral amino alcohol or monotosylated diamine ligands are not affected by the addition of lithium salts. These observations have led us to propose that an alternative reaction mechanism operates in pseudo-dipeptide-based systems, in which the alkali cation is an important player in the ligand-assisted hydrogen-transfer step. DFT calculations of the proposed transition-state (TS) models involving different cations (Li+, Na+, and K+) confirm a considerable loosening of the TS with larger cations. This loosening may be responsible for the fewer interactions between the substrate and the catalytic complex, leading to lower enantiodifferentiation. This mechanistic hypothesis has found additional experimental support; the low ee obtained with [BnNMe3]OH (a large cation) as base can be dramatically improved by introducing lithium cations into the system. Also, the complexation of Na+, K+, and Li+ cations by the addition of [15]crown-5 and [18]crown-6 ethers and cryptand 2.1.1 (which selectively bind to these cations and, thus, increase their bulkiness), respectively, to the reaction mixture led to a significant drop in the enantioselectivity of the reaction. The lithium effect has proved useful for enhancing the reduction of different aromatic and heteroaromatic ketones.     

Theoretical study on the reaction mechanism of the alcoholysis of isocyanates

In this paper, the reactions of HNCO or CH₃NCO with methanol have been studied using the ab initio MO method. The geometries of the reactants and products have been optimized by the energy gradient method. The calculated results are in accordance with experiment. Using Powell's method, by the minimization of the Euclidean norm σ of the gradient, the structures of the transition state (TS ) for the two reactions were obtained. The structures have been further confirmed as TS by finding that there is one and only one negative eigenvalue for their force constant matrix. The imaginary vibration mode corresponding to the TS was also discussed. The calculated activation barriers of these two reactions are 96.02 and 95.13 kJ/mol, respectively. It can be concluded that the alcoholysis reaction of isocyanate is a nucleophilic addition reaction with methanol as an electronic donor and isocyanate as an acceptor and that the hydroxyl hydrogen of CH₃OH plays an important role in the reaction.     

Triangular halogen trimers. A DFT study of the structure, cooperativity, and vibrational properties

Triangular halogen trimers (RX)3, where X = Br, I and R represents H, H3C, H2FC, HF2C, F3C, CH2=CH, CH[triple bond]C, and Ph, have been investigated using the density functional theory in the Perdew, Burke, and Ernzerhof method. We report herein the optimized geometries of the stable structures, their vibrational frequencies, and binding energies with the two- and three-body terms. All trimer structures possess a cyclic array of halogen atoms in the type II approach by virtue of the nonspherical atomic charge distribution around the halogens. The Br...Br interactions in trimers are very weak, whereas the I...I interactions in trimers are relatively stronger. While all bromine trimers and most of iodine trimers are predicted to be noncooperative, three of iodine trimers show weak cooperativity. The analysis of vibration modes reveals that all halogen trimers exhibit no especially remarkable frequency shifts. It is also shown that the electrostatic contribution plays a major role in the halogen...halogen interactions in halogen trimers. In contrast to bromine trimers, the relative contribution of charge-transfer component to the halogen...halogen interactions becomes more important for iodine trimers.